In situ hybridization on human colon tissue demonstrates that epidermal growth factor receptor (E... more In situ hybridization on human colon tissue demonstrates that epidermal growth factor receptor (EGFR) mRNA expression is strongly increased during tumour progression. To obtain test systems to evaluate the relevance of growth factor action during carcinogenesis, primary cultures from human colorectal carcinomas were established. EGFR distribution was determined in 2 of the 27 primary cultures and was compared with that
1,25 Dihydroxyvitamin D3 (1,25-D3) can be considered an antitumorigenic agent, which can be used ... more 1,25 Dihydroxyvitamin D3 (1,25-D3) can be considered an antitumorigenic agent, which can be used in the therapy of malignant diseases such as prostate cancer. In this respect, it is important to note that some prostatic cancer cells express high levels of CYP24, a cytochrome enzyme involved in degradation of 1,25-D3. Genistein, a widely occurring isoflavonoid, inhibits cytochrome enzymes and also exerts antitumorigenic effects. Here, we therefore investigated the effect of genistein on cytochrome enzymes involved in vitamin D metabolism. Treatment of DU-145 prostatic cancer cells with genistein led to a time- and dose-dependent inhibition of CYP24. Additionally CYP27B1 was also inhibited. CYP27B1 is the cytochrome enzyme that synthesizes 1,25-D3. RT-PCR showed that the effect of genistein was mainly due to inhibition of transcription. This often involves the activity of histone deacetylases (HDAC). Thus we tested if the HDAC inhibitor trichostatin A (TSA) reversed the effect of genistein on vitamin D hydroxylases. TSA per se reduced expression of CYP24 mRNA and synergized with genistein to abolish expression after an incubation of 24 h. Importantly, TSA, which itself did not affect CYP27B1 expression, rescued CYP27B1 from transcriptional inhibition by genistein. In conclusion, our data argue for the use of genistein to resensitize prostate cancer cells to 1,25-D3; the addition of TSA may preserve the ability of these cells to synthesize 1,25-D3.
There is growing evidence that vitamin D exerts anticarcinogenic effects. Ultraviolet-B (UV-B) ra... more There is growing evidence that vitamin D exerts anticarcinogenic effects. Ultraviolet-B (UV-B) radiation, which is required for vitamin D production in the skin, was found to be inversely associated with cancer incidence and mortality. Recent studies have largely but not consistently shown that low 25-hydroxyvitamin D (25(OH)D) levels, which are considered to be the best indicator of vitamin D status, are a significant risk factor for cancer mortality. Circulating 25(OH)D levels were also associated with improved survival in colorectal and lung cancer patients and vitamin D insufficiency was observed in various other diseases such as autoimmune, infectious, musculoskeletal, neurological and cardiovascular diseases. In conclusion, we still need further studies to evaluate the association of vitamin D insufficiency and cancer incidence and mortality, but the multiple health benefits of vitamin D and the easy, safe and inexpensive way by which vitamin D can be supplemented should already guide current public health strategies to achieve 25(OH)D levels of at least 75 nmol/l (30 ng/ml) in the general population.
Although embryonic chick small intestinal segments provide a very limited amount of tissue for pr... more Although embryonic chick small intestinal segments provide a very limited amount of tissue for preparation of enterocyte brush border membrane vesicles (BBMV), we were able to develop a procedure for isolation of BBMV from cultured 20-d-old embryonic chick jejunum in high yield by modifying a divalent cation precipitation method. Total yield of the brush border marker enzyme alkaline phosphatase in the vesicle fraction as compared to the crude homogenate was approximately 40%, and the specific activity of the enzyme was increased 25-fold on the average. The brush border membrane vesicle fraction was only contaminated with other cellular organelles (basolateral membranes, mitochondria, lysosomes or endoplasmic reticulum) to a minor extent. Functional integrity of the brush border vesicles was indicated by Na+ gradient-driven electrogenic D-glucose transport leading to concentrative transfer (overshoot) of the sugar into an osmotically active intravesicular space. When jejuna were cul...
