Resveratrol inhibits oral squamous cell carcinoma cells proliferation while promoting apoptosis through inhibition of CBX7 protein

Abstract

As a natural compound, resveratrol (Res) is confirmed to be promising drug for the treatment of malignant tumors. Therefore, our study aimed to observe the impacts of Res on the proliferation and apoptosis of oral squamous cell carcinoma cells (HSC-3 cells) as well as the mechanism involving chromobox protein homolog 7 (CBX7) signal transduction. HSC-3 cells were treated with Res, Akt agonist (AL3818) and p16 inhibitor (SC79), and transfected with CBX7 mimics and inhibitor plasmids. The CCK-8 assay was used to detect cell proliferation, flow cytometry was performed to assess cell cycle and apoptosis, and cell colonies and histone DNA level were also measured. Western blot analysis was used to determine the expression levels of related proteins. HSC-3 cells showed decreased cell proliferation, colonies, BrdU-counled cells and increased apoptosis, histone DNA level, the activities of caspase-3 and caspase-9 when treated with Res. Western blot analysis revealed elevated Cle-PARP and Cle-caspase 3 expression and reduced t-PARP expression in HSC-3 cells treated with Res compared with control. AL3818 and SC79 could decrease the inhibitory effects of Res on the growth of HSC-3 cells. Furthermore, CBX7 overexpression could also partly reverse the roles of Res in the growth of HSC-3 cells, and Akt and p16 signal transduction. Our results demonstrate that Res suppresses the proliferation, and induces the apoptosis of oral squamous cell carcinoma cells through the inhibition of CBX7/Akt and the activation of p16 cascades.

Resveratrol acts via melanoma-associated antigen A12 (MAGEA12)/protein kinase B (Akt) signaling to inhibit the proliferation of oral squamous cell carcinoma cells

“…Furthermore, resveratrol has been demonstrated to overcome cetuximab-resistance in OSCC by targeting urokinase-type plasminogen activator receptor [43]. Additionally, extensive observations have also reported that resveratrol suppressed the growth of OSCC cells by regulating chromobox protein homolog 7 (CBX7) signal transduction, inducing mitochondrial apoptosis and G2/M phase cell cycle arrest, and inhibiting epithelial-mesenchymal transition [44][45][46]. However, the association among resveratrol and MAGEA12 has not been reported.…”

Research Progress of Resveratrol in Oral Cancer

“…A dose-dependent decrease in cell viability was also observed after treatment of H-357 cells with resveratrol [41]. Chen et al treated HSC-3 cells with different concentrations (0,15,30,60, and 90 μM) at different time points and found that the number of cells in G1 phase increased and cells in S and G2 phases decreased [27]. In conclusion, resveratrol is expected to become a new drug for the treatment of OSCC through the regulation of cell cycle function.…”

“…Resveratrol significantly induced the expression of the proapoptotic gene BAD in OEC-M1 cells [25] , and inhibited thyroid hormone-induced antiapoptotic activity by inhibiting death ligand 1 (PD-L1) expression [26], also inhibited the proliferation and induced apoptosis of oral squamous cell carcinoma cells by inhibiting CBX 7/Akt and activating the p16 cascade [27].…”

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

“…A chimera composed of the CBX5 protein fused to the estrogen receptor-DNA-binding domain and AR-ligand-binding domain is an effective transcriptional inhibitor and participates in the gene silencing effect associated with long-term 4-hydroxytamoxifen (OHT) therapy, inducing drug resistance to OHT (235). Resveratrol inhibits the proliferation of oral squamous cell carcinoma and induces apoptosis by inhibiting CBX7/AKT and activating the p16 signaling pathway (236). The retention of CBX7 decreases lung cancer cell proliferation (at least partially through the downregulation of phosphorylated ERK and phosphorylated p38) and increases the apoptosis rate after irinotecan and etoposide therapy (at least partially through the downregulation of Bcl-2, phosphorylated AKT and phosphorylated JNK) (237).…”