Abstract

Abstract Cervical cancer remains the leading cause of cancer mortality in females worldwide. Despite significant improvement in treatment modalities, the survival in advanced cervical cancer is still limited, resulting in poor survival. Berberine is an isoquinoline alkaloid isolated from Berberis vulgaris (barberry). Berberine is in focus for its preventive and therapeutic value in different cancers. Here we investigated how berberine modulated DNA damage response and survival pathway in cervical carcinoma cells. We carried out the current study in both HPV-positive and -negative cervical carcinoma cell lines. Our results indicate that berberine induced apoptosis in all the cervical carcinoma cells through activation of both caspase-dependent and -independent pathways. Berberine also induces accumulation of gamma H2AX foci in cervical carcinoma cells, which colocalized with proteins involved in DNA damage response, indicating accumulation of replication stress in berberine-treated cells. Berberine also repressed the proliferative RAS MAPK pathway, thereby reducing the proliferation of cervical carcinoma cells. Overall our data provide a novel insight into mechanism of berberine action in cervical carcinoma cells and underline its efficacy as a chemoadjuvant in treatment of cervical cancer. Citation Format: Komal Komal, Vidhya Athreyas, Shilpi Chaudhary, Mayank Singh. Berberine induces apoptosis in cervical carcinoma cells by inducing DNA damage and inhibition of RAS MAPK pathway [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B36.

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