Anticancer Properties of a New Platinum (IV) Agent on HT1080 Cancer Stem-Like Cells: An in Vitro Study

Abstract

According to the cancer stem cell (CSC) theory, a subpopulation of cells demonstrating stem-like cell properties is responsible for tumorigenicity, self-renewal capacity, therapeutic resistance, and recurrence. Due to the resistance of CSCs, it is necessary to develop drugs with appropriate efficacy. Although cisplatin is a potent antitumor agent widely used in the treatment of different cancers, its severe side effects and resistance remain a challenge in clinical practice. Research has shown that platinum (IV) has considerably fewer side effects and is associated with much less drug resistance. In this study, the toxicity and effectiveness of [Pt(dpyam)Cl4], where dpyam is 2,2'-dipyridylamine as a platinum (IV) agent, was investigated to find a reliable alternative to cisplatin. For this purpose, cancer stem-like cells (CS-LCs) with CD44+/CD133+ phenotype were isolated from HT1080 cells. EJ138, HT1080, and CS-LCs derived from HT1080 cells were selected to compare the effectiveness of Pt (IV) complex versus cisplatin. MTT, apoptosis, and cell cycle analysis were carried out to evaluate drug toxicity. Sphere and colony formation assays confirmed the potentiality of Pt (IV) complex and cisplatin to target stemness characteristics of CS-LCs. Although toxicity results were in favor of cisplatin, the anticancer activity of the synthesized Pt (IV) complex was also considerable. Regarding other studies that proposed high selective toxicity of Pt (IV), it could be a candidate for additional improvements.