Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)
Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apopto...
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MDPI AG
2016-06-01
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| author | Ming-Hung Lin Yi-Hui Lee Hsiao-Ling Cheng Huei-Yu Chen Fong-Han Jhuang Pin Ju Chueh |
| author_facet | Ming-Hung Lin Yi-Hui Lee Hsiao-Ling Cheng Huei-Yu Chen Fong-Han Jhuang Pin Ju Chueh |
| author_sort | Ming-Hung Lin |
| collection | DOAJ |
| description | Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression. |
| first_indexed | 2024-12-21T01:57:51Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T01:57:51Z |
| publishDate | 2016-06-01 |
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| series | Molecules |
| spelling | doaj.art-2ad16cb5d3e1473ba5ddc792e711bee02022-12-21T19:19:42ZengMDPI AGMolecules1420-30492016-06-0121784910.3390/molecules21070849molecules21070849Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)Ming-Hung Lin0Yi-Hui Lee1Hsiao-Ling Cheng2Huei-Yu Chen3Fong-Han Jhuang4Pin Ju Chueh5Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanInstitute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, TaiwanBladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.http://www.mdpi.com/1420-3049/21/7/849apoptosiscancercapsaicinsilent mating type information regulation 1 (sirtuin1, SIRT1)tumor-associated NADH oxidase (tNOXENOX2) |
| spellingShingle | Ming-Hung Lin Yi-Hui Lee Hsiao-Ling Cheng Huei-Yu Chen Fong-Han Jhuang Pin Ju Chueh Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1) Molecules apoptosis cancer capsaicin silent mating type information regulation 1 (sirtuin1, SIRT1) tumor-associated NADH oxidase (tNOX ENOX2) |
| title | Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1) |
| title_full | Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1) |
| title_fullStr | Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1) |
| title_full_unstemmed | Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1) |
| title_short | Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1) |
| title_sort | capsaicin inhibits multiple bladder cancer cell phenotypes by inhibiting tumor associated nadh oxidase tnox and sirtuin1 sirt1 |
| topic | apoptosis cancer capsaicin silent mating type information regulation 1 (sirtuin1, SIRT1) tumor-associated NADH oxidase (tNOX ENOX2) |
| url | http://www.mdpi.com/1420-3049/21/7/849 |
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