[go: up one dir, main page]
Skip to main content

Advertisement

SpringerLink
Log in

Molecular Mechanism of Novel PAMAM Dendrimer Decorated Tectona grandis and Lactobacillus plantarum Nanoparticles on Autophagy-Induced Apoptosis in TNBC Cells

  • Research
  • Published:
BioNanoScience Aims and scope Submit manuscript

Abstract

Triple-negative breast cancer presents a global health concern due to its prevalence and treatment challenges. The heterogeneity of tumor subtypes and the lack of therapeutic targets contribute to treatment failure, compounded by adverse effects and resistance to conventional treatments. Consequently, there is an urgent need for innovative therapeutic strategies. This study aims to develop a green-synthesized compound by conjugating Tectona grandis and Lactobacillus plantarum with PAMAM dendrimers, evaluating its efficacy against TNBC. The potent bioactive compounds identified, 1-naphthalenecarboxylicacid, -(3-furanyl) ethyl] decahydro-1,4a-didimethyl-6-methylene from T. grandis and 3-phenyl-1,2,4-benzotriazine from L. plantarum, were analyzed through GC-MS. Their interaction with the autophagy gene ATG5 was examined using the PyRX program, demonstrating potential for drug design. Characterization of the synthesized compounds was conducted through UV-Vis spectroscopy, TEM, DLS, Zeta Potential, and FTIR analysis, confirming the formation of negatively charged, polydispersed, multi-branched (5.71–7.54 nm) with an absorption peak at 351 nm nanoparticles (PDTgNP) and positively charged, monodispersed, multi-branched (11–17 nm), absorption peak at 258 nm nanoparticles (PDLpNP). The antitumor efficacy of PDTgNP and PDLpNP was evaluated through MTT assay, scratch assay, DAPI, and double-staining techniques on the MDA-MB-231 cell line, demonstrating dose-dependent cytotoxicity with IC50 values of 43.9 μg/ml and 54.90 µg/ml, respectively, along with its enhanced autophagic and apoptotic efficacy. Additionally, PDTgNP and PDLpNP downregulated LC3 while upregulating ATG3, ATG5, and ATG12 in MDA-MB-231 cells, indicating potential action of autophagy. Therefore, this green synthesis method holds promise as an effective approach, potentially yielding novel promising anticancer agents for the treatment of TNBC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17

Similar content being viewed by others

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

TNBC:

Triple-negative breast cancer

PAMAM:

Poly amido amine

T. grandis :

Tectona grandis

L. plantarum :

Lactobacillus plantarum

MRS broth:

De Man–Rogosa–Sharpe broth

PDTgNP:

PAMAM dendrimer decorated T. grandis nanoparticles

PDLpNP:

PAMAM dendrimer decorated L. plantarum nanoparticles

EPR:

Enhanced permeability and retention

METgF:

Methanolic extract of T. grandis flower

GC-MS:

Gas chromatography-mass spectrum

AMU:

Atomic mass units

EI:

Electron impact

TEM:

Transmission electron microscopy

DLS:

Dynamic light scattering

FTIR:

Fourier transform infrared spectrometer

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

RT-PCR:

Real-Time PCR

PDB:

Protein data bank

AO:

Acridine Orange

EtBr:

Ethidium Bromide

References

  1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660

  2. Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023). Cancer statistics, 2023. CA: A Cancer Journal for Clinicians, 73(1), 17–48. https://doi.org/10.3322/caac.21763

  3. Emran, T. B., Shahriar, A., Mahmud, A. R., Rahman, T., Abir, M. H., Siddiquee, M. F.-R., … & Hassan, M. M. (2022). Multidrug resistance in cancer: Understanding molecular mechanisms, immunoprevention and therapeutic approaches. Frontiers in Oncology, 12. https://doi.org/10.3389/fonc.2022.891652

  4. Mathew, R., Karantza-Wadsworth, V., & White, E. (2007). Role of autophagy in cancer. Nature Reviews Cancer, 7(12), 961–967. https://doi.org/10.1038/nrc2254

    Article  Google Scholar 

  5. Chen, H.-Y., Huang, T.-C., Shieh, T.-M., Wu, C.-H., Lin, L.-C., & Hsia, S.-M. (2017). Isoliquiritigenin induces autophagy and inhibits ovarian cancer cell growth. International Journal of Molecular Sciences, 18(10), 2025. https://doi.org/10.3390/ijms18102025

    Article  Google Scholar 

  6. Schmukler, E., Kloog, Y., & Pinkas-Kramarski, R. (2014). Ras and autophagy in cancer development and therapy. Oncotarget, 5(3), 577–586. https://doi.org/10.18632/oncotarget.1775

    Article  Google Scholar 

  7. Fan, H., He, Y., Xiang, J., Zhou, J., Wan, X., You, J., … & Lei, Y. (2022). ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy. Redox Biology, 53, 102339. https://doi.org/10.1016/j.redox.2022.102339

  8. Nie, G., Tang, B., Lv, M., Li, D., Li, T., Ou, R., … & Wen, J. (2023). HPV E6 promotes cell proliferation of cervical cancer cell by accelerating accumulation of RBM15 dependently of autophagy inhibition. Cell Biology International, 47(8), 1327–1343.

