2. Academic Validation
  3. Discovery of a novel ferroptosis inducer-talaroconvolutin A-killing colorectal cancer cells in vitro and in vivo

Discovery of a novel ferroptosis inducer-talaroconvolutin A-killing colorectal cancer cells in vitro and in vivo

  • Cell Death Dis. 2020 Nov 17;11(11):988. doi: 10.1038/s41419-020-03194-2.
Yong Xia 1 2,  Shuzhi Liu 3,  Changlin Li 4,  Zhiying Ai 4,  Wenzhi Shen 4,  Wenqi Ren 4,  Xiaolong Yang 5
Affiliations

Affiliations

  • 1 Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, 272067, Jining, Shandong, P.R. China. xiayong@mail.jnmc.edu.cn.
  • 2 Departments of Urology, New York University School of Medicine, New York, NY, 10016, USA. xiayong@mail.jnmc.edu.cn.
  • 3 The Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central University for Nationalities, 430074, Wuhan, P.R. China.
  • 4 Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, 272067, Jining, Shandong, P.R. China.
  • 5 The Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central University for Nationalities, 430074, Wuhan, P.R. China. yxl19830915@163.com.
PMID: 33203867 DOI: 10.1038/s41419-020-03194-2
Abstract

Ferropotsis is among the most important mechanisms of Cancer suppression, which could be harnessed for Cancer therapy. However, no natural small-molecule compounds with Cancer inhibitory activity have been identified to date. In the present study, we reported the discovery of a novel Ferroptosis inducer, talaroconvolutin A (TalaA), and the underlying molecular mechanism. We discovered that TalaA killed colorectal Cancer cells in dose-dependent and time-dependent manners. Interestingly, TalaA did not induce Apoptosis, but strongly triggered Ferroptosis. Notably, TalaA was significantly more effective than erastin (a well-known Ferroptosis inducer) in suppressing colorectal Cancer cells via Ferroptosis. We revealed a dual mechanism of TalaA' action against Cancer. On the one hand, TalaA considerably increased Reactive Oxygen Species levels to a certain threshold, the exceeding of which induced Ferroptosis. On the other hand, this compound downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate Lipoxygenase 3 (ALOXE3), promoting Ferroptosis. Furthermore, in vivo experiments in mice evidenced that TalaA effectively suppressed the growth of xenografted colorectal Cancer cells without obvious liver and kidney toxicities. The findings of this study indicated that TalaA could be a new potential powerful drug candidate for colorectal Cancer therapy due to its outstanding ability to kill colorectal Cancer cells via Ferroptosis induction.

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