In situ hybridization on human colon tissue demonstrates that epidermal growth factor receptor (E... more In situ hybridization on human colon tissue demonstrates that epidermal growth factor receptor (EGFR) mRNA expression is strongly increased during tumour progression. To obtain test systems to evaluate the relevance of growth factor action during carcinogenesis, primary cultures from human colorectal carcinomas were established. EGFR distribution was determined in 2 of the 27 primary cultures and was compared with that
1,25 Dihydroxyvitamin D3 (1,25-D3) can be considered an antitumorigenic agent, which can be used ... more 1,25 Dihydroxyvitamin D3 (1,25-D3) can be considered an antitumorigenic agent, which can be used in the therapy of malignant diseases such as prostate cancer. In this respect, it is important to note that some prostatic cancer cells express high levels of CYP24, a cytochrome enzyme involved in degradation of 1,25-D3. Genistein, a widely occurring isoflavonoid, inhibits cytochrome enzymes and also exerts antitumorigenic effects. Here, we therefore investigated the effect of genistein on cytochrome enzymes involved in vitamin D metabolism. Treatment of DU-145 prostatic cancer cells with genistein led to a time- and dose-dependent inhibition of CYP24. Additionally CYP27B1 was also inhibited. CYP27B1 is the cytochrome enzyme that synthesizes 1,25-D3. RT-PCR showed that the effect of genistein was mainly due to inhibition of transcription. This often involves the activity of histone deacetylases (HDAC). Thus we tested if the HDAC inhibitor trichostatin A (TSA) reversed the effect of genistein on vitamin D hydroxylases. TSA per se reduced expression of CYP24 mRNA and synergized with genistein to abolish expression after an incubation of 24 h. Importantly, TSA, which itself did not affect CYP27B1 expression, rescued CYP27B1 from transcriptional inhibition by genistein. In conclusion, our data argue for the use of genistein to resensitize prostate cancer cells to 1,25-D3; the addition of TSA may preserve the ability of these cells to synthesize 1,25-D3.
There is growing evidence that vitamin D exerts anticarcinogenic effects. Ultraviolet-B (UV-B) ra... more There is growing evidence that vitamin D exerts anticarcinogenic effects. Ultraviolet-B (UV-B) radiation, which is required for vitamin D production in the skin, was found to be inversely associated with cancer incidence and mortality. Recent studies have largely but not consistently shown that low 25-hydroxyvitamin D (25(OH)D) levels, which are considered to be the best indicator of vitamin D status, are a significant risk factor for cancer mortality. Circulating 25(OH)D levels were also associated with improved survival in colorectal and lung cancer patients and vitamin D insufficiency was observed in various other diseases such as autoimmune, infectious, musculoskeletal, neurological and cardiovascular diseases. In conclusion, we still need further studies to evaluate the association of vitamin D insufficiency and cancer incidence and mortality, but the multiple health benefits of vitamin D and the easy, safe and inexpensive way by which vitamin D can be supplemented should already guide current public health strategies to achieve 25(OH)D levels of at least 75 nmol/l (30 ng/ml) in the general population.
Although embryonic chick small intestinal segments provide a very limited amount of tissue for pr... more Although embryonic chick small intestinal segments provide a very limited amount of tissue for preparation of enterocyte brush border membrane vesicles (BBMV), we were able to develop a procedure for isolation of BBMV from cultured 20-d-old embryonic chick jejunum in high yield by modifying a divalent cation precipitation method. Total yield of the brush border marker enzyme alkaline phosphatase in the vesicle fraction as compared to the crude homogenate was approximately 40%, and the specific activity of the enzyme was increased 25-fold on the average. The brush border membrane vesicle fraction was only contaminated with other cellular organelles (basolateral membranes, mitochondria, lysosomes or endoplasmic reticulum) to a minor extent. Functional integrity of the brush border vesicles was indicated by Na+ gradient-driven electrogenic D-glucose transport leading to concentrative transfer (overshoot) of the sugar into an osmotically active intravesicular space. When jejuna were cul...
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