The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is us... more The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is usually associated with poor prognosis and drug resistance. Therapies targeting the epidermal growth factor receptor (EFGR) are widely used for end-stage CRC. However, patients with KRAS mutant genes cannot benefit from this therapy because of Ras signaling activation by KRAS mutant genes. Our previous study revealed the anti-proliferative effect of 4-acetyl-antroquinonol B (4-AAQB) on CRC cells, but whether the drug is effective in KRAS-mutant CRC remains unknown. We screened CRC cell lines harboring the KRAS mutation, namely G12A, G12C, G12V and G13D, with one wild type cell line as the control; SW1463 and Caco-2 cell lines were used for further experiments. Sulforhodamine B assays, together with the clonogenicity and invasion assay, revealed that KRAS-mutant SW1463 cells were resistant to cetuximab; however, 4-AAQB treatment effectively resensitized CRC cells to cetuximab through the re...
Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the worl... more Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated β-catenin, phosphatidylinositol-3 kinase (PI...
Phytomedicine : international journal of phytotherapy and phytopharmacology, Jan 15, 2018
The cancer stem cells (CSCs) have been shown to play key roles in the oral cancer initiation, dis... more The cancer stem cells (CSCs) have been shown to play key roles in the oral cancer initiation, distant metastasis, the development of chemoresistance and recurrence after treatment. Therefore, the inhibition of oral CSCs has been the target for therapeutic development. In this study, we investigated the anti-CSCs potential of Ovatodiolide (Ova), a diterpenoid isolate of Anisomeles indica, in vitro and in vivo. Oral CSCs were treated with Ova, and the expression of pluripotency factors Oct4, Sox-2, and Nanog were evaluated by western blot. Effect of Ova on self-renewal capacity and clonogenicity were assessed with the sphere formation and clonogenic assay in CSCs model derived from oral cancer cell. The effect of Ova was also investigated in a mouse xenograft model obtained by injecting nude mice with oral CSCs cells. We demonstrated that Ova significantly and dose-dependently suppressed oral cancer cell viability and colony formation; Ova markedly inhibited the ALDH1 activities and r...
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcom... more Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P=0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreas...
Novel analytical methods (UHPLC/DAD/qTOF-MS, SFC/MS, IC/PAD) were established to determine chiral... more Novel analytical methods (UHPLC/DAD/qTOF-MS, SFC/MS, IC/PAD) were established to determine chiral ergostanes, lanostanes and polysaccharide compositions in Antrodia cinnamomea.
The study of the anticancer effects of destruxin B (DB) is rare and its anticancer mechanism rema... more The study of the anticancer effects of destruxin B (DB) is rare and its anticancer mechanism remains unknown. The aim of this study was to test the in vitro and in vivo anticancer effects of DB, on human HT-29 colorectal cancer (CRC). DB was isolated and characterized by high pressure liquid chromatography, electrospray ionization mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the effects of DB on HT-29 cells in vitro. The anticancer effects of DB were investigated in a murine xenograft model of human colon cancer. A significant inhibition of cell viability was observed with DB treatment in time- and dose-dependent manners. DB administered subcutaneously daily at 0.6-15 mg/kg was proven to be safe and effective in inhibiting the growth of CRC cells. Expression of Bax, cleaved poly (ADP-ribose) polymerase and active caspase-3 were observed with DB treatment and the increa...
Eleven derivatives from Antrodia camphorata were isolated in order to evaluate their selective cy... more Eleven derivatives from Antrodia camphorata were isolated in order to evaluate their selective cytotoxicity toward 14 types of human cancer cell and two non-transformed cell types. Among these triterpenoids, methyl antcinate A (MAA) exhibited the most potent spectrum of anticancer effects in KB cells, four different oral cancer cell lines (TSCCa, GNM, OC-2, and OEC-M1), Panc-1, BT474, PC-3, OVCAR-3, HeLa, and U2OS cells with high selectivity indices (CC(50)/IC(50)). The expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and poly(ADP-ribose) polymerase (PARP) of PC-3 cells tested by western blotting suggested that MAA exerts cell death through the caspase-dependent cascade and the Bax-mediated mitochondrial apoptotic pathway, not only on liver and oral cancer cells but on other types as well, including prostate cancer, in a dose-dependent manner. In addition to MAA, methyl antcinate B, dehydroeburicoic acid, and 15α-acetyl-dehydrosulfurenic acid also exhibited...
