Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.
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PMID:Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells. 1559 19

Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a major pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloid. It has been shown to induce apoptosis in many cell types. The effects of vanilloids on apoptosis induction are thought to be correlated with the length and degree of the unsaturation of the fatty acyl chains. In this study, we compared the effect of capsaicin and its docosahexaenoic acid (DHA, C22:6) analog (we named as dohevanil) on human breast cancer MCF-7 cells, which do not express caspase-3. Dohevanil, which was synthesized from DHA and vanillylamine, has longer and highly unsaturated fatty acyl chain than capsaicin. We showed that both vanilloids exhibit effects of growth inhibition and DNA fragmentation induction in MCF-7 cells. These effects of dohevanil were more potent than capsaicin. Because these effects were inhibited by z-VAD-fmk, a broad-spectrum caspase inhibitor, the vanilloids induced the apoptosis via caspase-dependent pathway not involving caspase-3. In conclusion, dohevanil has a more potent effect on apoptosis induction in MCF-7 cells than capsaicin.
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PMID:Apoptosis induction by dohevanil, a DHA substitutive analog of capsaicin, in MCF-7 cells. 1626 2

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a significant pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloid. It has been shown to exert biological activities (anticarcinogenic, antimutagenic and chemopreventive) in many cancer cell lines. It was found that capsaicin induces dose-dependent growth inhibition of MCF-7 cells, which does not express caspase-3. In this study, we investigated the molecular mechanism of capsaicin-induced apoptosis in MCF-7 cells. Treatment with capsaicin for 24 h resulted in dose-dependent apoptosis in these cells. After the addition of capsaicin, the levels of reactive oxygen species were reduced slightly in the earlier stage of treatment. Interestingly, an elevation of intracellular calcium ion concentration was detected in the MCF-7 cells. In time course and dosage studies, the mitochondrial membrane potential of MCF-7 cells decreased. However, the change was not significant. It is worth noting that the apoptosis-inducing factor translocated into the cytosol and nucleus from the mitochondria. Our results suggest that capsaicin induces cellular apoptosis through a caspase-independent pathway in MCF-7 cells, and that reactive oxygen species and intracellular calcium ion fluctuation has a minimal role in the process.
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PMID:Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. 1921 24

Chondrosarcoma is a common form of bone cancer which effects the fibrous connective tissue around a joint. It most commonly develops in legs, arms, shoulder blades, rib cage, and pelvis. Capsaicin is an active bitter compound found in red pepper, the fruit of the species Capsicum annuum, and it has been shown to have a lethal effect on different types of cancer. However, to date, investigation of its effect on human chondrosarcoma cells has remained limited. In the study presented here, we determined IC50 values of capsaicin for chondrosarcoma and chondrocyte cells in both fetal bovine serum (FBS)-containing and FBS-deprived media, and no statistically significant difference was found between the cell types. Besides, when the cells were cultured with capsaicin at their determined IC50 value for 24 h and their caspase-3 gene expression levels were detected by real-time polymerase chain reaction (RTPCR) and western blotting, it was demonstrated that the caspase-3 protein and mRNA levels were not altered in any cells upon capsaicin exposure, suggesting a caspase-independent pathway for cell death. Migration and invasion abilities of the cancerous cells, on the other hand, were observed to decrease dramatically when the cells were exposed to capsaicin (P < 0.05).
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PMID:In vitro evaluation of the effects of capsaicin on normal and cancerous cells of human cartilage. 3093 Jun 26

The use of molecules inspired by natural scaffolds has proven to be a very promising and efficient method of drug discovery. In this work, capsaicin, a natural product from Capsicum peppers with antitumor properties, was used as a prototype to obtain urea and thiourea analogues. Among the most promising compounds, the thiourea compound 6g exhibited significant cytotoxic activity against human melanoma A2058 cells that was twice as high as that of capsaicin. Compound 6g induced significant and dose-dependent G0/G1 cell cycle arrest in A2058 cells triggering cell death by apoptosis. Our results suggest that 6g modulates the RAF/MEK/ERK pathway, inducing important morphological changes, such as formation of apoptotic bodies and increased levels of cleaved caspase-3. Compared to capsaicin, 6g had no significant TRPV1/6 agonist effect or irritant effects on mice. Molecular modeling studies corroborate the biological findings and suggest that 6g, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. Inverse virtual screening strategy found MEK1 as a possible biological target for 6g. Consistent with these findings, our observations suggested that 6g could be developed as a potential anticancer agent.
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PMID:Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: Design, synthesis and molecular modeling. 3110 85