Sulforaphane induces pyroptotic cell death via caspase signaling pathway in Hepatocellular Carcinoma (HCC): an alternative immuno-therapeutic approach


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Kanipandian Nagarajan1,Deyu Li2,Dongxiao Li3
1Henan Provincial People’s Hospital/Henan University, Zhengzhou, China,2Henan Provincial People's Hospital, Zhengzhou, China,3Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Abstract

Background

Cancer can be considered the consequence of genetic alterations that lead to a normal cell being transformed into a malignant one while avoiding cell death—atypical characteristics of tumor development. Although a large number of genomics and epigenetic alterations have been identified in cells undergoing apoptotic, autophagic or necrotic cell death, the treatment of cancer remains challenging.

Defect in the caspases gene expression has been discovered in prostate and gastric tumor progression. However, the role of the signaling mechanism of pyroptosis in human hepatocellular carcinoma (HCC) remains unexplored. Hence, the molecular mechanisms for the Caspases activation in tumor tissues are yet to be exploited extensively. The goal of this study was to reveal the molecular mechanism of pyroptosis activation in HCC cells by an anticancer drug. 

Method

Three different cell lines were used Chang liver, Hep G2 and Huh-7. The cells were treated with Sulforaphane (SFN) which is the anticancer compound and further In vitro cell morphology, MTT, Transwell assay for cell migration, RT-PCR, Immunofluorescence and Western blot assays were used.

Results

Administration of sulforaphane caused the decreased cell number, cell swelling inhibited the viability, migration and invasion capacity of HepG2 and Huh-7 cells. The inhibitory concentration of sulforaphane against Hep-G2 (7.5 µM/ml), Huh-7 (7.5 µM/ml) and Chang liver normal (12.5 µM/ml) concentration were recorded. Interestingly, immunofluorescence and Western blot assays clearly demonstrated the up-regulation of caspase 3 in the treated HCC cells when compared with control cells. Here we report that gasdermin D (GSDMD) is a crucial component of inflammasomes and observed the presence of GSDMD protein in sulforaphane-induced HCC cells.

Conclusion

This current investigation was aimed to explore the latest ideology about pyroptosis and its new exciting role in inducing cancer cell death in HCC. Taken together, these data provide new insights into the molecular mechanisms for the induction of pyroptosis-mediated cancer cell death for cancer therapy.