  9. Li, N., Zhang, X., Chen, J., Gao, S., Wang, L., & Zhao, Y. (2023). Perturbation of autophagy by a Beclin 1-targeting stapled peptide induces mitochondria stress and inhibits proliferation of pancreatic cancer cells. Cancers, 15(3), 953.

    Article  Google Scholar 

  10. Yu, B., Zhou, Y., & He, J. (2023). TRIM13 inhibits cell proliferation and induces autophagy in lung adenocarcinoma by regulating KEAP1/NRF2 pathway. Cell Cycle, 22(12), 1496–1513.

    Article  Google Scholar 

  11. Cavallaro, G., Sardo, C., Craparo, E. F., Porsio, B., & Giammona, G. (2017). Polymeric nanoparticles for siRNA delivery: Production and applications. International Journal of Pharmaceutics, 525(2), 313–333. https://doi.org/10.1016/j.ijpharm.2017.04.008

    Article  Google Scholar 

  12. Delplace, V., & Nicolas, J. (2015). Degradable vinyl polymers for biomedical applications. Nature Chemistry, 7(10), 771–784. https://doi.org/10.1038/nchem.2343

    Article  Google Scholar 

  13. George, A., Shah, P. A., & Shrivastav, P. S. (2019). Natural biodegradable polymers based nano-formulations for drug delivery: A review. International Journal of Pharmaceutics, 561, 244–264. https://doi.org/10.1016/j.ijpharm.2019.03.011

    Article  Google Scholar 

  14. Chauhan, A. (2018). Dendrimers for drug delivery. Molecules, 23(4), 938. https://doi.org/10.3390/molecules23040938

    Article  MathSciNet  Google Scholar 

  15. Ghaffari, M., Dehghan, G., Baradaran, B., Zarebkohan, A., Mansoori, B., Soleymani, J., … & Hamblin, M. R. (2020). Co-delivery of curcumin and Bcl-2 siRNA by PAMAM dendrimers for enhancement of the therapeutic efficacy in HeLa cancer cells. Colloids and Surfaces B: Biointerfaces, 188, 110762. https://doi.org/10.1016/j.colsurfb.2019.110762

  16. Chis, A. A., Dobrea, C., Morgovan, C., Arseniu, A. M., Rus, L. L., Butuca, A., … & Frum, A. (2020). Applications and limitations of dendrimers in biomedicine. Molecules, 25(17), 3982. https://doi.org/10.3390/molecules25173982

  17. Palmerston Mendes, L., Pan, J., & Torchilin, V. (2017). Dendrimers as nanocarriers for nucleic acid and drug delivery in cancer therapy. Molecules, 22(9), 1401. https://doi.org/10.3390/molecules22091401

    Article  Google Scholar 

  18. Ahmad, R., Srivastava, S., Ghosh, S., & Khare, S. K. (2021). Phytochemical delivery through nanocarriers: A review. Colloids and Surfaces B: Biointerfaces, 197, 111389. https://doi.org/10.1016/j.colsurfb.2020.111389

    Article  Google Scholar 

  19. Alven, S., & Aderibigbe, B. A. (2020). The therapeutic efficacy of dendrimer and micelle formulations for breast cancer treatment. Pharmaceutics, 12(12), 1212. https://doi.org/10.3390/pharmaceutics12121212

    Article  Google Scholar 

  20. Amreddy, N., Babu, A., Panneerselvam, J., Srivastava, A., Muralidharan, R., Chen, A., … & Ramesh, R. (2018). Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment. Nanomedicine: Nanotechnology, Biology and Medicine, 14(2), 373–384. https://doi.org/10.1016/j.nano.2017.11.010

  21. Carvalho, M. R., Reis, R. L., & Oliveira, J. M. (2020). Dendrimer nanoparticles for colorectal cancer applications. Journal of Materials Chemistry B, 8(6), 1128–1138. https://doi.org/10.1039/C9TB02289A

    Article  Google Scholar 

  22. Khalil, H. H., Osman, H. A., Teleb, M., Darwish, A. I., Abu-Serie, M. M., Khattab, S. N., & Haiba, N. S. (2021). Engineered s -triazine-based dendrimer-honokiol conjugates as targeted MMP-2/9 inhibitors for halting hepatocellular carcinoma. ChemMedChem, 16(24), 3701–3719. https://doi.org/10.1002/cmdc.202100465

    Article  Google Scholar 

  23. Lo, S.-T., Kumar, A., Hsieh, J.-T., & Sun, X. (2013). Dendrimer nanoscaffolds for potential theranostics of prostate cancer with a focus on radiochemistry. Molecular Pharmaceutics, 10(3), 793–812. https://doi.org/10.1021/mp3005325

    Article  Google Scholar 

  24. Zhou, X., Xu, X., Hu, Q., Wu, Y., Yu, F., He, C., … & Hu, H. (2023). Novel manganese and polyester dendrimer-based theranostic nanoparticles for MRI and breast cancer therapy. Journal of Materials Chemistry B, 11(3), 648–656.

