1. Academic Validation
  2. Jervine exhibits anticancer effects on nasopharyngeal carcinoma through promoting autophagic apoptosis via the blockage of Hedgehog signaling

Jervine exhibits anticancer effects on nasopharyngeal carcinoma through promoting autophagic apoptosis via the blockage of Hedgehog signaling

  • Biomed Pharmacother. 2020 Dec;132:110898. doi: 10.1016/j.biopha.2020.110898.
Jing Chen 1 Bin Wen 2 Yu Wang 1 Sheng Wu 1 Xuesong Zhang 3 Yonggui Gu 4 Zhiyi Wang 5 Jianjiang Wang 6 Wenzhong Zhang 5 Ji Yong 7
Affiliations

Affiliations

  • 1 Department of Pathology, Jingjiang People's Hospital, Jingjiang, Jiangsu, 214500, China.
  • 2 Department of Oncology, Jingjiang Chinese Medicine Hospital, Jingjiang, Jiangsu, 214500, China.
  • 3 Central Laboratory, Jingjiang People's Hospital, Jingjiang, Jiangsu, 214500, China.
  • 4 Department of Otolaryngology, Jingjiang People's Hospital, Jingjiang, Jiangsu, 214500, China.
  • 5 Department of Otolaryngology, East Theater General Hospital of PLA, Nanjing, Jiangsu, 210000, China.
  • 6 Department of General Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu, 214500, China.
  • 7 Department of Otolaryngology, East Theater General Hospital of PLA, Nanjing, Jiangsu, 210000, China. Electronic address: yongjijjph@foxmail.com.
Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the superior mucosal epithelium of the nasopharynx. However, effective therapies for NPC are still required. Reducing Hedgehog signaling pathway has been shown to suppress tumor growth. In this study, we attempted to explore whether Jervine (JV), an inhibitor of Hedgehog signaling, had anti-cancer effects on NPC, and the underlying mechanisms. Our findings showed that JV treatments markedly reduced the proliferation of NPC cells in a dose- and time-dependent manner. Cell cycle arrest in G2/M phase was significantly enhanced by JV, along with evident DNA damage. Moreover, JV treatment effectively induced Apoptosis in NPC cells through improving Caspase-3 activation. Furthermore, ROS production and mitochondrial impairments were detected in JV-incubated NPC cells with elevated releases of Cyto-c from mitochondria. JV also dramatically triggered Autophagy through blocking Akt/mTOR and increasing AMPK signaling pathways. Intriguingly, we showed that JV-induced Apoptosis was mainly via an autophagy-dependent manner. In addition, the expression levels of SHH, PTCH1, Smo and GLI1 were markedly suppressed in NPC cells, demonstrating the hindered Hedgehog signaling. Importantly, we found that JV-induced Apoptosis and Autophagy were closely associated with the blockage of Hedgehog signaling. Our in vivo studies confirmed the anti-cancer effects of JV on NPC through inducing Autophagy, as evidenced by the markedly reduced tumor growth rate and weight without side effects and toxicity. Taken together, JV may be a promising and effective agent for human NPC treatment through repressing Hedgehog signaling pathway and inducing autophagic cell death.

Keywords

Apoptosis; Autophagy; Hedgehog signaling; Jervine; Nasopharyngeal carcinoma.

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