Purpose: Evidence suggested that procyanidin compound (PC) could inhibit the progression of cervical cancer (CC); however, the mechanism still remains unclear. We aimed to study the potential mechanism of PC acting on CC cells.
Patients and Methods: After a 24 hr incubation of lipopolysaccharide (LPS) (1 μg/mL), human CC SiHa and HeLa cells were cultured with various concentrations (20, 40, and 80 μg/mL) of PC for 24 hrs, then the cell viability was detected using Cell Counting Kit-8 (CCK-8). The migration and invasion abilities were assessed by scratch and Transwell assays. Apoptosis and cell cycle were detected using flow cytometry. Real-time quantitative PCR (RT-qPCR) and Western blot were used for expression analysis of the inflammatory cytokines. The pathway components were measured to evaluate the involvement of toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR4/NF-κB) pathway.
Results: PC inhibited the LPS-primed cell viability in a dose-dependent manner. After PC treatment, cell migration and invasion were inhibited, cell number at the G2/M phase was increased. The CC cell apoptosis was triggered through upregulating levels of cleaved caspase-3 and Bax and downregulating the level of B-cell lymphoma 2 protein. A significant reduction was shown in the levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α. Furthermore, a remarkable reduction in the ratio of TLR4 and the p-P65/t-P65 and in the progression of P65 translocation into the nucleus was observed.
Conclusion: Our results revealed that the inhibitory effect of PC on CC cell proliferation relies on the induction of apoptosis and inhibition of inflammatory cytokines.
Keywords: apoptosis, cell cycle, inflammatory cytokines, P65-NF-κB translocation