1. Academic Validation
  2. BIX-01294, a G9a inhibitor, suppresses cell proliferation by inhibiting autophagic flux in nasopharyngeal carcinoma cells

BIX-01294, a G9a inhibitor, suppresses cell proliferation by inhibiting autophagic flux in nasopharyngeal carcinoma cells

  • Invest New Drugs. 2021 Jun;39(3):686-696. doi: 10.1007/s10637-020-01053-7.
Qian Li 1 Liuqian Wang 1 Di Ji 1 Xiaomin Bao 1 Guojing Tan 1 Xiaojun Liang 1 Ping Deng 2 Huifeng Pi 2 Yonghui Lu 2 Chunhai Chen 2 Mindi He 2 Lei Zhang 2 Zhou Zhou 3 Zhengping Yu 2 Anchun Deng 4
Affiliations

Affiliations

  • 1 Department of Otolaryngology Head and Neck Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  • 2 Department of Occupational Health, Army Medical University (Third Military Medical University), Chongqing, China.
  • 3 Department of Environmental Medicine, Department of Emergency Medicine of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Department of Otolaryngology Head and Neck Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China. 260019300@qq.com.
Abstract

G9a, a Histone Methyltransferase, has been found to be upregulated in a range of tumor tissues, and contributes to tumor growth and metastasis. However, the impact of G9a inhibition as a potential therapeutic target in nasopharyngeal carcinoma (NPC) is unclear. In the present study we aimed to investigate the anti-proliferative effect of G9a inhibition in the NPC cell lines CNE1 and CNE2, and to further elucidate the molecular mechanisms underlying these effects. The expression of G9a in NPC tumor tissues was significantly higher than that in normal nasopharyngeal tissues. The pharmacological inhibition of G9a by BIX-01294 (BIX) inhibited proliferation and induced caspase-independent Apoptosis in NPC cells in vitro. Treatment with BIX induced autophagosome accumulation, which exacerbated the cytotoxic activity of BIX in NPC cells. Mechanistic studies have found that BIX impairs autophagosomes by initiating Autophagy in a Beclin-1-independent way, and impairs autophagic degradation by inhibiting lysosomal Cathepsin D activation, leading to lysosomal dysfunction. BIX was able to suppress tumor growth, possibly by inhibiting autophagic flux; it might therefore constitute a promising candidate for NPC therapy.

Keywords

Autophagy; BIX-01294; G9a; Inhibitor; Nasopharyngeal carcinoma.

Figures
Products
Inhibitors & Agonists
Other Products