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Melatonin induces apoptosis and cell cycle arrest in cervical cancer cells via inhibition of NF-κB pathway

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Abstract

Cervical cancer is the most prevalent cancer in females. Melatonin, a neurohormone has been documented as a promising therapeutic molecule for cervical cancer. However, the underlying molecular mechanism is not known. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). The anti-cancer effect of melatonin was evaluated by MTT assay, cell imaging, colony formation, DAPI, AO/PI, LDH, Flow cytometry, scratch assay, western blot analysis and real-time PCR. Results of DAPI, AO/PI, LDH, and Annexin/PI staining revealed that melatonin induces apoptosis. The results of cell cycle analysis revealed that melatonin arrests the HeLa and SiHa cells in sub-G1 and G1 phases, respectively. Western blot analysis revealed that melatonin downregulated the expression of pro-inflammatory transcription factor, NF-κB and the expression of COX-2 protein, a key mediator in cell proliferation. In addition, melatonin downregulated the expression of an invasive marker, MMP-9, an antiapoptotic protein, Bcl-2, and upregulated the expression of pro-apoptotic protein, Bax at both transcriptional and translational levels. Overall, the results suggest that melatonin exhibited strong anti-cancer therapeutic potential against human cervical cancer cell line progression possibly through inhibition of NF-κB signalling pathway.

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Acknowledgements

The authors are also thankful to Dr. Rahul Kumar Singh, Department of Zoology, BHU for providing Chemi-Doc facility. We are also thankful to Interdisciplinary School of Life Sciences (ISLS), BHU for flow cytometry and real-time PCR facilities.

Funding

The authors are thankful to the Indian Council of Medical Research (ICMR), New Delhi (ICMR Adhoc Project P-14/267) for the financial assistance to Dr. Sanjeev Kumar Yadav. The JRF fellowship to Mr. Tarun Minocha from UGC-CAS, Dept of Zoology, BHU is highly acknowledged.

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SKY contributed to the study design. TM and MD performed experiments. SSV, NA and VR performed the statistical analysis. SKY wrote the manuscript. SCG and CH revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sanjeev Kumar Yadav.

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Minocha, T., Das, M., Rai, V. et al. Melatonin induces apoptosis and cell cycle arrest in cervical cancer cells via inhibition of NF-κB pathway. Inflammopharmacol 30, 1411–1429 (2022). https://doi.org/10.1007/s10787-022-00964-6

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  • DOI: https://doi.org/10.1007/s10787-022-00964-6

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