Genotoxicity of capsaicin to yeast cells

MDM2-mediated p53 ubiquitilation plays an important role in the regulation of p53 stability. As the data shown above, p53 stability was substantially enhanced after exposure to capsaicin, so we further investigated whether capsaicin regulated p53 stability in a MDM2-mediated manner. Utilizing p53 antibody to immunoprecipitate p53 and then detecting MDM2-p53 interaction with MDM2 antibody, or inversely, with MDM2 antibody to immunoprecipitate p53 and testing the interaction with p53 antibody, we found that capsaicin strongly suppressed the interaction between MDM2 and p53 in a dose-dependent manner, at the concentration of 40 μM, the binding of MDM2 to p53 was substantially decreased and there was nearly no MDM2 binding was detected at 160 μM (shown in Figure A and B). Along with the suppression of MDM2-p53 interaction, MDM2-mediated p53 ubiquitylation was also remarkably reduced after capsaicin treatment, which contributed to the stabilization of p53 and the extension of p53 half-life after capsaicin treatment.

Mechanism of capsaicin in the growth inhbition toyeast cells:

Detoxification of capsaicin by a PDR-type ABCsuperfamily of multi-drug resistance transporters

Of course, over time the capsaicin will dissipate on its own.

shows that administration of TOFA 1 h prior to treatment of HepG2 cells with 0.5 mM capsaicin for 12 h completely blocked the generation of ROS from approximately 260% back to 100% of the control. Deprivation of fatty acid alone following TOFA administration failed to increase ROS production. Thus, we suggest that accumulation of malonyl-CoA following FASN inhibition by capsaicin might be able to cause ROS generation, correlating with mitochondrial impairment and apoptosis induction in HepG2 cells.

T1 - The site of action of capsaicin on the guinea-pig isolated ileum

This study evaluated the selective impact of capsaicin on apoptotic induction mediated by FASN inhibition on HepG2 cells but not on normal human hepatocytes. We used normal human hepatocytes to represent control cells which have low FASN expression and enzymatic activities. The present finding is consistent with previous studies that showed that normal hepatocytes were characterized by a 5-fold lower FASN protein expression (data not shown), lower fatty acid, and triglyceride synthesis than HepG2 cells, as shown in . Previous studies have shown that FASN expression and its activity in normal cells are many times lower than that in cancer cells . Hepatocytes treated with 0.5 mM of capsaicin for 3 h had a comparable level of FASN protein expression and enzymatic activities to the control group. Furthermore, hepatocytes treated with 0.5 mM capsaicin for 6 h did not show any changes of mitochondrial integrity as shown in . These findings clearly suggest that capsaicin inducing FASN inhibition and enzymatic activities leading to induction apoptosis is selective in HepG2 cells but not in normal human hepatocytes. Thus, it affirms that FASN would be a potential target for anti-cancer therapy of capsaicin.

Insects are also affected by capsaicin.

4. Sicuteri F, Fusco BM, Marabini S, Campagnolo V, Maggi CA, Geppetti P. . Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. 1989;5:49-53

The action of CAP on this mechanism is likely TRPV‐1‐independent.

Colon cancer is an increasingly prevalent health problem in China with over 400,000 new cases and 100,000 deaths occurring as a result of the disease every year []. In contrast with the prevalence of this disease, the limited therapeutic options provide a strong stimulus for the development of novel therapeutics. Large numbers of previous experiments have consolidated capsaicin's activity in cancer prevention, and moreover, it was shown that capsaicin -induced apoptosis played an important role in its antitumor activity. However, the underlying mechanism of how capsaicin induce tumor cell to undergo apoptosis were not fully understood. In present study, we have demonstrated that capsaicin had a profound antitumor activity in human colon cancer . Capsaicin treatment has stabilized and activated p53 by dissociating it from MDM2 and capsaicin exerted its activity in a p53 dependent manner.

Decrease of capsaicinoid content following cellular disruption.

Knockdown of p53 in HCT116 severely impaired its sensitivity to capsaicin. A, knockdown p53 expression in HCT116 with specific p53 shRNA. Validation of p53 expression by Western blotting (left panels), the representative photographs (middle panels), and graph (right panel) of the difference of the anchorage-independent growth between mock and p53 knockdown group. B, sensitivity of HCT116 cells to capsaicin after p53 knockdown. Representative photographs of p53 knockdown HCT116 cells after capsaicin treatment (left panels), the graph (right panel) was the result of three independent experiments expressed as means ± SD. HCT116 cells with Mock shRNA or p53 shRNA were treated with 40 μM capsaicin for anchorage independent assay. C, p21 expression and the G0/G1 arrest in p53-knockdown HCT116 cells after capsaicin treatment. HCT116 cells with Mock shRNA or p53 shRNA were treated with indicated concentrations of capsaicin for 24 hrs, the cells were split into two aliquots, one for cell cycle analysis and the other for immunoblot. D, apoptotic-related protein expression (Bax, cleaved-PARP, caspase 3) and capsaicin-induced apoptosis in p53-knockdown HCT116 cell after capsaicin treatment. HCT116 cells with Mock shRNA or p53 shRNA were treated with 160 μM capsaicin for indicated time points, then the cells were split into two aliquots, one was subjected to Annexin V-PI double staining and the other was subjected to immunoblot. The asterisks (Student's test) indicated a significant difference.