Modulatory effects of Thai medicinal plant extract on proinflammatory cytokines-induced apoptosis in human keratinocyte HaCaT cells

It has been experimentally proven that proinflammatory cytokines, interferon (IFN)-y and tumor necrosis factor (TNF)-a are able to synergistically induce apoptosis in HaCaT keratinocyte cells. The present study aimed to elucidate modulatory effects of ethanolic extracts derived from Thai traditional medicinal plants on IFN-y/TNF-a-caused HaCaT apoptosis and correlate with their natural phenolic content. Using 3-(4-5 dimethylthiozol-2-yl) 2-5 diphenyl-tetrazolium bromide (MTT) assay, we found that herbal extracts derived from members of the Acanthaceae family, Rhinacanthus nasutus (L.) Kurz (0.1, 1 and 10 μg/ml) and Clinacanthus nutans (Burm.f.) Lindau (1 and 100 μg/ml), significantly inhibited the IFN-y/TNF-a- induced HaCaT apoptosis, while members of the Zingiberaceae family, Curcuma longa L. and Alpinia galanga (L.) Willd, significantly enhanced apoptosis when a concentration of 100 μg/ml was used. Furthermore, the ethanolic plant extracts were found to possess different amounts of total phenolics ranging from 1.64 to 10.04 mg GAE/g as determined using Folin-Ciocalteu assay. The richest phenolic sources were R. nasutus (10.04 ± 1.12 mg GAE/g) and C. longa (7.49 ± 0.50 mg GAE/g), whereas the least phenolic source was Centella asiatica (1.64 ± 0.84 mg GAE/g). Taken together, we found certain modulatory effects of Thai medicinal extracts on IFN-y/TNF-a-induced apoptosis in HaCaT cells, but these findings might not be directly correlated with their natural phenolic  content. Therefore, further investigations on different types of natural phenolic contents in these Thai medicinal extracts and their relevant molecular mechanisms in keratinocytes, should be carried out in the near future.Key words: Interferon, tumor necrosis factor, Thai medicinal herbs, apoptosis, phenolics, human keratinocytes

PTEN deficiency and mutant p53 confer glucose-addiction to thyroid cancer cells: impact of glucose depletion on cell proliferation, cell survival, autophagy and cell migration.

Proliferating cancer cells oxidize glucose through the glycolytic pathway. Since this metabolism is less profitable in terms of ATP production, cancer cells consume large quantity of glucose, and those that experience insufficient blood supply become glucose-addicted. We have analyzed the response to glucose depletion in WRO and FTC133 follicular thyroid cancer cells, which differ in the expression of two key regulators of the glucose metabolism. WRO cells, which express wild type p53 and PTEN, showed a higher rate of cell proliferation and were much less sensitive to glucose-depletion than FTC133 cells, which are PTEN null and express mutant p53. Glucose depletion slowed-down the autophagy flux in FTC133 cells, not in WRO cells. In a wound-healing assay, WRO cells were shown to migrate faster than FTC133 cells. Glucose depletion slowed down the cell migration rate, and these effects were more evident in FTC133 cells. Genetic silencing of either wild-type PTEN or p53 in WRO cells resulted in increased uptake of glucose, whereas the ectopic expression of PTEN in FTC133 cells resulted in diminished glucose uptake. In conclusion, compared to WRO, FTC133 cells were higher glucose up-taker and consumer. These data do not support the general contention that cancer cells lacking PTEN or expressing the mutant p53R273H are more aggressive and prone to better face glucose depletion. We propose that concurrent PTEN deficiency and mutant p53 leads to a glucose-addiction state that renders the cancer cell more sensitive to glucose restriction. The present observation substantiates the view that glucose-restriction may be an adjuvant strategy to combat these tumours

Protection from UVB Toxicity in Human Keratinocytes by Thailand Native Herbs Extracts.

Thai traditional medicine employs a wide range of indigenous herbs in the forms of tincture or tea for the cure of skin and systemic inflammatory diseases. The protection by Thai plants extracts against UVB DNA damage and cytotoxicity was investigated in human keratinocytes. Petroleum ether, dichloromethane and ethanol extracts were prepared from 15 Thai herb species, and the total phenolic and flavonoid contents, the antioxidant and UV-absorbing properties were assessed by standard procedures. Cytoprotective effects were evaluated on the basis of cell survival, caspase-3 activity and pyrimidine dimers determination. High total phenolic and flavonoid contents were found in the ethanol and dichloromethane fractions. Dichloromethane extract of turmeric was shown to possess the highest antioxidant activity. The maximum UV absorptions were found in the ethanol extract of turmeric and in the dichloromethane extract of ginger. These extracts stimulated the synthesis of Thioredoxin 1, an antioxidant protein, and could protect human HaCaT keratinocytes from UV-induced DNA damage and cytotoxicity. The present data support the utilization of turmeric and ginger extracts in anti-UV cosmetic pharmaceuticals

PTEN deficiency and mutant p53 confer glucose-addiction to thyroid cancer cells: impact of glucose depletion on cell proliferation, cell survival, autophagy and cell migration

Proliferating cancer cells oxidize glucose through the glycolytic pathway. Since this metabolism is less profitable in terms of ATP production, cancer cells consume large quantity of glucose, and those that experience insufficient blood supply become glucose-addicted. We have analyzed the response to glucose depletion in WRO and FTC133 follicular thyroid cancer cells, which differ in the expression of two key regulators of the glucose metabolism. WRO cells, which express wild type p53 and PTEN, showed a higher rate of cell proliferation and were much less sensitive to glucose-depletion than FTC133 cells, which are PTEN null and express mutant p53. Glucose depletion slowed-down the autophagy flux in FTC133 cells, not in WRO cells. In a wound-healing assay, WRO cells were shown to migrate faster than FTC133 cells. Glucose depletion slowed down the cell migration rate, and these effects were more evident in FTC133 cells. Genetic silencing of either wild-type PTEN or p53 in WRO cells resulted in increased uptake of glucose, whereas the ectopic expression of PTEN in FTC133 cells resulted in diminished glucose uptake. In conclusion, compared to WRO, FTC133 cells were higher glucose up-taker and consumer. These data do not support the general contention that cancer cells lacking PTEN or expressing the mutant p53R273H are more aggressive and prone to better face glucose depletion. We propose that concurrent PTEN deficiency and mutant p53 leads to a glucoseaddiction state that renders the cancer cell more sensitive to glucose restriction. The present observation substantiates the view that glucose-restriction may be an adjuvant strategy to combat these tumours