  25. Sheikh, A., Abourehab, M. A. S., Tulbah, A. S., & Kesharwani, P. (2023). Aptamer-grafted, cell membrane-coated dendrimer loaded with doxorubicin as a targeted nanosystem against epithelial cellular adhesion molecule (EpCAM) for triple negative breast cancer therapy. Journal of Drug Delivery Science and Technology, 86, 104745.

    Article  Google Scholar 

  26. Yousefi, M., Narmani, A., & Jafari, S. M. (2020). Dendrimers as efficient nanocarriers for the protection and delivery of bioactive phytochemicals. Advances in Colloid and Interface Science, 278, 102125. https://doi.org/10.1016/j.cis.2020.102125

    Article  Google Scholar 

  27. Ramachandran, S., Rajasekaran, A., & Kumar, K. M. (2011). Antidiabetic, antihyperlipidemic and antioxidant potential of methanol extract of Tectona grandis flowers in streptozotocin induced diabetic rats. Asian Pacific Journal of Tropical Medicine, 4(8), 624–631. https://doi.org/10.1016/S1995-7645(11)60160-0

    Article  Google Scholar 

  28. Nalvothula, R., Nagati, V. B., Koyyati, R., Merugu, R., & Padigya, P. R. M. (2014). Biogenic synthesis of silver nanoparticles using Tectona grandis leaf extract and evaluation of their antibacterial potential. International Journal of ChemTech Research, 6(1), 293–298.

    Google Scholar 

  29. Ghareeb, M. A., Shoeb, H. A., Madkour, H. M. F., Refaey, L.A.-G., Mohamed, M.A.-M., & Saad, A. M. (2014). Antioxidant and cytotoxic activities of Tectona grandis Linn leaves. International Journal of Phytopharmacology, 5(2), 143–157.

    Google Scholar 

  30. Senthilkumar, N., Nandhakumar, E., Priya, P., Soni, D., Vimalan, M., & Vetha Potheher, I. (2017). Synthesis of ZnO nanoparticles using leaf extract of Tectona grandis (L.) and their anti-bacterial, anti-arthritic, anti-oxidant and in vitro cytotoxicity activities. New Journal of Chemistry, 41(18), 10347–10356. https://doi.org/10.1039/C7NJ02664A

    Article  Google Scholar 

  31. Eswari, K. M., Asaithambi, S., Karuppaiah, M., Sakthivel, P., Balaji, V., Ponelakkia, D. K., … & G, R. (2022). Green synthesis of ZnO nanoparticles using Abutilon indicum and Tectona grandis leaf extracts for evaluation of anti-diabetic, anti-inflammatory and in-vitro cytotoxicity activities. Ceramics International, 48(22), 33624–33634. https://doi.org/10.1016/j.ceramint.2022.07.308

  32. Younis, H. M., Hussein, H. A., Khaphi, F. L., & Saeed, Z. K. (2023). Green biosynthesis of silver and gold nanoparticles using teak (Tectona grandis) leaf extract and its anticancer and antimicrobial activity. Heliyon, 9(11), e21698. https://doi.org/10.1016/j.heliyon.2023.e21698

  33. Mohseni, A. H., Casolaro, V., Bermúdez-Humarán, L. G., Keyvani, H., & Taghinezhad-S, S. (2021). Modulation of the PI3K/Akt/mTOR signaling pathway by probiotics as a fruitful target for orchestrating the immune response. Gut Microbes, 13(1). https://doi.org/10.1080/19490976.2021.1886844

  34. Delgado, S., Sánchez, B., Margolles, A., Ruas-Madiedo, P., & Ruiz, L. (2020). Molecules produced by probiotics and intestinal microorganisms with immunomodulatory activity. Nutrients, 12(2), 391. https://doi.org/10.3390/nu12020391

    Article  Google Scholar 

  35. Luz, C., Calpe, J., Manuel Quiles, J., Torrijos, R., Vento, M., Gormaz, M., … & Meca, G. (2021). Probiotic characterization of Lactobacillus strains isolated from breast milk and employment for the elaboration of a fermented milk product. Journal of Functional Foods, 84, 104599. https://doi.org/10.1016/j.jff.2021.104599

  36. Jahanshahi, M., Maleki Dana, P., Badehnoosh, B., Asemi, Z., Hallajzadeh, J., Mansournia, M. A., & … Chaichian, S. (2020). Anti-tumor activities of probiotics in cervical cancer. Journal of Ovarian Research, 13(1), 68. https://doi.org/10.1186/s13048-020-00668-x

  37. Mego, M., Holec, V., Drgona, L., Hainova, K., Ciernikova, S., & Zajac, V. (2013). Probiotic bacteria in cancer patients undergoing chemotherapy and radiation therapy. Complementary Therapies in Medicine, 21(6), 712–723. https://doi.org/10.1016/j.ctim.2013.08.018

    Article  Google Scholar 

  38. Sun, M., Liu, W., Song, Y., Tuo, Y., Mu, G., & Ma, F. (2021). The effects of Lactobacillus plantarum-12 crude exopolysaccharides on the cell proliferation and apoptosis of human colon cancer (HT-29) cells. Probiotics and Antimicrobial Proteins, 13, 413–421.

