Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

Lin, H Y; Hsieh, Ming‐Ju; Hsi, Yi‐Ting; Lo, Yu‐Sheng; Chuang, Yi‐Ching; Chen, Mu‐Kuan; Chien, Su‐Yu

doi:10.3892/ol.2017.6346

Cited by 22 publications

(13 citation statements)

References 21 publications

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“…Expression of cleaved PARP (p85) was also increased compared with control cells, altogether indicating that induction of the caspase apoptotic pathway may be one mechanism for brevilin-A-induced cell apoptosis. This is consistent with previous articles, which showed that cleaved caspase 9 and cleaved PARP were found in apoptotic cells after treatment with brevilin A (Lin et al, 2017; Wang et al, 2018).…”

Section: Discussionsupporting

confidence: 93%

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Zhao

Lin

et al. 2019

Front. Pharmacol.

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Nasopharyngeal carcinoma (NPC) is one of the most common malignant cancers in Southeast Asia and Southern China. Centipeda minima extract (CME) had previously demonstrated anti-cancer effects in human NPC. Brevilin A, a sesquiterpene lactone isolated from C. minima , has been reported to exhibit biological activities. In this study, we investigated its anti-NPC effect and further explored its molecular mechanisms. The effects of brevilin A were tested in the NPC cell lines CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. Effects of brevilin A on cell viability were determined by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. The molecular mechanism of cell cycle regulation and apoptosis were investigated via Western blot. Results showed that brevilin A inhibited NPC cell viability in a concentration- and time-dependent manner. Brevilin A induced cell cycle arrest at G2/M and induced apoptosis. Western blot results demonstrated that brevilin A could down-regulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, while up-regulating cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by brevilin A showed dynamic changes according to dose and time. In the tumor xenograft model, brevilin A could reduce tumor growth, at a similar magnitude to cisplatin. However, notably, whereas cisplatin treatment led to significant weight loss in treated mice, treatment with brevilin A did not, indicating its relative lack of toxicity. Taken together, brevilin A regulated cell cycle, activated the caspase signaling pathway, and inhibited PI3K/AKT/mTOR and STAT3 signaling pathways in vitro , and exhibited similar efficacy to the common chemotherapeutic cisplatin in vivo , without its associated toxicity. These findings provide a framework for the preclinical development of brevilin A as a chemotherapeutic for NPC.

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Section: Discussionsupporting

confidence: 93%

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Zhao

Lin

et al. 2019

Front. Pharmacol.

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“…Expression of cleaved PARP (p85) was also increased, altogether suggesting the caspase apoptotic pathway as a mechanism for arnicolide-D-induced cell apoptosis. This is consistent with previous studies that showed increased cleaved caspase 9 and cleaved PARP in apoptotic cells [27,39].…”

Section: Discussionsupporting

confidence: 94%

Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma

Chan

Mok

et al. 2019

Molecules

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Nasopharyngeal carcinoma (NPC) is a high morbidity and mortality cancer with an obvious racial and geographic bias, particularly endemic to Southeast China. Our previous studies demonstrated that Centipeda minima extract (CME) exhibited anti-cancer effects in human NPC cell lines. Arnicolide C and arnicolide D are sesquiterpene lactones isolated from Centipeda minima. In this study, for the first time, we investigated their anti-NPC effects and further explored the related molecular mechanisms. The effects of both arnicolide C and arnicolide D were tested in NPC cells CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. The results showed that the two compounds inhibited NPC cell viability in a concentration- and time-dependent manner. As the inhibitory effect of arnicolide D was the more pronounced of the two, our following studies focused on this compound. Arnicolide D could induce cell cycle arrest at G2/M, and induce cell apoptosis. The molecular mechanism of cell cycle regulation and apoptosis induction was investigated, and the results showed that arnicolide D could downregulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, and upregulate cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by arnicolide D showed dynamic changes according to dose and time. Taken together, arnicolide D modulated the cell cycle, activated the caspase signaling pathway, and inhibited the PI3K/AKT/mTOR and STAT3 signaling pathways. These findings provide a solid base of evidence for arnicolide D as a lead compound for further development, and act as proof for the viability of drug development from traditional Chinese medicines.

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“…TCM has been developed for cancer research and many Chinese herbal medicines have been demonstrated to inhibit cancer. Celastrol is a triterpene from TCM, which demonstrates anti-proliferative activity in HONE-1 and NPC-039 cell lines and induces apoptosis through the death receptor and mitochondrial pathway in human NPC cells, which makes it a promising candidate in the development of drugs for treating NPC ( 24 ). Evodiamine inhibits the migration and invasive ability of NPC cells and metastasis targeting matrix metalloproteinase-2 ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Curcumol attenuates epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via TGF-β1

et al. 2018

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The current study aimed to identify the effect and primary mechanism of Curcumol on the migration of nasopharyngeal carcinoma (NPC) cells in vitro and in vivo. Curcumol was dissolved in absolute ethyl alcohol and the experiment was performed in NPC 5–8F cells in vitro and in vivo. The effect of different concentrations of Curcumol on cell migration was determined using wound healing and Transwell assays. A cell counting kit-8 (CCK-8) assay was also performed in order to determine cell viability. Flow cytometry was used to detect the effect of Curcumol on apoptosis. The expression of epithelial-mesenchymal transition (EMT)-associated proteins and genes was evaluated by western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA. In addition, the antitumor activity of Curcumol was investigated in female BALB/C nude mice with orthotopic tumor implants. The results indicated that cell apoptosis was increased and the viability of NPC 5–8F cells was decreased following treatment with Curcumol at doses of 0.1, 0.2 and 0.4 µM/ml. The results of in vivo experiments indicated that tumor growth and weight were decreased following Curcumol administration. Furthermore, the results of western blotting and RT-qPCR demonstrated that Curcumol altered the level of E-cadherin and N-cadherin in a dose-dependent manner in vivo. Curcumol also regulated the secretion of protein markers in the serum that were associated with EMT and TGF-β1 in the 5–8F xenograft mouse model. Thus, the results indicated that Curcumol induced TGF-β1-mediated EMT arrest by regulating E-cadherin and N-cadherin, which may prevent further development of NPC.

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Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

Cited by 22 publications

References 21 publications

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma

Curcumol attenuates epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via TGF-β1

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