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14 January 2020 : Laboratory Research

[Retracted: 25 Mar 2021] 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

Wang Li1BCDF, Zhou Ping1DEF, Gao Xuemei1ABC, Luo Minglian1BCD, Meng Hongjuan1BCE, He Yi1DEF, Zhu Zhongxiang2ACEG*

DOI: 10.12659/MSM.920248

Med Sci Monit 2020; 26:e920248

Retracted, due to breach of publishing guidelines, following the identification of non-original and manipulated figure images. Reference: Wang Li, Zhou Ping, Gao Xuemei, Luo Minglian, Meng Hongjuan, He Yi, Zhu Zhongxiang: 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. Med Sci Monit 2020; 26:e920248. 10.12659/MSM.920248

Abstract

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 modulating the expressions of CDK-1and Cdc25C, and increase in the levels of p-CDK-1, cyclin-B1, cyclin-A, and p-Cdc25C.

CONCLUSIONS: Sclareol not only induced cytotoxic effects but also enhanced chemosensitivity of human cervical cancer cells towards cisplatin and these effects are mediated via MAPK/ERK signaling pathway, stimulation of apoptosis and S-phase cell cycle arrest.

Keywords: Retracted Publication

Retraction note

Med Sci Monit 2021; 27:e932350     https://medscimonit.com/abstract/index/idArt/932350
 
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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750