Resveratrol induces apoptosis of human nasopharyngeal carcinoma cells via activation of multiple apoptotic pathways

Huang, Tsung Teng; Lin, Hung Chi; Chen, Chang Chieh; Lu, Chia Chen; Wei, Chia Fong; Liu, Fu Guo; Lai, Hsin‐Chih

doi:10.1002/jcp.22391

Cited by 30 publications

(28 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It seems that MCL-induced mitochondrial damage seems to be the cause rather than the effect of MCL-induced cell death because the phenomenon was detectable as early as 3 hours after treatment (data not shown). These results agree with the prevailing response of most cancer cells exposed to chemotherapeutic components (7,16,39).…”

Section: Discussionsupporting

confidence: 90%

“…Apoptosis is executed by caspases and caspase-3 is a key protease associated with DNA fragmentation and apoptosis (39). Two main pathways have been involved in activation of caspase-3, including the caspase-8-regulated plasma membrane extrinsic pathway and the caspase-9-regulated cell damage intrinsic pathway (39).…”

Section: Discussionmentioning

confidence: 99%

“…Two main pathways have been involved in activation of caspase-3, including the caspase-8-regulated plasma membrane extrinsic pathway and the caspase-9-regulated cell damage intrinsic pathway (39). We determined that MCL exposure caused direct activation of both caspase-8 and caspase-9, followed by activation of caspase-3 and cleavage of PARP (one of the early DNA damage responses; Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Bcl2 phosphorylation has been shown to inhibit cell-cycle progression by delaying the G 1 -S transition (27,53). Furthermore, the proapoptotic proteins Bak and Bid can inhibit cell-cycle progression, inhibit cell survival, and increase apoptosis (7,27,39). Strikingly, MCL had no significant effects on the production of these proteins.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Fang

Zhang

et al. 2012

Cancer Prevention Research

View full text Add to dashboard Cite

The incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions, including southern China, northern Africa, and North America. One of the promising therapeutic approaches on NPC is drug screening from natural products, such as components from traditional Chinese medicine. In this study, the antitumor activity of Momordica charantia lectin (MCL), a type II ribosome inactivating protein from bitter gourd, on NPC was investigated. MCL evinced potent cytotoxicity toward NPC CNE-1 (IC 50 ¼ 6.9) and CNE-2 (IC 50 ¼ 7.4) cells but minimally affected normal NP 69 cells. Further investigation disclosed that MCL induced apoptosis, DNA fragmentation, G 1 -phase arrest, and mitochondrial injury in both types of NPC cells. The reduction of cyclin D1 and phosphoretinoblastoma (Rb) protein expression contributed to arrest at G 1 -phase of the cell cycle. These events were associated with regulation of mitogen-activated protein kinases (MAPK; including p38 MAPK, JNK, and ERK) phosphorylation and promoted downstream nitric oxide (NO) production. Concurrent administration of the p38 MAPK inhibitor SB-203580 significantly diminished NO production and lethality of MCL toward NPC cells. Further studies revealed that MCL increased cytochrome c release into the cytosol, activated caspases-8, -9, and -3, and enhanced production of cleaved PARP, subsequently leading to DNA fragmentation and apoptosis. Finally, an intraperitoneal injection of MCL (1.0 mg/kg/d) led to an average of 45% remission of NPC xenograft tumors subcutaneously inoculated in nude mice. This is the first article that unveils the potential of a type II RIP, MCL, for prevention and therapy of NPC.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Fang

Zhang

et al. 2012

Cancer Prevention Research

View full text Add to dashboard Cite

show abstract

“…To date, only three in vitro studies have suggested the potential inhibitory effects of resveratrol on human NPC cells (33)(34)(35). The underlying molecular mechanisms remain largely unknown, and there is also a lack of in vivo evidence to support the anticancer activity in human NPC.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol inhibits human nasopharyngeal carcinoma cell growth via blocking pAkt/p70S6K signaling pathways

Zhang¹,

Zhou²,

Zhou³

2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. 4' , has been shown to exert potent anticancer effects on various types of cancer through its anti-proliferative, anti-angiogenic, antioxidant and pro-apoptotic functions. There is still a lack of experimental evidence regarding whether resveratrol has potential anticancer activity in human nasopharyngeal carcinoma (NPC) cells. The purpose of this study was to explore the anticancer activity of resveratrol in human NPC cells both in vitro and in vivo. Our results indicated that treatment with resveratrol led to a time-and dose-dependent decrease in cell proliferation in NPC cells. A dose-dependent increase in apoptosis in response to resveratrol treatment was also observed in NPC cells. Flow cytometric analysis showed that treatment of NPC cells with resveratrol led to cell cycle arrest at the S and G2/M phases. Mechanistically, resveratrol treatment downregulated the expression of Bcl-2 and hypoxia-inducible factor-1α (HIF-1α) proteins and upregulated the expression of caspase-3 protein. In addition, resveratrol treatment also significantly decreased the phosphorylation levels of Akt1, p70S6K and p-4E-BP-1 and the protein expression of several cyclins involved in cell cycle regulation. In vivo studies further showed that resveratrol was able to significantly inhibit the growth of NPC tumor xenografts in nude mice. Collectively, our findings suggest that resveratrol exerts potent anti-proliferative and pro-apoptotic effects on human NPC cells possibly through interfering with the pAkt1/p70S6K signaling pathways, thus it may potentially be developed as an effective agent for chemoprevention and chemotherapy of human NPC.

show abstract

Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway

et al. 2015

View full text Add to dashboard Cite

Resveratrol (RSV), a natural polyphenols, has been suggested to induce cell cycle arrest and activate apoptosis-mediated cell death in several cancer cells, including prostate cancer. However, several molecular mechanisms have been proposed on its chemopreventive action, the precise mechanisms by which RSV exerts its anti-proliferative effect in androgen-independent prostate cancer cells remain questionable. In the present study, we show that RSV activates autophagic cell death in PC3 and DU145 cells, which was dependent on stromal interaction molecule 1 (STIM1) expression. RSV treatment decreases STIM1 expression in a time dependent manner and attenuates STIM1 association with TRPC1 and Orai1. Furthermore, RSV treatment also decreases ER calcium storage and store operated calcium entry (SOCE), which induces endoplasmic reticulum (ER) stress thereby activating AMPK and inhibiting the AKT/mTOR pathway. Similarly, inhibition of SOCE by SKF-96365 decreases the survival and proliferation of PC3 and DU145 cells and inhibits AKT/mTOR pathway and induces autophagic cell death. Importantly, SOCE inhibition and subsequent autophagic cell death caused by RSV was reversed by STIM1 overexpression. STIM1 overexpression restored SOCE, prevent the loss of mTOR phosphorylation and decreased the expression of CHOP and LC3A in PC3 cells. Taken together, for the first time, our results revealed that RSV induces autophagy mediated cell death in PC3 and DU145 cells through regulation of SOCE mechanisms, including down regulating STIM1 expression and trigger ER stress by depleting ER calcium pool.

show abstract

Resveratrol induces apoptosis of human nasopharyngeal carcinoma cells via activation of multiple apoptotic pathways

Cited by 30 publications

References 51 publications

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

Resveratrol inhibits human nasopharyngeal carcinoma cell growth via blocking pAkt/p70S6K signaling pathways

Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway

Contact Info

Product

Resources

About