Effects of Sinapic Acid Combined with Cisplatin on the Apoptosis and Autophagy of the Hepatoma Cells HepG2 and SMMC-7721

Abstract

Sinapic acid (Sa) is a small-molecule phenolic acid compound predominant in fruits, vegetables, and grains. This study investigated the antitumor effects of cisplatin (DDP) combined with Sa (Sa/DDP) on the hepatic cancer cells (HCC), HepG2 and SMMC-7721. The HepG2 and SMMC-7721 cells were treated with Sa or Sa/DDP, and the cell proliferation and cell cycle were detected using the MTT assay. The cell migration was detected using the transwell and scratch assays, while apoptosis and autophagy were detected using Hoechst, MDC, and Annexin V-FITC/PI staining. The protein expression was quantitated using the western blot. Sa/DDP was found to not only inhibit cancer cell proliferation and migration but also induce cell apoptosis. Simultaneously, the Sa/DDP combination was found to activate autophagy, and the HCQ autophagy inhibitor enhanced the apoptosis in the Sa/DDP-induced liver cancer cells. The combined use of Sa and DDP makes it an attractive adjuvant therapy strategy for tumors, establishing the prospect of phenolic acid compounds for the adjuvant treatment of hepatocellular carcinoma.

Mechanisms involved in the anticancer effects of sinapic acid

“…The autophagy inducing effect of SA has been reported by Zhao et al (2021) in HepG2 and SMMC-7721 cells. MDC staining for autophagy showed increased number of green granular structures in cytoplasm and nucleus area of both SA along with cisplatin treated HepG2 and SMMC-7721 cells compared to the untreated cells.…”

“…The findings of the study showed that SA induced an early G0/G1 phase arrest in Hep-2 cells in a dose-dependent manner. Zhao et al (2021) found that SA induced G2/M phase cell cycle arrest in Hep G2 and SMMC-7721 cell lines. The percentage of apoptotic cells of HepG2 cells and SMMC-7721 cells in G2/M phase treatment increased from 12.79 ± 0.89% in control to 22.60 ± 2.26% and 26.00 ± 1.30% after SA along with cisplatin treatment.…”

“…A number of studies have demonstrated that SA can inhibit cell proliferation in prostate cancer (Eroglu et al 2017), liver cancer (Zhao et al 2021), breast cancer (Raj Preeth et al 2019), pancreatic cancer (Huang et al 2021) and myeloid leukemia (Rajendran et al 2017) and induce apoptosis in cell line models. Badr et al (2019) studied the effect of free and nano-capsulated SA on human lung (A549) and colon cancer (Caco-2) cell lines.…”

“…SA-treated cells showed significant membrane blebbing, chromatic condensation, and innumerable micronuclei in cells indicating apoptosis. The apoptotic inducing effect of cisplatin combined with SA on the hepatic cancer cells (HCC) HepG2 and SMMC-7721 were investigated by Zhao et al (2021). SA dose dependently induced apoptotis in both HepG2 and SMMC-7721 cell lines.…”

“…SA acts in collaboration with other chemotherapeutic agents to improve treatment sensitivity. A study investigated the anticancer effects of cisplatin combined with SA against hepatic cancer cells (Zhao et al 2021). SA in combination with cisplatin was found to effectively induce apoptosis, autophagy and prevented cell proliferation.…”