    Article  Google Scholar 

  39. Yue, Y., Ye, K., Lu, J., Wang, X., Zhang, S., Liu, L., … & Pang, X. (2020). Probiotic strain Lactobacillus plantarum YYC-3 prevents colon cancer in mice by regulating the tumour microenvironment. Biomedicine & Pharmacotherapy, 127, 110159.

  40. Amin, M., Navidifar, T., Saeb, S., Barzegari, E., & Jamalan, M. (2023). Tumor-targeted induction of intrinsic apoptosis in colon cancer cells by Lactobacillus plantarum and Lactobacillus rhamnosus strains. Molecular Biology Reports, 50(6), 5345–5354.

    Article  Google Scholar 

  41. Yue, Y.-C., Yang, B.-Y., Lu, J., Zhang, S.-W., Liu, L., Nassar, K., … & Lv, J.-P. (2020). Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway. Microbial Cell Factories, 19, 1–12.

  42. Pathak, N., Singh, P., Singh, P. K., Sharma, S., Singh, R. P., Gupta, A., … & Tripathi, M. (2022). Biopolymeric nanoparticles based effective delivery of bioactive compounds toward the sustainable development of anticancerous therapeutics. Frontiers in Nutrition, 9. https://doi.org/10.3389/fnut.2022.963413

  43. ud Din, F., Aman, W., Ullah, I., Qureshi, O. S., Mustapha, O., Shafique, S., & Zeb, A. (2017). Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. International Journal of Nanomedicine, 12, 7291–7309.https://doi.org/10.2147/IJN.S146315

  44. Mittal, P., Saharan, A., Verma, R., Altalbawy, F. M. A., Alfaidi, M. A., Batiha, G. E.-S., … & Rahman, M. S. (2021). Dendrimers: A new race of pharmaceutical nanocarriers. BioMed Research International, 2021, 1–11. https://doi.org/10.1155/2021/8844030

  45. Hassanen, E. I., Ahmed, L. I., Fahim, K. M., Shehata, M. G., & Badr, A. N. (2023). Chitosan nanoparticle encapsulation increased the prophylactic efficacy of Lactobacillus plantarum RM1 against AFM1-induced hepatorenal toxicity in rats. Environmental Science and Pollution Research, 30(59), 123925–123938.

    Article  Google Scholar 

  46. Ganaie, H. A., & Ali, M. N. (2016). GC-MS analysis and evaluation of mutagenic and antimutagenic activity of ethyl acetate extract of Ajuga bracteosa Wall ex. Benth: An endemic medicinal plant of Kashmir Himalaya, India. Journal of Clinical Toxicology, 06(02). https://doi.org/10.4172/2161-0495.1000288

  47. Sentürk, M., Ercan, F., & Yalcin, S. (2020). The secondary metabolites produced by Lactobacillus plantarum downregulate BCL-2 and BUFFY genes on breast cancer cell line and model organism Drosophila melanogaster: Molecular docking approach. Cancer Chemotherapy and Pharmacology, 85(1), 33–45. https://doi.org/10.1007/s00280-019-03978-0

    Article  Google Scholar 

  48. Baliyan, S., Mukherjee, R., Priyadarshini, A., Vibhuti, A., Gupta, A., Pandey, R. P., & Chang, C.-M. (2022). Determination of antioxidants by DPPH radical scavenging activity and quantitative phytochemical analysis of Ficus religiosa. Molecules, 27(4), 1326. https://doi.org/10.3390/molecules27041326

    Article  Google Scholar 

  49. Abdelfatah, S., Berg, A., Böckers, M., & Efferth, T. (2019). A selective inhibitor of the Polo-box domain of Polo-like kinase 1 identified by virtual screening. Journal of Advanced Research, 16, 145–156. https://doi.org/10.1016/j.jare.2018.10.002

    Article  Google Scholar 

  50. Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221–234. https://doi.org/10.1007/s10822-013-9644-8

    Article  Google Scholar 

  51. Gürbüz, M. U., & Ertürk, A. S. (2018). Synthesis and characterization of Jeffamine core PAMAM Dendrimer-silver nanocomposites (Ag JCPDNCs) and their evaluation in the reduction of 4-nitrophenol. Journal of the Turkish Chemical Society Section A: Chemistry, 5(2), 885–894. https://doi.org/10.18596/jotcsa.428572

