Naturally Occurring Sclareol Diterpene Augments the Chemosensitivity of Human Hela Cervical Cancer Cells by Inducing Mitochondrial Mediated Programmed Cell Death, S-Phase Cell Cycle Arrest and Targeting Mitogen-Activated Protein Kinase (MAPK)/Extracellular-Signal-Regulated Kinase (ERK) Signaling Pathway

作者：Wang Li, Ping Zhou, Gao Xue-mei, Minglian Luo, Meng Hongjuan, Yi He, Zhu Zhongxiang · 发表于：Medical Science Monitor · 年份：2020 · DOI：10.12659/msm.920248 · 被引用次数：10 · 研究领域：Ginseng Biological Effects and Applications、Biological Activity of Diterpenoids and Biflavonoids、Chromatography in Natural Products

BACKGROUND Cervical cancer is a major threat to female health worldwide. This study was performed to study the anticancer potential of sclareol and as a chemo-sensitizing agent against human cervical cancer cells along with evaluating its effects on apoptosis, cell cycle arrest, and MAPK/ERK signaling pathway. MATERIAL AND METHODS MTT assay was performed to check cell viability, morphological changes were observed through phase-contrast microscopy, DAPI (4',6-diamidino-2-phenylindole) staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assays were performed to evaluate apoptotic effects; MMP (matrix metalloproteinase) and cell cycle analysis were examined through flow cytometry. Western blotting analysis was performed to check the protein expressions of MAPK/ERK signaling pathway and apoptosis proteins. RESULTS Results depicted that both sclareol and cisplatin induced cytotoxic effects individually but when used in combination, it led to much more pronounced cytotoxic effects indicating a synergistic effect of sclareol on cisplatin. Sclareol treatment led to significant decrease in the levels of p-MEK and p-ERK. Significant morphological changes (including chromatin condensation, nuclear fragmentation) in cervical cancer cells were seen after treatment. Western blot showed significant alterations including increase in BAX and decrease in BCL-2 levels. An increase in the S-phase cells, indicating cell cycle arrest at S-phase was seen along with m...