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  2. Schisandrin B induces HepG2 cells pyroptosis by activating NK cells mediated anti-tumor immunity

Schisandrin B induces HepG2 cells pyroptosis by activating NK cells mediated anti-tumor immunity

  • Toxicol Appl Pharmacol. 2023 Jun 2;116574. doi: 10.1016/j.taap.2023.116574.
Anping Song 1 Tingting Ding 1 Na Wei 1 Jieren Yang 1 Mingyue Ma 1 Shuguo Zheng 2 Huanhuan Jin 3
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, Anhui, China.
  • 2 Department of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, Anhui, China; Laboratory of Pharmacology of Chinese Medicine, School of Pharmacy, Wannan Medical College, Wuhu, Anhui, China. Electronic address: zhengsg2000@163.com.
  • 3 Department of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, Anhui, China; Laboratory of Pharmacology of Chinese Medicine, School of Pharmacy, Wannan Medical College, Wuhu, Anhui, China. Electronic address: huanhuanjin@wnmc.edu.cn.
Abstract

Pyroptosis, an inflammatory programmed cell death, has been suggested as a novel molecular mechanism for the treatment of hepatocellular carcinoma (HCC) with chemotherapeutic agents. Recent studies showed that natural killer (NK) cells could inhibit Apoptosis and regulate the progression of Pyroptosis in tumor cells. Schisandrin B (Sch B), a lignan isolated from Schisandrae chinensis (Turcz.) Baill. (Schisandraceae) Fructus, has various pharmacological activities including anti-cancer effects. The purpose of this study was to investigate the effect of NK cells on Sch B's regulation of Pyroptosis in HCC cells and the molecular mechanisms implicated. The results showed that Sch B alone could decrease cell viability and induce Apoptosis in HepG2 cells. However, Sch B induced Apoptosis in HepG2 cells was transformed into Pyroptosis in the presence of NK cells. The mechanisms underlying NK cell's effect on Pyroptosis in Sch B-treated HepG2 cells was related to its activation of Caspase 3-Gasdermin E (GSDME). Further studies revealed that NK cell induced Caspase 3 activation was derived from its activation of perforin-granzyme B pathway. This study explored the effect of Sch B and NK cells on Pyroptosis in HepG2 cells and revealed that perforin-granzyme B-caspase 3-GSDME pathway is involved in the process of Pyroptosis. These results proposed an immunomodulatory mechanism of Sch B on HepG2 cells Pyroptosis and suggested Sch B as a promising immunotherapy combination partner for the treatment of HCC.

Keywords

Gasdermin E; Hepatocellular carcinoma; NK-92; Pyroptosis; Schisandrin B.

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