Alterations in gene promoter methylation and transcript expression induced by cisplatin in comparison to 5-Azacytidine in HeLa and SiHa cervical cancer cell lines

• Published in: Molecular and cellular biochemistry 2015-06, Vol.404 (1-2), p.181-191
• Main Authors: Sood, Swati, Srinivasan, Radhika
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Azacitidine - administration & dosage; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell Proliferation - drug effects; Cells; Cervical cancer; Cisplatin; Cisplatin - administration & dosage; Comparative analysis; CpG Islands - drug effects; DNA methylation; DNA Methylation - drug effects; Drug therapy; Epigenetic inheritance; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genes; Health aspects; HeLa Cells; Humans; India; Life Sciences; Medical Biochemistry; Methylation; Mortality; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Oncology; Promoter Regions, Genetic - drug effects; Squamous cell carcinoma; Synergism; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-015-2377-3

Despite recent advances in treatment, cervical cancer still remains one of the leading causes of cancer related mortality among women worldwide including India. Chemoradiation treatment is the standard-of-care which involves administration of cisplatin, a radiosensitizer along with radiation. The epigenetic changes induced by cisplatin are not known and so we designed this in vitro experimental study. We evaluated the changes induced by cisplatin administration in gene promoter methylation and the transcript levels of set of 7 genes and compared it to the changes induced by 5-Azacytidine, a known demethylating agent in two cervical cancer cell lines: HeLa (adenocarcinoma derived) and SiHa (squamous cell carcinoma derived) cell lines. Overall, there was a pronounced cytotoxic and growth inhibitory effect of both the drugs alone and in combination for both the cell lines which was dose and time dependent. Cisplatin as well as 5-Azacytidine treatment affected gene promoter methylation status resulting in demethylation and re-expression of the genes under investigation which was more pronounced in case of SiHa cells as compared to HeLa cells. Further, both the drugs acted in synergism as evident from their combination treatment. Therefore, at the cellular level, cisplatin and 5-Azacytidine can induce epigenetic changes in gene promoter methylation with altered expression which can have implications for treatment of cervical cancer.