    Article  Google Scholar 

  52. Kaup, R., ten Hove, J. B., & Velders, A. H. (2021). Dendroids, discrete covalently cross-linked dendrimer superstructures. ACS Nano, 15(1), 1666–1674. https://doi.org/10.1021/acsnano.0c09322

    Article  Google Scholar 

  53. Wang, X., Guerrand, L., Wu, B., Li, X., Boldon, L., Chen, W.-R., & Liu, L. (2012). Characterizations of polyamidoamine dendrimers with scattering techniques. Polymers, 4(1), 600–616. https://doi.org/10.3390/polym4010600

    Article  Google Scholar 

  54. Dobrovolskaia, M. A., Patri, A. K., Simak, J., Hall, J. B., Semberova, J., De Paoli Lacerda, S. H., & McNeil, S. E. (2012). Nanoparticle size and surface charge determine effects of PAMAM dendrimers on human platelets in vitro. Molecular Pharmaceutics, 9(3), 382–393. https://doi.org/10.1021/mp200463e

    Article  Google Scholar 

  55. Lombardo, D., Calandra, P., Bellocco, E., Laganà, G., Barreca, D., Magazù, S., … & Kiselev, M. A. (2016). Effect of anionic and cationic polyamidoamine (PAMAM) dendrimers on a model lipid membrane. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1858(11), 2769–2777. https://doi.org/10.1016/j.bbamem.2016.08.001

  56. Rasmussen, M. K., Pedersen, J. N., & Marie, R. (2020). Size and surface charge characterization of nanoparticles with a salt gradient. Nature Communications, 11(1), 2337. https://doi.org/10.1038/s41467-020-15889-3

    Article  Google Scholar 

  57. Saleh, T. A., Al-Shalalfeh, M. M., & Al-Saadi, A. A. (2016). Graphene dendrimer-stabilized silver nanoparticles for detection of methimazole using Surface-enhanced Raman scattering with computational assignment. Scientific Reports, 6(1), 32185. https://doi.org/10.1038/srep32185

    Article  Google Scholar 

  58. Faisal, S., Tariq, M. H., Abdullah, Zafar, S., Un Nisa, Z., Ullah, R., … & Khan, R. U. (2024). Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles. Scientific Reports, 14(1), 7875.

  59. Sulaiman, G. M., Waheeb, H. M., Jabir, M. S., Khazaal, S. H., Dewir, Y. H., & Naidoo, Y. (2020). Hesperidin loaded on gold nanoparticles as a drug delivery system for a successful biocompatible, anti-cancer, anti-inflammatory and phagocytosis inducer model. Scientific Reports, 10(1), 9362.

    Article  Google Scholar 

  60. Lee, K. H., Khan, F. N., Cosby, L., Yang, G., & Winter, J. O. (2021). Polymer concentration maximizes encapsulation efficiency in electrohydrodynamic mixing nanoprecipitation. Frontiers in Nanotechnology, 3, 719710.

    Article  Google Scholar 

  61. Zhang, H.-W., Hu, J.-J., Fu, R.-Q., Liu, X., Zhang, Y.-H., Li, J., … & Gao, N. (2018). Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Scientific Reports, 8(1), 11255. https://doi.org/10.1038/s41598-018-29308-7

  62. Thomas, S., Gunasangkaran, G., Arumugam, V. A., & Muthukrishnan, S. (2022). Synthesis and characterization of zinc oxide nanoparticles of solanum nigrum and its anticancer activity via the induction of apoptosis in cervical cancer. Biological Trace Element Research, 200(6), 2684–2697. https://doi.org/10.1007/s12011-021-02898-6

    Article  Google Scholar 

  63. Shiao, W.-C., Kuo, C.-H., Tsai, Y.-H., Hsieh, S.-L., Kuan, A.-W., Hong, Y.-H., & Huang, C.-Y. (2020). In vitro evaluation of anti-colon cancer potential of crude extracts of fucoidan obtained from sargassum glaucescens pretreated by compressional-puffing. Applied Sciences, 10(9), 3058. https://doi.org/10.3390/app10093058

    Article  Google Scholar 

  64. Meng, X., & Shao, Z. (2022). Ambrosin exerts strong anticancer effects on human breast cancer cells via activation of caspase and inhibition of the Wnt/β-catenin pathway. Tropical Journal of Pharmaceutical Research, 20(4), 809–814. https://doi.org/10.4314/tjpr.v20i4.22

    Article  Google Scholar 

  65. Bakhtiary, Z., Barar, J., Aghanejad, A., Saei, A. A., Nemati, E., Ezzati Nazhad Dolatabadi, J., & Omidi, Y. (2017). Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer. Drug Development and Industrial Pharmacy, 43(8), 1244–1253.https://doi.org/10.1080/03639045.2017.1310223

  66. Ali, S., Sudha, K. G., Karunakaran, G., Kowsalya, M., Kolesnikov, E., & Rajeshkumar, M. P. (2021). Green synthesis of stable antioxidant, anticancer and photocatalytic activity of zinc oxide nanorods from Leea asiatica leaf. Journal of Biotechnology, 329, 65–79. https://doi.org/10.1016/j.jbiotec.2021.01.022