In continuation to our studies toward the identification of direct anti-cancer targets, here we s... more In continuation to our studies toward the identification of direct anti-cancer targets, here we showed that destruxin B (DB) from Metarhizium anisopliae suppressed the proliferation and induced cell cycle arrest in human colorectal cancer (CRC) HT29, SW480 and HCT116 cells. Additionally, DB induced apoptosis in HT29 cells by decreased expression level of anti-apoptotic proteins Bcl-2 and Bcl-xL while increased pro-apoptotic Bax. On the other hand, DB attenuated Wnt-signaling by downregulation of β-catenin, Tcf4 and β-catenin/Tcf4 transcriptional activity, concomitantly with decreased expression of β-catenin target genes cyclin D1, c-myc and survivin. Furthermore, DB affected the migratory and invasive ability of HT29 cells through suppressed MMPs-2 and -9 enzymatic activities. We also found that DB targeted the MAPK and/or PI3K/Akt pathway by reduced expression of Akt, IKK-α, JNK, NF-κB, c-Jun and c-Fos while increased that of IκBα. Finally, we demonstrated that DB inhibited tumorigenesis in HT29 xenograft mice using non-invasive bioluminescence technique. Consistently, tumor samples from DB-treated mice demonstrated suppressed expression of β-catenin, cyclin D1, survivin, and endothelial marker CD31 while increased caspase-3 expression. Collectively, our data supports DB as an inhibitor of Wnt/β-catenin/Tcf signaling pathway that may be beneficial in the CRC management.
Evidence-Based Complementary and Alternative Medicine, 2013
The bacterial pathogenHelicobacter pylori(Hp) is the leading risk factor for the development of g... more The bacterial pathogenHelicobacter pylori(Hp) is the leading risk factor for the development of gastric cancer. Hp virulence factor, cytotoxin-associated gene A (CagA) interacted with cholesterol-enriched microdomains and leads to induction of inflammation in gastric epithelial cells (AGS). In this study, we identified a triterpenoid methylantcinate B (MAB) from the medicinal mushroomAntrodia camphoratawhich inhibited the translocation and phosphorylation of CagA and caused a reduction in hummingbird phenotype in HP-infected AGS cells. Additionally, MAB suppressed the Hp-induced inflammatory response by attenuation of NF-κB activation, translocation of p65 NF-κB, and phosphorylation of IκB-α, indicating that MAB modulates CagA-mediated signaling pathway. Additionally, MAB also suppressed the IL-8 luciferase activity and its secretion in HP-infected AGS cells. On the other hand, molecular structure simulations revealed that MAB interacts with CagA similarly to that of cholesterol. Mo...
A continuous online technique based on electric cell-substrate impedance sensing (ECIS) was used ... more A continuous online technique based on electric cell-substrate impedance sensing (ECIS) was used for probing inhibitory effects on Spodoptera frugiperda Sf9 insect cells exposed to structurally similar compounds isolated and purified from the fruiting bodies of the fungus Antrodia camphorata. Such chemicals consisted of three ergostane-related steroids and five lanosta-related triterpenes, which are known for their diverse properties and use in the formulation of nutraceuticals and functional foods. The half-inhibition concentration (ECIS(50)), the level at which 50% inhibition of the resistance response was obtained, was determined from the response function to establish inhibitory effects of the different isolates. A slight change in their chemical structures resulted in significant effects on inhibition as probed by impedance spectroscopy. The ergostane-related steroids were mostly inhibitory, but replacing their ketone groups with hydrogen or hydroxyl groups significantly reduced the inhibition. Similarly, the addition of methyl or carboxymethyl groups also lowered the inhibition. Removal of the double bond conjugation within the rings (sulfurenic acid) of the isolate drastically reduced the inhibition.
