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.

• Authors: Ezgi Kasikci, Esra Aydemir, Bekir M Yogurtcu, Fikrettin Sahin, Omer F Bayrak
• Journal: Anti-cancer agents in medicinal chemistry (Anticancer Agents Med Chem) Vol. 20 Issue 16 Pg. 1956-1965 ( 2020) ISSN: 1875-5992 [Electronic] Netherlands
• PMID: 32384037 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Antineoplastic Agents
• Biguanides
• alexidine

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Biguanides (chemistry, pharmacology)
• Cell Cycle (drug effects)
• Cell Line
• Dose-Response Relationship, Drug
• Drug Repositioning
• Drug Screening Assays, Antitumor
• Humans
• Molecular Structure
• Pancreatic Neoplasms (drug therapy, pathology)
• Structure-Activity Relationship