| Status | 已發表Published |
| MAM, a natural naphthoquinone, induces necroptosis in colon cancer cells | |
Chen, X. P. ; Sun, W. ; Gao, H.W.; Lu, J.
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| 2017-08-01 | |
| Source Publication | ICMAN‐IUPHAR Natural Products
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| Abstract | Necroptosis is a recently identified programmed cell death. Here, we reported that MAM, a natural naphthoquinone isolated from Huzhang, caused hydrogen peroxide dependent activation of JNK and induced the expression of iNOS, thereby leading to nitric oxide generation in A549 lung cancer cells. In addition, a decrease in GSH/GSSG levels accompanied with increased ROS production was observed. Reversal of ROS generation and cell death in GSH pretreated cells indicated the involvement of GSH depletion in MAM mediated cytotoxicity. Furthermore, MAM treated HCT116 and HT29 cells, accompanied by mitochondrial ROS elevation, mitochondrial depolarization and ATP depletion. This process was identified as necroptosis, based on the experiments showing that MAM-induced cell death was attenuated by RIP1 inhibitor necrostatin-1s, siRNA-mediated gene silencing of RIP1 and RIP3. RIP1/RIP3 complex triggered necroptosis by accumulation of cytosolic calcium, followed by sustained JNK activation. Finally, we determined that both calcium chelator BAPTA-AM and JNK inhibitor SP600125 could mitochondrial ROS elevation, mitochondrial depolarization and ATP depletion. In addition, MAM induced necroptosis was independent of TNFα, p53, MLKL, and LMP. MAM dramatically inhibited the growth of lung cancer on A549 human lung cancer xenografts of nude mice. In summary, MAM induced necroptosis in cancer cells and showed anti-cancer effect in animal model. |
| Keyword | MAM Cancer |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 39146 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Chen, X. P. |
| Recommended Citation GB/T 7714 | Chen, X. P.,Sun, W.,Gao, H.W.,et al. MAM, a natural naphthoquinone, induces necroptosis in colon cancer cells[C], 2017. |
| APA | Chen, X. P.., Sun, W.., Gao, H.W.., & Lu, J. (2017). MAM, a natural naphthoquinone, induces necroptosis in colon cancer cells. ICMAN‐IUPHAR Natural Products. |
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