    Article  Google Scholar 

  67. Surapaneni, S. K., Bhat, Z. R., & Tikoo, K. (2020). MicroRNA-941 regulates the proliferation of breast cancer cells by altering histone H3 Ser 10 phosphorylation. Scientific Reports, 10(1), 17954. https://doi.org/10.1038/s41598-020-74847-7

    Article  Google Scholar 

  68. Bordi, M., De Cegli, R., Testa, B., Nixon, R. A., Ballabio, A., & Cecconi, F. (2021). A gene toolbox for monitoring autophagy transcription. Cell Death & Disease, 12(11), 1044. https://doi.org/10.1038/s41419-021-04121-9

    Article  Google Scholar 

  69. Greeshma, M., Manoj, G. S., & Murugan, K. (2017). Phytochemical analysis of leaves of teak (Tectona grandis LF) BY GC MS. Kongunadu Research Journal, 4(1), 75–78. https://doi.org/10.26524/krj181

    Article  Google Scholar 

  70. Nami, Y., Abdullah, N., Haghshenas, B., Radiah, D., Rosli, R., & Khosroushahi, A. Y. (2014). Assessment of probiotic potential and anticancer activity of newly isolated vaginal bacterium Lactobacillus plantarum 5BL. Microbiology and Immunology, 58(9), 492–502. https://doi.org/10.1111/1348-0421.12175

    Article  Google Scholar 

  71. Zafar, S., Faisal, S., Jan, H., Ullah, R., Rizwan, M., Abdullah, … & Khattak, A. (2022). Development of iron nanoparticles (FeNPs) using biomass of enterobacter: Its characterization, antimicrobial, anti-Alzheimer’s, and enzyme inhibition potential. Micromachines, 13(8), 1259.

  72. Parsian, M., Mutlu, P., Yalcin, S., Tezcaner, A., & Gunduz, U. (2016). Half generations magnetic PAMAM dendrimers as an effective system for targeted gemcitabine delivery. International Journal of Pharmaceutics, 515(1–2), 104–113. https://doi.org/10.1016/j.ijpharm.2016.10.015

    Article  Google Scholar 

  73. Ullah, R., Shah, S., Muhammad, Z., Shah, S. A., Faisal, S., Khattak, U., … & Taj Akbar, M. (2021). In vitro and in vivo applications of Euphorbia wallichii shoot extract-mediated gold nanospheres. Green Processing and Synthesis, 10(1), 101–111.

  74. Arshad, P., Dineshkumar, P., Naga Jyothi, K., Karthik, M., & Saravanan, G. (2019). Dendrimers as a novel carrier in anti-HIV therapy. Journal of Drug Delivery and Therapeutics, 9(5-s), 195–200. https://doi.org/10.22270/jddt.v9i5-s.3650

  75. Rajesh, R., Kumar, S. S., & Venkatesan, R. (2014). Efficient degradation of azo dyes using Ag and Au nanoparticles stabilized on graphene oxide functionalized with PAMAM dendrimers. New Journal of Chemistry, 38(4), 1551. https://doi.org/10.1039/c3nj01050c

    Article  Google Scholar 

  76. Clogston, J. D., & Patri, A. K. (2011). Zeta potential measurement (pp. 63–70). https://doi.org/10.1007/978-1-60327-198-1_6

  77. Jan, H., Shah, M., Andleeb, A., Faisal, S., Khattak, A., Rizwan, M., … & Abbasi, B. H. (2021). Plant‐based synthesis of zinc oxide nanoparticles (ZnO‐NPs) using aqueous leaf extract of Aquilegia pubiflora: Their antiproliferative activity against HepG2 cells inducing reactive oxygen species and other in vitro properties. Oxidative Medicine and Cellular Longevity, 2021(1), 4786227.

  78. Torres-Pérez, S. A., del Ramos-Godínez, M. P., & Ramón-Gallegos, E. (2020). Glycosylated one-step PAMAM dendrimers loaded with methotrexate for target therapy in breast cancer cells MDA-MB-231. Journal of Drug Delivery Science and Technology, 58, 101769.https://doi.org/10.1016/j.jddst.2020.101769

  79. Gunasangkaran, G., Ravi, A. K., Arumugam, V. A., & Muthukrishnan, S. (2022). Preparation, characterization, and anticancer efficacy of chitosan, chitosan encapsulated piperine and probiotics (Lactobacillus plantarum (MTCC-1407), and Lactobacillus rhamnosus (MTCC-1423) nanoparticles. BioNanoScience, 12(2), 527–539. https://doi.org/10.1007/s12668-022-00961-7

    Article  Google Scholar 

  80. Zeynalzadeh, S., Dehghani, E., Hassani, A., Baradar Khoshfetrat, A., & Salami-Kalajahi, M. (2024). Effect of curcumin-loaded poly(amidoamine) dendrimer on cancer cell lines: A comparison between physical loading and chemical conjugation of drug. Polymer Bulletin, 81(2), 1439–1452. https://doi.org/10.1007/s00289-023-04783-9

    Article  Google Scholar 

  81. Khan, M. I., Shah, S., Faisal, S., Gul, S., Khan, S., Abdullah, … & Shah, W. A. (2022). Monotheca buxifolia driven synthesis of zinc oxide nano material its characterization and biomedical applications. Micromachines, 13(5), 668.

