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, therapy resistance, and recurrence. Due to CSCs’ resistance, it’s demanded to develop drugs having appropriate efficacy. Despite cisplatin is a potent antitumor agent widely used in the treatment of different cancers, its severe side effects and resistance remain a challenge in the clinic. Research has shown that platinum (IV) has considerably fewer side effects and drug resistance. In this study, toxicity and effectiveness of [Pt(dpyam)Cl4] where dpyam is 2,2'-dipyridylamine, as a platinum (IV) agent, has been investigated to find a reliable alternative for cisplatin. To this aim, cancer stem-like cells (CS-LCs) with CD44+/CD133+ phenotype were isolated from HT1080 cells. EJ138, HT1080, and its CS-LCs 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 in CS-LCs. Although toxicity results were in favor of cisplatin, the anti-cancer activity of the synthesized Pt (IV) complex was also considerable. Regarding other studies that proposed high selective toxicity of Pt (IV), they could be a volunteer for additional improvements.

Keywords

• Cancer stem-like cells
• Platinum (IV)
• Cisplatin
• Cytotoxicity
• Self-renewal