Cell and Molecular Level Understanding of the Potential Anticancer Properties of Azadirachta indica A. Juss. Stem Bark Against Cervical Cancer

Kumar, Saurav (2024) Cell and Molecular Level Understanding of the Potential Anticancer Properties of Azadirachta indica A. Juss. Stem Bark Against Cervical Cancer. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Saurav Kumar (17IP029)) 17IP029.pdf - Submitted Version Restricted to Repository staff only Download (13MB)

Abstract

Despite being a preventable disease, cervical cancer remains a significant cause of mortality in women worldwide, specifically in Asian countries. Lack of effective screening and medical facilities in developing countries leads to late-stage diagnosis, ultimately contributing to high mortality. Treatment options at advanced stages include surgery in combination with a high dose of CT and RT, which is often associated with multiple side effects. Moreover, the poor survival rate of cervical cancer patients reflects the ineffectiveness of these therapies. Hence, there is a constant quest to find or develop new therapeutic drugs. Medicinal plants have remained an inspiration and basis for designing new anticancer drugs. Among various medicinal plants, Azadirachta indica A. Juss. (Neem) has indispensable medicinal importance in Ayurveda, Unani, Homoeopathy, and modern medicine. Numerous studies have also validated the traditional use of neem extracts to prevent and treat different cancers. The present study investigated the anticancer potential of methanolic neem stem bark extract (MNBE) and its derived fraction against cervical cancer. The study showed that crude MNBE could inhibit the growth of cervical cancer cells and induce apoptosis. Furthermore, MNBE could restrict the migration of cervical cancer cells. Fractionation of neem extract using dichloromethane as solvent revealed nine fractions (F1-F9), out of which F2 showed the strongest cytotoxic activity. Further studies revealed that F2 induced ER stress and oxidative stress in cervical cancer cells, which resulted in cancer cell death. More importantly, both MNBE and F2 exhibited minimal toxicity against normal cells, demonstrating their specificity towards cancer cells. Analytical characterization of F2 showed the presence of terpenoids and flavonoids. Using 3D cervical tumor spheroids as an in vivo model, our study demonstrated the antitumor potential of MNBE and F2 against cervical cancer. Hence, this study provides substantial evidence to utilize MNBE and F2 as a source to develop novel anticancer drugs against cervical cancer.

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