Synergistic action of Cisplatin and 9-Phenyl acridine in A375 cells

ABSTRACT

Cisplatin is a widely used chemotherapeutic drug and its potency lead to treatment of different types of cancer. Cisplatin discovery has led to the perception that platinum (II) compounds can be potent anticancer drugs that can successfully use in the treatment of cancers like cancer of bones, muscles, soft tissue, blood, etc. In spite of having such a broad spectrum of anticancer activity, these platinum compounds are poisons, become resistance to different cancers and produce severe side effects. So, cisplatin is often used in combination with other chemotherapeutic agents like PARP inhibitors to increase its efficacy at lower doses. In this report, we present our findings on the effect of 9-Phenyl acridine (ACPH) on cisplatin toxicity in A375 cells. ACPH could sensitize killing of both exponential and density inhibited A375 human melanoma cells. Compared to cisplatin alone, co-treatment of cisplatin with ACPH resulted in an increase in DNA damage, ROS generation and depletion of GSH level in treated cells. Apoptotic death was also enhanced. ACPH possibly potentiated the effects of cisplatin through the inhibition of PARP1 activity.