2. Academic Validation
  3. A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis

A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis

  • Cancer Lett. 2016 Oct 10;381(1):14-22. doi: 10.1016/j.canlet.2016.07.008.
Ning Li 1,  Lin Feng 1,  Hui-Qiong Han 1,  Jing Yuan 1,  Xue-Kang Qi 1,  Yi-Fan Lian 1,  Bo-Hua Kuang 1,  Yu-Chen Zhang 1,  Cheng-Cheng Deng 1,  Hao-Jiong Zhang 1,  You-Yuan Yao 1,  Miao Xu 1,  Gui-Ping He 1,  Bing-Chun Zhao 1,  Ling Gao 1,  Qi-Sheng Feng 1,  Li-Zhen Chen 1,  Lu Yang 1,  Dajun Yang 2,  Yi-Xin Zeng 3
Affiliations

Affiliations

  • 1 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
  • 2 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Ascentage Pharma Group Corp. Limited, Taizhou 225309, China. Electronic address: yangdj@sysucc.org.cn.
  • 3 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Beijing Hospital, Beijing 100730, China. Electronic address: zengyx@sysucc.org.cn.
PMID: 27424523 DOI: 10.1016/j.canlet.2016.07.008
Abstract

Despite advances in the development of radiation against nasopharyngeal carcinoma (NPC), the management of advanced NPC remains a challenge. Smac mimetics are designed to neutralize inhibitor of Apoptosis (IAP) proteins, thus reactivating the apoptotic program in Cancer cells. In this study, we investigated the effect of a novel bivalent Smac mimetic APG-1387 in NPC. In vitro, APG-1387 in combination with TNF-α potently decreased NPC cell viability by inducing Apoptosis in majority of NPC cell lines. The in vitro antitumor effect was RIPK1-dependent, whereas it was independent on IAPs, USP11, or EBV. Of note, the inhibition of NF-κB or Akt pathway rendered resistant NPC cells responsive to the treatment of APG-1387/TNF-α. In vivo, APG-1387 displayed antitumor activity as a single agent at well-tolerated doses, even in an in vitro resistant cell line. In summary, our results demonstrate that APG-1387 exerts a potent antitumor effect on NPC. These findings support clinical evaluation of APG-1387 as a potential treatment for advanced NPC.

Keywords

AKT; Apoptosis; NF-κB; Nasopharyngeal carcinoma; Smac mimetic.

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