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

Inflammopharmacology. 2022 Aug;30(4):1411-1429. doi: 10.1007/s10787-022-00964-6. Epub 2022 Apr 17.

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.

Keywords: Apoptosis; Cervical cancer; Melatonin; NF-κB signalling; Oncogenesis.

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Melatonin* / pharmacology
  • Melatonin* / therapeutic use
  • NF-kappa B / metabolism
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Apoptosis Regulatory Proteins
  • NF-kappa B
  • Melatonin