Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells

Yuan Wang,Jun Wei,Yaqin Wei,Xu Su,Yunli Zhao,Qingjie Peng,Huazhang Wu,Gaofeng Liu,Mingxiu Duan,Nannan Dong

doi:10.1038/s41598-021-81815-2

Yuan Wang, Jun Wei + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-81815-2

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Abstract

Sulforaphane (SFN) extracted from broccoli sprout has previously been investigated for its potential properties in cancers, however, the underlying mechanisms of the anticancer activity of SFN remain not fully understood. In the present study, we investigate the effects of SFN on cell proliferation, cell cycle, cell apoptosis, and also the expression of several cell cycle and apoptosis-related genes by MTT assay, flow cytometry and western blot analysis in gastric cancer (GC) cells. The results showed that SFN could impair the colony-forming ability in BGC-823 and MGC-803 cell lines compared with the control. In addition, SFN significantly suppressed cell proliferation by arresting the cell cycle at the S phase and enhancing cell apoptosis in GC cells in a dose-dependent manner. Western blot results showed that SFN treatment significantly increased the expression levels of p53, p21 and decreased CDK2 expression, which directly regulated the S phase transition. The Bax and cleaved-caspase-3 genes involved in apoptosis executive functions were significantly increased in a dose-dependent manner in BGC-823 and MGC-803 cells. These results suggested that SFN-induced S phase cell cycle arrest and apoptosis through p53-dependent manner in GC cells, which suggested that SFN has a potential therapeutic application in the treatment and prevention of GC.

Highlights

Sulforaphane is an isothiocyanate compound mainly derived from cruciferous vegetables such as broccoli, Brussels sprouts and cabbage[1]
The focus of this study was to evaluate the effects of SFN on cell cycle and apoptosis in gastric cancer (GC) cells
Our study showed that SFN induced S phase arrest in BGC-823 and MGC-803 GC cells, the results were consistent with previous reports by Juengel et al, that SFN induces S phase arrest in kidney carcinoma Caki-1 c ell[48]

Summary

Introduction

Sulforaphane is an isothiocyanate compound mainly derived from cruciferous vegetables such as broccoli, Brussels sprouts and cabbage[1]. SFN has been found to exert anticancer effects by inhibiting cell proliferation[6], promoting apoptosis[7], inhibiting metastasis[8] and anti-angiogenesis p roperties[9] in cancer cells. In China, there are 679,000 new cases and 498,000 deaths of GC in 2015, both of which ranked second in malignant tumors[12]. Several studies have demonstrated that SFN inhibits the proliferation and promotes apoptosis of GC cells through various mechanism and t argets[24,25,26,27]. Novel mechanisms involved in SFN-induced apoptosis and cell cycle arrest in GC, our studies will assist us in developing new anticancer drugs for GC patients

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Conclusion