Anticancer Activity of Apaziquone in Oral Cancer Cells and Xenograft Model: Implications for Oral Cancer Therapy.

Abstract

Oral squamous cell carcinoma (OSCC) patients diagnosed in late stages have limited chemotherapeutic options underscoring the great need for development of new anticancer agents for more effective disease management. We aimed to investigate the anticancer potential of Apaziquone, [EOquin, USAN, E09, 3-hydroxy-5- aziridinyl-1-methyl-2(1H-indole-4,7-dione)-prop-β-en-α-ol], a pro-drug belonging to a class of anti-cancer agents called bioreductive alkylating agents, for OSCC. Apaziquone treatment inhibited cell proliferation and induced apoptosis in OSCC cells in vitro. Apaziquone treated OSCC cells showed increased activation of Caspase 9 and Caspase 3, and Poly (ADP ribose) polymerase (PARP) cleavage suggesting induction of apoptosis by apaziquone in oral cancer cells. Importantly, apaziquone treatment significantly reduced oral tumor xenograft volume in immunocompromised NOD/SCID/Crl mice without causing apparent toxicity to normal tissues. In conclusion, our in vitro and in vivo studies identified and demonstrated the pre-clinical efficacy of Apaziquone, as a potential novel anti-cancer therapeutic candidate for oral cancer management.

• Authors: Gunjan Srivastava, Raj Thani Somasundaram, Paul G Walfish, Ranju Ralhan
• Journal: PloS one (PLoS One) Vol. 10 Issue 7 Pg. e0133735 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26208303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Antineoplastic Agents
• Aziridines
• Indolequinones
• apaziquone

Topics

• Animals
• Annexin A5 (metabolism)
• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Aziridines (administration & dosage, pharmacology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Humans
• Indolequinones (administration & dosage, pharmacology)
• Mice
• Mouth Neoplasms (drug therapy, metabolism, pathology)
• Tumor Burden
• Xenograft Model Antitumor Assays