Background/Aim: The current study aimed to identify an attractive target against human oral squam... more Background/Aim: The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC). Materials and Methods: The effect of 3,3’,4’,5’-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively. Results: Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2associated × protein, while reducing the mitochondrial membrane potenti...
International Journal of Applied Science and Engineering, 2009
Traditional Chinese medicinal plant Cinnamomum osmophloeum Kaneh (Lauraceae) has been used as spi... more Traditional Chinese medicinal plant Cinnamomum osmophloeum Kaneh (Lauraceae) has been used as spices and condiments. A simple and accurate reversed-phase high-performance liquid chromatographic (RP-HPLC) separation method was developed for the determination of two bioactive flavonol glycosides, namely kaempferol-3,7-O-α-L-dirhamnoside (kaempferitrin, 1), and kaempferol 3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-7-O-α-L-rhamnopyranoside (2), in leaves of C. osmophloeum. Separation of the two compounds was achieved with a Hypersil BDS C18 column by gradient elution using acetonitrile-water (30:70, v/v) containing 0.1% trifluroacetic acid as a mobile phase. The flow rate and detection wavelength was set at 0.8 ml/min and 265 nm, respectively. Calibration curves were found to be linear within the range of 5-100 μg/mL. The contents of two flavonoids in C. osmophloeum leaves were successfully determined with retention times of 14.8 and 15.5 min. The recovery of the two flavonoids wa...
The current study aimed to identify an attractive target against human oral squamous cell carcino... more The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC). The effect of 3,3',4',5'-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively. Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2-associated × protein, while reducing the mitochondrial membrane potential, and expression of B-cell lympho...
Background: Drug resistance represents a major challenge for treating patients with colon cancer.... more Background: Drug resistance represents a major challenge for treating patients with colon cancer. Accumulating evidence suggests that Insulin-like growth factor (IGF)-associated signaling promotes colon tumorigenesis and cancer stemness. Therefore, the identification of agents, which can disrupt cancer stemness signaling, may provide improved therapeutic efficacy. Methods: Mimicking the tumor microenvironment, we treated colon cancer cells with exogenous IGF1. The increased stemness of IGF1-cultured cells was determined by ALDH1 activity, side-population, tumor sphere formation assays. Destruxin B (DB) was evaluated for its anti-tumorigenic and stemness properties using cellular viability, colony-formation tests. The mimic and inhibitor of miR-214 were used to treat colon cancer cells to show its functional association to DB treatment. In vivo mouse models were used to evaluate DB’s ability to suppress colon tumor-initiating ability and growth inhibitory function. Results: IGF1-cult...
Ovatodiolide was isolated from the traditional Chinese medicinal herb Anisomeles indica, possesse... more Ovatodiolide was isolated from the traditional Chinese medicinal herb Anisomeles indica, possesses anti-bacterial and anti-inflammatory properties; however, the anti-cancer activity and its mechanisms have been limitedly reported. This study aimed to examine the effect and molecular action of ovatodiolide in lung cancer cells. Cell cycle distribution and reactive oxygen species (ROS) generation were measured by flow cytometry. Apoptosis was detected by propidium iodide/annexin V staining and TUNEL assay. DNA damage was investigated by comet assay and γ-H2AX staining. Caspase activity was determined using caspase fluorometric kits. Moreover, protein levels were examined by western blot. Ovatodiolide provoked reactive oxygen species generation and DNA damage, as well as inhibited cell growth and induced apoptosis in human lung cancer A549 and H1299 cell lines. DNA damage-related molecules, ATM/ATR and CHK1/CHK2 were activated by ovatodiolide. Moreover, ovatodiolide-mediated G2/M arres...
Evidence-based complementary and alternative medicine : eCAM, 2017
Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, in Taiwa... more Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC value (for 48 h) was 170 M. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 M); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP-7 expression. Luciferase reporter assay showed that antcin-H repressed the MMP-7 promoter activity, in parallel to inhibiting c-Fos/AP-1 and C/EBP- transactivation abilities. Moreover, antcin-H suppressed the activity of ERK1/2 and decreased the binding ability of C/EBP- and c-Fos on the upstream/enhancer region of MMP-7 promoter. Overall, this study demonstrated that the anti-invasive effect of antcin-H in human rena...
