Resibufogenin suppresses colorectal cancer growth and metastasis through RIP3-mediated necroptosis

Journal of Translational Medicine
Qinrui HanXuegang Sun

Abstract

Necroptotic susceptibility is probably an intrinsic weakness of cancer. Here, we report that resibufogenin, a member of bufadienolide family, suppresses the growth and metastasis of colorectal cancer (CRC) through induction of necroptosis in vivo. SW480 cells with stably expressing enhanced green fluorescence protein were xenografted to BALB/c-nu mice to observe the growth of tumors. Liver metastasis was observed by injection of MC38 cells beneath the splenic capsule of mice. Protein expression was determined by immunohistochemistry, immunofluorescence and western blot. Consolidated in vitro results indicate that resibufogenin has anti-proliferative activity on CRC cells. PI staining and transmission electron microscope imaging suggest that the cell death induced by resibufogenin are mainly through necrosis, which is further confirmed by the ineffectiveness of z-VAD, a pan-caspase general inhibitor. In particular, resibufogenin induced necrosis is substantially abrogated in receptor-interacting protein kinase 3 (RIPK3) knockout mouse embryo fibroblasts. The RIP3-dependent necrosis has been classified as necroptosis. Resibufogenin triggeres necroptosis through upregulating RIP3 and phosphorylating mixed lineage kinase domain-lik...Continue Reading

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Citations

Jul 12, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Qian LiPing Mo
Jan 22, 2020·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Lian-Dong ShenGuang-Cai Cao
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Aug 13, 2021·Cell Death Discovery·Yan LiuZuozhang Yang

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Methods Mentioned

BETA
surgical resection
xenografts
flow cytometry
Assay
PCR
fluorescence imaging

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