  82. Cheng, Y., Qu, H., Ma, M., Xu, Z., Xu, P., Fang, Y., & Xu, T. (2007). Polyamidoamine (PAMAM) dendrimers as biocompatible carriers of quinolone antimicrobials: An in vitro study. European Journal of Medicinal Chemistry, 42(7), 1032–1038. https://doi.org/10.1016/j.ejmech.2006.12.035

    Article  Google Scholar 

  83. Faisal, S., Al-Radadi, N. S., Jan, H., Abdullah, Shah, S. A., Shah, S., … & Uddin, M. N. (2021). Curcuma longa mediated synthesis of copper oxide, nickel oxide and Cu-Ni bimetallic hybrid nanoparticles: Characterization and evaluation for antimicrobial, anti-parasitic and cytotoxic potentials. Coatings, 11(7), 849.

  84. Ellman, G. L., Courtney, K. D., Andres, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7(2), 88–95. https://doi.org/10.1016/0006-2952(61)90145-9

    Article  Google Scholar 

  85. Faisal, S., Ullah, R., Alotaibi, A., Zafar, S., Rizwan, M., & Tariq, M. H. (2023). Biofabrication of silver nanoparticles employing biomolecules of Paraclostridium benzoelyticum strain: Its characterization and their in-vitro antibacterial, anti-aging, anti-cancer and other biomedical applications. Microscopy Research and Technique, 86(7), 846–861.

    Article  Google Scholar 

  86. Reshadmanesh, A., Rahbarizadeh, F., Ahmadvand, D., & Sofla, F. J. I. (2018). Evaluation of cellular and transcriptional targeting of breast cancer stem cells via anti-HER2 nanobody conjugated PAMAM dendrimers. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup3), 105–115.https://doi.org/10.1080/21691401.2018.1489269

  87. Chen, J.-F., Ding, H.-M., Wang, J.-X., & Shao, L. (2004). Preparation and characterization of porous hollow silica nanoparticles for drug delivery application. Biomaterials, 25(4), 723–727. https://doi.org/10.1016/S0142-9612(03)00566-0

    Article  Google Scholar 

  88. Sukumar, D. T., Gunasangkaran, G., Arumugam, V. A., & Muthukrishnan, S. (2022). Effects of biogenic synthesis of chitosan entrapped silver nanoparticle from Aegle marmelos on human cervical cancer cells (HeLa). Journal of Drug Delivery Science and Technology, 70, 103189. https://doi.org/10.1016/j.jddst.2022.103189

    Article  Google Scholar 

  89. Chan, C., Cai, Z., & Reilly, R. M. (2013). Trastuzumab labeled to high specific activity with 111In by conjugation to G4 PAMAM dendrimers derivatized with multiple DTPA chelators exhibits increased cytotoxic potency on HER2-positive breast cancer cells. Pharmaceutical Research, 30(8), 1999–2009. https://doi.org/10.1007/s11095-013-1044-1

    Article  Google Scholar 

  90. Bielawski, K., Bielawska, A., Muszyńska, A., Popławska, B., & Czarnomysy, R. (2011). Cytotoxic activity of G3 PAMAM-NH2 dendrimer-chlorambucil conjugate in human breast cancer cells. Environmental Toxicology and Pharmacology, 32(3), 364–372. https://doi.org/10.1016/j.etap.2011.08.002

    Article  Google Scholar 

  91. Pooja, D., Srinivasa Reddy, T., Kulhari, H., Kadari, A., Adams, D. J., Bansal, V., & Sistla, R. (2020). N-acetyl-d-glucosamine-conjugated PAMAM dendrimers as dual receptor-targeting nanocarriers for anticancer drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 154, 377–386. https://doi.org/10.1016/j.ejpb.2020.07.020

    Article  Google Scholar 

  92. Lewińska, A., Wróbel, K., Błoniarz, D., Adamczyk-Grochala, J., Wołowiec, S., & Wnuk, M. (2022). Lapatinib- and fulvestrant-PAMAM dendrimer conjugates promote apoptosis in chemotherapy-induced senescent breast cancer cells with different receptor status. Biomaterials Advances, 140, 213047. https://doi.org/10.1016/j.bioadv.2022.213047

    Article  Google Scholar 

  93. Mohapatra, P., Preet, R., Das, D., Satapathy, S. R., Choudhuri, T., Wyatt, M. D., & Kundu, C. N. (2012). Quinacrine-mediated autophagy and apoptosis in colon cancer cells is through a p53- and p21-dependent mechanism. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 20(2), 81–91. https://doi.org/10.3727/096504012X13473664562628