The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is us... more The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is usually associated with poor prognosis and drug resistance. Therapies targeting the epidermal growth factor receptor (EFGR) are widely used for end-stage CRC. However, patients with KRAS mutant genes cannot benefit from this therapy because of Ras signaling activation by KRAS mutant genes. Our previous study revealed the anti-proliferative effect of 4-acetyl-antroquinonol B (4-AAQB) on CRC cells, but whether the drug is effective in KRAS-mutant CRC remains unknown. We screened CRC cell lines harboring the KRAS mutation, namely G12A, G12C, G12V and G13D, with one wild type cell line as the control; SW1463 and Caco-2 cell lines were used for further experiments. Sulforhodamine B assays, together with the clonogenicity and invasion assay, revealed that KRAS-mutant SW1463 cells were resistant to cetuximab; however, 4-AAQB treatment effectively resensitized CRC cells to cetuximab through the re...
Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the worl... more Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated β-catenin, phosphatidylinositol-3 kinase (PI...
Phytomedicine : international journal of phytotherapy and phytopharmacology, Jan 15, 2018
The cancer stem cells (CSCs) have been shown to play key roles in the oral cancer initiation, dis... more The cancer stem cells (CSCs) have been shown to play key roles in the oral cancer initiation, distant metastasis, the development of chemoresistance and recurrence after treatment. Therefore, the inhibition of oral CSCs has been the target for therapeutic development. In this study, we investigated the anti-CSCs potential of Ovatodiolide (Ova), a diterpenoid isolate of Anisomeles indica, in vitro and in vivo. Oral CSCs were treated with Ova, and the expression of pluripotency factors Oct4, Sox-2, and Nanog were evaluated by western blot. Effect of Ova on self-renewal capacity and clonogenicity were assessed with the sphere formation and clonogenic assay in CSCs model derived from oral cancer cell. The effect of Ova was also investigated in a mouse xenograft model obtained by injecting nude mice with oral CSCs cells. We demonstrated that Ova significantly and dose-dependently suppressed oral cancer cell viability and colony formation; Ova markedly inhibited the ALDH1 activities and r...
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcom... more Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P=0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreas...
Novel analytical methods (UHPLC/DAD/qTOF-MS, SFC/MS, IC/PAD) were established to determine chiral... more Novel analytical methods (UHPLC/DAD/qTOF-MS, SFC/MS, IC/PAD) were established to determine chiral ergostanes, lanostanes and polysaccharide compositions in Antrodia cinnamomea.
The study of the anticancer effects of destruxin B (DB) is rare and its anticancer mechanism rema... more The study of the anticancer effects of destruxin B (DB) is rare and its anticancer mechanism remains unknown. The aim of this study was to test the in vitro and in vivo anticancer effects of DB, on human HT-29 colorectal cancer (CRC). DB was isolated and characterized by high pressure liquid chromatography, electrospray ionization mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the effects of DB on HT-29 cells in vitro. The anticancer effects of DB were investigated in a murine xenograft model of human colon cancer. A significant inhibition of cell viability was observed with DB treatment in time- and dose-dependent manners. DB administered subcutaneously daily at 0.6-15 mg/kg was proven to be safe and effective in inhibiting the growth of CRC cells. Expression of Bax, cleaved poly (ADP-ribose) polymerase and active caspase-3 were observed with DB treatment and the increa...
Eleven derivatives from Antrodia camphorata were isolated in order to evaluate their selective cy... more Eleven derivatives from Antrodia camphorata were isolated in order to evaluate their selective cytotoxicity toward 14 types of human cancer cell and two non-transformed cell types. Among these triterpenoids, methyl antcinate A (MAA) exhibited the most potent spectrum of anticancer effects in KB cells, four different oral cancer cell lines (TSCCa, GNM, OC-2, and OEC-M1), Panc-1, BT474, PC-3, OVCAR-3, HeLa, and U2OS cells with high selectivity indices (CC(50)/IC(50)). The expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and poly(ADP-ribose) polymerase (PARP) of PC-3 cells tested by western blotting suggested that MAA exerts cell death through the caspase-dependent cascade and the Bax-mediated mitochondrial apoptotic pathway, not only on liver and oral cancer cells but on other types as well, including prostate cancer, in a dose-dependent manner. In addition to MAA, methyl antcinate B, dehydroeburicoic acid, and 15α-acetyl-dehydrosulfurenic acid also exhibited...
