Salinomycin mediated therapeutic targeting of circulating stem like cell population in oral cancer

Area of Science:

• Oncology
• Cancer Stem Cell Biology
• Pharmacology

Background:

• CD44+ circulating tumor stem cells (CTSCs) are linked to oral cancer aggressiveness, resistance, and poor prognosis.
• Targeting CTSCs offers a novel therapeutic strategy to improve patient outcomes.

Purpose of the Study:

• To evaluate Salinomycin as a potential therapeutic agent against CD44+ CTSCs in oral cancer.
• To investigate the mechanisms underlying Salinomycin's effect on chemo-resistant oral cancer stem cells.

Main Methods:

• Immuno-magnetic sorting of CD44+ cells from oral cancer patients.
• Assessment of cytotoxic effects of Salinomycin, 5FU, and Cisplatin.
• Analysis of apoptosis, cell cycle, signaling pathways (MAPK/PI3K), and gene expression (CD44v6, Nanog, AKT1, CDKN2A, β-catenin) using Muse™ flow cytometry and Real-Time PCR.

Main Results:

• Salinomycin exhibited significant dose- and time-dependent cytotoxicity against CD44+ oral cancer cells.
• Salinomycin induced G2/M cell cycle arrest and programmed cell death.
• Salinomycin treatment modulated the expression of key genes including CD44v6, Nanog, AKT1, CDKN2A, and β-catenin, while inhibiting MAPK/PI3K pathways.

Conclusions:

• Salinomycin demonstrates potent anti-cancer activity by targeting chemo-resistant CD44+ circulating tumor stem cells.
• Salinomycin effectively attenuates the proliferation and survival of these critical cancer stem cells.
• This study establishes Salinomycin as a promising therapeutic candidate for overcoming chemo-resistance in oral cancer.