2. Academic Validation
  3. Shuganning injection, a traditional Chinese patent medicine, induces ferroptosis and suppresses tumor growth in triple-negative breast cancer cells

Shuganning injection, a traditional Chinese patent medicine, induces ferroptosis and suppresses tumor growth in triple-negative breast cancer cells

  • Phytomedicine. 2021 May:85:153551. doi: 10.1016/j.phymed.2021.153551.
Jingjing Du 1,  Lishuang Wang 1,  Xiaoming Huang 1,  Na Zhang 1,  Ze Long 1,  You Yang 1,  Fangfang Zhong 1,  Bowen Zheng 1,  Wenjian Lan 2,  Wanjun Lin 1,  Wenzhe Ma 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
  • 2 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
  • 3 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. Electronic address: [email protected].
PMID: 33827043 DOI: 10.1016/j.phymed.2021.153551
Abstract

Background: Triple-negative breast Cancer (TNBC), lacking targeted therapies currently, is susceptible to Ferroptosis, a recently defined form of cell death.

Purpose: To evaluate the Anticancer activity of Shuganning injection (SGNI), a traditional Chinese patent medicine, on TNBC cells; To elucidate the mechanism of SGNI induced Ferroptosis.

Methods: The Anticancer activity of SGNI was examined via in vitro cell proliferation assays and in vivo xenograft growth assay. Ferroptosis was determined by flow-cytometric analysis of lipid ROS, labile iron pool measurement, and propidium iodide exclusion assay. The dependency on heme oxygenase 1 (HO-1) of SGNI induced Ferroptosis was confirmed by genetic knockdown and pharmacological inhibition of the protein.

Results: SGNI selectively inhibited the proliferation of TNBC cells compared to non-TNBC breast Cancer cells and normal cells. The cell death induced by SGNI in TNBC cells showed distinct morphology from Apoptosis and could not be rescued by the pan-caspase inhibitor Z-VAD(OMe)-FMK. On the Other hand, SGNI induced cell death was blocked by the lipid ROS scavengers ferrostatin-1 and liproxstatin-1, the acyl-CoA synthetase long chain family member 4 inhibitor rosiglitazone, and the iron chelators 1,10-phenanthroline and deferoxamine. These data indicated that SGNI induced a ferroptotic cell death of TNBC cells. Mechanistically, SGNI induced Ferroptosis was dependent on HO-1, which promotes intracellular labile iron pool accumulation, and was alleviated by HO-1 knockdown and inhibition by tin protoporphyrin IX. In line with the in vitro data, SGNI significantly inhibited the xenograft growth of TNBC cell line MD-MB-231 in nude mice.

Conclusion: Collectively, our study elaborates on a promising regimen for TNBC treatment through induction of Ferroptosis by SGNI, a traditional Chinese patent medicine currently available in the clinic, which merits further investigation.

Keywords

Ferroptosis; Shuganning injection; Triple-negative breast cancer.

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