In continuation to our studies toward the identification of direct anti-cancer targets, here we s... more In continuation to our studies toward the identification of direct anti-cancer targets, here we showed that destruxin B (DB) from Metarhizium anisopliae suppressed the proliferation and induced cell cycle arrest in human colorectal cancer (CRC) HT29, SW480 and HCT116 cells. Additionally, DB induced apoptosis in HT29 cells by decreased expression level of anti-apoptotic proteins Bcl-2 and Bcl-xL while increased pro-apoptotic Bax. On the other hand, DB attenuated Wnt-signaling by downregulation of β-catenin, Tcf4 and β-catenin/Tcf4 transcriptional activity, concomitantly with decreased expression of β-catenin target genes cyclin D1, c-myc and survivin. Furthermore, DB affected the migratory and invasive ability of HT29 cells through suppressed MMPs-2 and -9 enzymatic activities. We also found that DB targeted the MAPK and/or PI3K/Akt pathway by reduced expression of Akt, IKK-α, JNK, NF-κB, c-Jun and c-Fos while increased that of IκBα. Finally, we demonstrated that DB inhibited tumorigenesis in HT29 xenograft mice using non-invasive bioluminescence technique. Consistently, tumor samples from DB-treated mice demonstrated suppressed expression of β-catenin, cyclin D1, survivin, and endothelial marker CD31 while increased caspase-3 expression. Collectively, our data supports DB as an inhibitor of Wnt/β-catenin/Tcf signaling pathway that may be beneficial in the CRC management.
Evidence-Based Complementary and Alternative Medicine, 2013
The bacterial pathogenHelicobacter pylori(Hp) is the leading risk factor for the development of g... more The bacterial pathogenHelicobacter pylori(Hp) is the leading risk factor for the development of gastric cancer. Hp virulence factor, cytotoxin-associated gene A (CagA) interacted with cholesterol-enriched microdomains and leads to induction of inflammation in gastric epithelial cells (AGS). In this study, we identified a triterpenoid methylantcinate B (MAB) from the medicinal mushroomAntrodia camphoratawhich inhibited the translocation and phosphorylation of CagA and caused a reduction in hummingbird phenotype in HP-infected AGS cells. Additionally, MAB suppressed the Hp-induced inflammatory response by attenuation of NF-κB activation, translocation of p65 NF-κB, and phosphorylation of IκB-α, indicating that MAB modulates CagA-mediated signaling pathway. Additionally, MAB also suppressed the IL-8 luciferase activity and its secretion in HP-infected AGS cells. On the other hand, molecular structure simulations revealed that MAB interacts with CagA similarly to that of cholesterol. Mo...
A continuous online technique based on electric cell-substrate impedance sensing (ECIS) was used ... more A continuous online technique based on electric cell-substrate impedance sensing (ECIS) was used for probing inhibitory effects on Spodoptera frugiperda Sf9 insect cells exposed to structurally similar compounds isolated and purified from the fruiting bodies of the fungus Antrodia camphorata. Such chemicals consisted of three ergostane-related steroids and five lanosta-related triterpenes, which are known for their diverse properties and use in the formulation of nutraceuticals and functional foods. The half-inhibition concentration (ECIS(50)), the level at which 50% inhibition of the resistance response was obtained, was determined from the response function to establish inhibitory effects of the different isolates. A slight change in their chemical structures resulted in significant effects on inhibition as probed by impedance spectroscopy. The ergostane-related steroids were mostly inhibitory, but replacing their ketone groups with hydrogen or hydroxyl groups significantly reduced the inhibition. Similarly, the addition of methyl or carboxymethyl groups also lowered the inhibition. Removal of the double bond conjugation within the rings (sulfurenic acid) of the isolate drastically reduced the inhibition.
