World Journal of
Pharmaceutical and Life Sciences

LC–MS–GUIDED METABOLIC AND MECHANISTIC ASSESSMENT OF FLUDARABINE IN PANCREATIC CANCER CELL LINE MODELS

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

ABSTRACT

This study investigates the in vitro antitumor potential of Fludarabine compared with Gemcitabine in pancreatic cancer cell line models (PANC-1, MIA PaCa-2, AsPC-1). A five-assay panel was designed to measure both viability and cytotoxicity parameters. Cell viability assays (Resazurin/Alamar Blue and ATP Luminescence) showed that Fludarabine retained 79–81% viability, indicating weak antiproliferative effects relative to Gemcitabine (44–39%). Cytotoxicity assays revealed moderate apoptotic activity for Fludarabine (24% apoptotic cells, 1.9-fold caspase activation, 22% LDH release), significantly lower than Gemcitabine’s strong apoptosis induction (59%, 3.7-fold, and 60%, respectively). These findings demonstrate that Fludarabine exerts limited cytotoxic and apoptotic effects in pancreatic cancer cells, possibly due to insufficient nucleoside transport or poor DNA incorporation efficiency in non-hematologic tumors. In contrast, Gemcitabine displayed robust cytotoxic performance, validating the assay platform’s sensitivity. Overall, Fludarabine shows modest activity but favorable cytocompatibility, suggesting potential utility as a low-toxicity adjunct or chemosensitizer rather than a standalone cytotoxic agent for pancreatic cancer therapy.

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