Repurposing of Alexidine Dihydrochloride as an Apoptosis Initiator and Cell Cycle Inhibitor in Human Pancreatic Cancer

Abstract

Background: Highly aggressive and resistant to chemotherapy, pancreatic cancers are the fourth leading cause of cancer-related deaths in the western world. The absence of effective chemotherapeutics is leading researchers to develop novel drugs or repurpose existing chemicals. Alexidine Dihydrochloride (AD), an orally bioavailable bis-biguanide compound, is an apoptosis stimulating reagent. It induces mitochondrial damage by inhibiting a mitochondrial-specific protein tyrosine phosphatase, PTPMT1. The aim of this study was to test AD as a novel compound to induce apoptosis in a human pancreatic adenocarcinoma cell lines, Panc-1, MIA PaCa-2, AsPC-1, and Psn-1.

Methods: After the IC50 value of the AD was determined by cytotoxicity assay, apoptosis was observed by a variety of methods, including the detection of early apoptosis marker Annexin V and the proteomic profile screening by apoptosis array. Multicaspase and mitochondrial depolarization were measured, and changes in the cell cycle were analyzed.

Results: AD is found to initiate apoptosis by activating the intrinsic pathway and inhibit the cell cycle in pancreatic cancer cell lines.

Conclusion: In conclusion, considering its anti-cancer properties and bioavailability, Alexidine dihydrochloride can be considered as a potential candidate against pancreatic adenocarcinomas.

Keywords: Cancer; alexidine dihydrochloride; apoptosis; cell cycle; chemotherapy; pancreatic adenocarcinoma.