1. Academic Validation
  2. Fangchinoline Inhibits Human Esophageal Cancer by Transactivating ATF4 to Trigger Both Noxa-Dependent Intrinsic and DR5-Dependent Extrinsic Apoptosis

Fangchinoline Inhibits Human Esophageal Cancer by Transactivating ATF4 to Trigger Both Noxa-Dependent Intrinsic and DR5-Dependent Extrinsic Apoptosis

  • Front Oncol. 2021 Jun 14;11:666549. doi: 10.3389/fonc.2021.666549.
Yunjing Zhang 1 Shiwen Wang 1 2 Yukun Chen 1 Junqian Zhang 1 Jing Yang 1 Jingrong Xian 1 2 Lihui Li 1 Hu Zhao 2 Robert M Hoffman 3 4 Yanmei Zhang 2 Lijun Jia 1
Affiliations

Affiliations

  • 1 Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 2 Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
  • 3 Department of Surgery, University of California, San Diego, San Diego, CA, United States.
  • 4 Anticancer Inc., San Diego, CA, United States.
Abstract

Esophageal squamous cell carcinoma (ESCC) is a recalcitrant Cancer. The Chinese herbal monomer fangchinoline (FCL) has been reported to have anti-tumor activity in several human Cancer cell types. However, the therapeutic efficacy and underlying mechanism on ESCC remain to be elucidated. In the present study, for the first time, we demonstrated that FCL significantly suppressed the growth of ESCC both in vitro and in vivo. Mechanistic studies revealed that FCL-induced G1 phase cell-cycle arrest in ESCC which is dependent on p21 and p27. Moreover, we found that FCL coordinatively triggered Noxa-dependent intrinsic Apoptosis and DR5-dependent extrinsic Apoptosis by transactivating ATF4, which is a novel mechanism. Our findings elucidated the tumor-suppressive efficacy and mechanisms of FCL and demonstrated FCL is a potential anti-ESCC agent.

Keywords

cell cycle; esophageal squamous cell carcinoma (ESCC); extrinsic apoptosis; fangchinoline (FCL); intrinsic apoptosis.

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