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Demethylation of CADM1 and SOCS1 using capsaicin in cervical cancer cell line

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Abstract

Cervical cancer is one of the leading causes of women’s mortality in developing countries. The prevalence of cervical cancer is higher in developing countries like India and continents like Africa. Hyper-methylation of tumor suppressor genes through human papillomavirus (HPV) infection is known to be one of the major causes of cervical cancer. The promoter hypermethylation of the cell adhesion molecule 1 (CADM1) and suppressor of cytokine signalling (SOCS1) genes due to DNMT1 overexpression leads to their epigenetic silencing followed by gene repression causing cervical cancer. In silico study on the inhibition effect of capsaicin on DNMT1 was simulated by different servers. The binding energy was observed to be −7.8 kcal/mol. In vitro studies on the effect of capsaicin on aberrant methylation of CADM1 and SOCS1 were performed on the adenocarcinoma cervical cancer cell line, HeLa. The IC50 of capsaicin was observed to be 160 μM through crystal violet assay. DNA methylation of the CADM1 and SOCS1 was analyzed by methylation-specific PCR along with their reversal using capsaicin (20 μM) by treating the cells for 72 h and 6 days. In silico results suggested that capsaicin has an inhibitory effect on DNMT1, which regulates DNA methylation leading to the hypermethylation of CADM1 and SOCS1 genes. The in vitro studies suggested that hypermethylation leads to the inhibition of CADM1 and SOCS1 expression, which could be reversed using capsaicin with visible changes in methylation-specific and unmethylation-specific bands in MS-PCR, respectively. The present study shows the reversal of methylation of CADM1 and SOCS1 after 72 h which showed a further increase in case of 6 days of treatment using 20 μM capsaicin, which makes capsaicin a potent candidate for causing demethylation of CADM1 and SOCS1 genes that may lead to the reactivation of the downregulated gene.

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In texts, all the accessible websites and organizations have been provided. The authors declare that all data were generated in-house, and no paper mill was used.

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Acknowledgements

The authors acknowledge the help and facilities provided by Delhi University, India, and Sharda University, India.

Author information

Author notes

  1. Mahek Sharan and Meenakshi Jha contributed equally to the paper.

Authors and Affiliations

  1. Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Mahek Sharan

  2. Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, 201310, India

    Mahek Sharan, Niraj Kumar Jha, Saurabh Kumar Jha & Abhimanyu Kumar Jha

  3. Department of Biotechnology, Amity University, Raipur, Chhattisgarh, India

    Meenakshi Jha & Sushma Chauhan

  4. Department of Zoology, Delhi University, Delhi, India

    Rishima Chandel, Saima Syeda & Anju Shrivastava

  5. A.P.J Abdul Kalam University, Lucknow, Uttar Pradesh, India

    Runjhun Mathur

  6. Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, 248007, India

    Niraj Kumar Jha & Saurabh Kumar Jha

  7. Department of Biotechnology Engineering and Food Technology, Chandigarh University, Mohali, 140413, India

    Niraj Kumar Jha & Saurabh Kumar Jha

  8. Laboratory of the Oncology Unit, Dr. B.R.A, Institute Rotary Cancer Hospital, AIIMS, Delhi, India

    Harsh Goel

  9. Department of Molecular Biology and Genetics, Gujarat Biotechnology University, Gandhinagar, Gujarat, India

    Sudheer Pamidimarri

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  1. Mahek Sharan
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Contributions

AKJ and AS conceived and designed the research. MS and MJ conducted experiments. SS, RM, and RC contributed to analytical tools. MS and MJ wrote the manuscript. HG, SC, and SP contributed to the image analysis. AKJ, NKJ, and SKJ analyzed the data. All authors read and approved the manuscript. The authors declare that all data were generated in-house, and no paper mill was used.

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Correspondence to Abhimanyu Kumar Jha.

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Sharan, M., Jha, M., Chandel, R. et al. Demethylation of CADM1 and SOCS1 using capsaicin in cervical cancer cell line. Naunyn-Schmiedeberg's Arch Pharmacol 396, 649–657 (2023). https://doi.org/10.1007/s00210-022-02340-1

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