World Journal of
Pharmaceutical and Life Sciences

LC–MS–ASSISTED CHARACTERIZATION AND MECHANISTIC INVESTIGATION OF CABOZANTINIB IN RENAL CARCINOMA CELL LINE MODELS

Dr. Syed Ahmed Hussain*, Nada Ahmed Al Amoodi, Ghousia Begum, Fariya Sultana, Bilquis Begum, Somabatthini Shruthi, Ayesha Ayub Khan, Muskan Khatoon

ABSTRACT

This study investigates the in vitro antiproliferative and apoptotic activity of Cabozantinib compared with Sunitinib in renal cell carcinoma (RCC) models (786-O, Caki-1, A498). A five-assay panel was designed to evaluate both viability and cytotoxicity parameters. Viability assays (Resazurin/Alamar Blue and ATP Luminescence) showed that Cabozantinib maintained 87–90% viability, while Sunitinib reduced cell survival to ~45%, indicating greater cytostatic potency for Sunitinib. Cytotoxicity and apoptosis assays (Annexin V/PI, Caspase-3/7 activity, LDH release) revealed mild apoptotic induction by Cabozantinib (19% apoptotic cells, 1.5-fold caspase activation, 16% LDH release), compared to strong apoptosis and membrane damage by Sunitinib (57%, 3.5-fold, 58%). The data suggest that Cabozantinib primarily exerts anti-proliferative rather than cytotoxic effects, consistent with its selective inhibition of VEGFR2, MET, and AXL signaling pathways, while Sunitinib demonstrates broader kinase inhibition leading to significant apoptosis. Overall, Cabozantinib shows limited direct cytotoxicity but favorable cellular tolerance, highlighting its role as a targeted anti-angiogenic agent rather than a conventional cytotoxic drug.

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