Background/Aim: The current study aimed to identify an attractive target against human oral squam... more Background/Aim: The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC). Materials and Methods: The effect of 3,3’,4’,5’-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively. Results: Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2associated × protein, while reducing the mitochondrial membrane potenti...
International Journal of Applied Science and Engineering, 2009
Traditional Chinese medicinal plant Cinnamomum osmophloeum Kaneh (Lauraceae) has been used as spi... more Traditional Chinese medicinal plant Cinnamomum osmophloeum Kaneh (Lauraceae) has been used as spices and condiments. A simple and accurate reversed-phase high-performance liquid chromatographic (RP-HPLC) separation method was developed for the determination of two bioactive flavonol glycosides, namely kaempferol-3,7-O-α-L-dirhamnoside (kaempferitrin, 1), and kaempferol 3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-7-O-α-L-rhamnopyranoside (2), in leaves of C. osmophloeum. Separation of the two compounds was achieved with a Hypersil BDS C18 column by gradient elution using acetonitrile-water (30:70, v/v) containing 0.1% trifluroacetic acid as a mobile phase. The flow rate and detection wavelength was set at 0.8 ml/min and 265 nm, respectively. Calibration curves were found to be linear within the range of 5-100 μg/mL. The contents of two flavonoids in C. osmophloeum leaves were successfully determined with retention times of 14.8 and 15.5 min. The recovery of the two flavonoids wa...
The current study aimed to identify an attractive target against human oral squamous cell carcino... more The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC). The effect of 3,3',4',5'-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively. Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2-associated × protein, while reducing the mitochondrial membrane potential, and expression of B-cell lympho...
Background: Drug resistance represents a major challenge for treating patients with colon cancer.... more Background: Drug resistance represents a major challenge for treating patients with colon cancer. Accumulating evidence suggests that Insulin-like growth factor (IGF)-associated signaling promotes colon tumorigenesis and cancer stemness. Therefore, the identification of agents, which can disrupt cancer stemness signaling, may provide improved therapeutic efficacy. Methods: Mimicking the tumor microenvironment, we treated colon cancer cells with exogenous IGF1. The increased stemness of IGF1-cultured cells was determined by ALDH1 activity, side-population, tumor sphere formation assays. Destruxin B (DB) was evaluated for its anti-tumorigenic and stemness properties using cellular viability, colony-formation tests. The mimic and inhibitor of miR-214 were used to treat colon cancer cells to show its functional association to DB treatment. In vivo mouse models were used to evaluate DB’s ability to suppress colon tumor-initiating ability and growth inhibitory function. Results: IGF1-cult...
Ovatodiolide was isolated from the traditional Chinese medicinal herb Anisomeles indica, possesse... more Ovatodiolide was isolated from the traditional Chinese medicinal herb Anisomeles indica, possesses anti-bacterial and anti-inflammatory properties; however, the anti-cancer activity and its mechanisms have been limitedly reported. This study aimed to examine the effect and molecular action of ovatodiolide in lung cancer cells. Cell cycle distribution and reactive oxygen species (ROS) generation were measured by flow cytometry. Apoptosis was detected by propidium iodide/annexin V staining and TUNEL assay. DNA damage was investigated by comet assay and γ-H2AX staining. Caspase activity was determined using caspase fluorometric kits. Moreover, protein levels were examined by western blot. Ovatodiolide provoked reactive oxygen species generation and DNA damage, as well as inhibited cell growth and induced apoptosis in human lung cancer A549 and H1299 cell lines. DNA damage-related molecules, ATM/ATR and CHK1/CHK2 were activated by ovatodiolide. Moreover, ovatodiolide-mediated G2/M arres...
Evidence-based complementary and alternative medicine : eCAM, 2017
Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, in Taiwa... more Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC value (for 48 h) was 170 M. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 M); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP-7 expression. Luciferase reporter assay showed that antcin-H repressed the MMP-7 promoter activity, in parallel to inhibiting c-Fos/AP-1 and C/EBP- transactivation abilities. Moreover, antcin-H suppressed the activity of ERK1/2 and decreased the binding ability of C/EBP- and c-Fos on the upstream/enhancer region of MMP-7 promoter. Overall, this study demonstrated that the anti-invasive effect of antcin-H in human rena...
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