Procyanidin Compound (PC) Suppresses Lipopolysaccharide-Induced Cervical Cancer Cell Proliferation Through Blocking the TLR4/NF-κB Pathway
Authors Yang H, Fang Z, Qu X, Zhang X, Wang Y
Received 8 August 2019
Accepted for publication 20 November 2019
Published 22 January 2020 Volume 2020:12 Pages 497—509
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Ahmet Emre Eskazan
Haiyan Yang,* Ziyu Fang,* Xiaoli Qu, Xiaoli Zhang, Yifeng Wang
Department of Obstetrics and Gynecology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaoli Qu
Department of Obstetrics and Gynecology, Fourth Affiliated Hospital of Guangxi Medical University, No. 1 Liushi Road, Yufeng District, Liuzhou, Guangxi 545005, People’s Republic of China
Tel +86 772-3817070
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
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