    Article  Google Scholar 

  94. Czarnomysy, R., Muszyńska, A., Rok, J., Rzepka, Z., & Bielawski, K. (2021). Mechanism of anticancer action of novel imidazole platinum(II) complex conjugated with G2 PAMAM-OH dendrimer in breast cancer cells. International Journal of Molecular Sciences, 22(11), 5581. https://doi.org/10.3390/ijms22115581

    Article  Google Scholar 

  95. Li, C., Liu, H., Sun, Y., Wang, H., Guo, F., Rao, S., … & Jiang, C. (2009). PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt-TSC2-mTOR signaling pathway. Journal of Molecular Cell Biology, 1(1), 37–45. https://doi.org/10.1093/jmcb/mjp002

Download references

Acknowledgements

All co-authors would like to express our sincere gratitude towards Dr. K. M. Saradhadevi, Assistant Professor, Department of Biochemistry, for her constant moral support and guidance throughout this research work and the Government of Tamil Nadu for providing financial support through the Tamil Nadu State Council for Science and Technology (TNSCST) (Letter No. TNSCST/STP/MS-02/2019-20/3722; Dated: 29.03.2021), Directorate of Technical Education Campus, Chennai, 600025.

Funding

This work was supported by the Tamil Nadu State Council for Science and Technology (TNSCST) (Letter No. TNSCST/STP/MS-02/2019-20/3722; Dated: 29.03.2021), Directorate of Technical Education Campus, Chennai, 600025. Dr. K. M. Saradhadevi has received research support from TNSCST.

Author information

Author notes

  1. Gayathiri Gunasangkaran, Anjali K. Ravi, Sobiya Ramaraju Amirthalakshmi, and Durganjali Gandhi have an equal contribution.

Authors and Affiliations

  1. Department of Biochemistry, Bharathiar University, Coimbatore, Tamilnadu, India

    Saradhadevi Muthukrishnan, Gayathiri Gunasangkaran, Anjali K. Ravi, Sobiya Ramaraju Amirthalakshmi & Durganjali Gandhi

  2. Department of Human Genetics and Molecular Genetics, Bharathiar University, Coimbatore, Tamil Nadu, India

    Vijaya Anand Arumugam

  3. Department of Biotechnology, Bharathiar University, Coimbatore, Tamilnadu, India

    Velayuthaprabhu Shanmugam & Arun Muthukrishnan

  4. Department of Biochemistry, PSG College of Arts and Science, Coimbatore, Tamilnadu, India

    Kunnathur Murugesan Sakthivel

  5. PG & Research, Department of Biochemistry, St. Josephs College of Arts & Science, Cuddalore, Tamilnadu, India

    Marie Arockianathan Pushpam

  6. Department of Agriculture and Animal sciences, Gandhigram Rural Institute Deemed University, Gandhigram, 624 302, Tamilnadu, India

    Ashokkumar kaliyaperumal

  7. Department of Botany, Bharathiar University, Coimbatore, Tamilnadu, India

    Gurusaravanan Packiaraj

Authors
  1. Saradhadevi Muthukrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gayathiri Gunasangkaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anjali K. Ravi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sobiya Ramaraju Amirthalakshmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Durganjali Gandhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vijaya Anand Arumugam
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Velayuthaprabhu Shanmugam
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kunnathur Murugesan Sakthivel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marie Arockianathan Pushpam
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ashokkumar kaliyaperumal
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gurusaravanan Packiaraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Arun Muthukrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Saradhadevi Muthukrishnan: corresponding and first author makes a sustainable contribution to the intellectual input and conceptual designing of the whole paper.

Gayathiri Gunasangkaran, Anjali K. Ravi, Sobiya Ramaraju Amirthalakshmi, and Durganjali Gandhi: drafting the article, formal analysis, methodology, and submitting the final version of the article.

Vijaya Anand Arumugam: makes a sustainable contribution to the intellectual input and design of the whole paper.

Velayuthaprabhu Shanmugam, Kunnathur Murugesan Sakthivel, Marie Arockianathan Pushpam, Ashokkumar Kaliyaperumal, Gurusaravanan Packiaraj, and Arun Muthukrishnan: co-authors who might assist the corresponding author and first author in writing the article and validate the article.

Corresponding author

Correspondence to Saradhadevi Muthukrishnan.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Research Involving Humans and Animals Statement

Not applicable.

Informed Consent

Not applicable. 

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muthukrishnan, S., Gunasangkaran, G., Ravi, A.K. et al. Molecular Mechanism of Novel PAMAM Dendrimer Decorated Tectona grandis and Lactobacillus plantarum Nanoparticles on Autophagy-Induced Apoptosis in TNBC Cells. BioNanoSci. (2024). https://doi.org/10.1007/s12668-024-01532-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12668-024-01532-8

Keywords

Search

Navigation