Evaluation of anticancer activity of Gmelina asiatica leaves, in-vitro and in-silico studies

Abstract

Cervical cancer poses a major threat to women’s health worldwide, constituting the fourth most prevalent cancer among the female population. High-risk variants of human papillomavirus (HPV) with its oncogenic proteins are a necessary cause of cervical cancer. Due to the resistance of cancer cells to the current treatment, there is a need for new medicines with new strategies to treat cervical cancer. Gmelina asiatica Linn. is a medicinal plant with various traditional uses and biological activities. Its anticancer potential against breast cancer and lymphoma has been demonstrated in the literature. In view of this, our study aims to investigate the anticancer activity of Gmelina asiatica leaves against cervical cancer. Various extracts of Gmelina asiatica leaves were prepared by soxhletation and maceration methods. The cytotoxic activity of the extracts was evaluated through in-vitro studies against SiHa cell line using MTT assay and fluorescence imaging. The most potent extract (GAME) phytochemical profile was analysed by UHPLC-HRMS. Further, in-silico studies were performed on its phytoconstituents against E6 oncoprotein, and the DFT studies were conducted on the active component to assess the physicochemical properties. In-vitro studies revealed that methanolic extract (GAME) showed the highest inhibition on the SiHa cell line compared to the other extracts and the control (p < 0.0001). In-silico studies indicated high affinity with stable interaction of the compound 5 (JC5ABDR) at E6 binding sites. This study revealed the importance of Gmelina asiatica plant as a potential source of anticancer molecules with a specific mode of action against cervical cancer.

Communicated by Ramaswamy H. Sarma

Keywords:

• Gmelina asiatica
• cervical cancer
• E6 oncoprotein
• SiHa cell line
• E6/E6AP/p53 complex
• DFT studies

Acknowledgments

The author Rasha Ksirri is grateful to Indian Institute of Technology (BHU), Varanasi for providing lab facilities to perform this project. Damascus University, Syria and Indian Council for Cultural Relations (ICCR), India are greatly acknowledged for providing a scholarship and opportunity to study in India. The author is thankful to CDC-BHU for UHPLC-HRMS analysis.

Authors’ contributions

Rasha Ksirri: conceptualization, design, methodology, investigation, writing, review, and editing of original manuscript. Kancharla Bhanukiran: helped in in-silico studies, suggestion, review, and editing. Swapan Maity and Pralay Maiti: helped in in-vitro studies. Siva Hemalatha: design, methodology, supervision, suggestion, review, and editing.

Disclosure statement

The authors declare that there is no conflict of interest.

Data availability statement

Data will be made available on request.

Additional information

Funding

This research received no specific grant from any funding agency.