IOX-101 reverses drug resistance through suppression of Akt/mTOR/NF κB signaling in cancer stem cell like, sphere forming NSCLC cells.

In this study we used drug resistant lung cancer stem like cells (A549-CS) to compare the efficacy of standard drugs like cisplatin (DDP) and gemcitabine (GEM) with a novel arylidene derivative IOX-101. A549-CS was derived from regular A549 cells by growing in special media. Resistance proteins were detected using Western Blotting. Cell proliferations were assessed by MTT assay. Cytokine release was enumerated using ELISA. Effect of drugs on apoptosis and cell cycle were studied with flow cytometry protocols. Apoptosis related proteins, caspases and other signaling protein expressions like Akt, mTOR were assessed by Western Blotting. Expression of CD 133 and NFκB phosphorylation was assessed using flow cytometry. A549-CS showed significant increase of CD 133 expression in comparison with A549 cells. Expression of resistance markers like MDR-1, LRP and GST-∏ were detected in A549-CS. While DDP, GEM had relatively lower efficacy in A549-CS, IOX-101 inhibited the proliferation of both A549 and A549-CS with GI50 values of 268 and 296.5 nM respectively. IOX-101 increased sub G0 phase in cell cycle of A549-CS and increased the percentage of apoptotic cells. Western Blot analysis revealed activation of caspases, Bax and reduction of Bcl-2 levels. Further mechanistic investigation revealed IOX101 to deactivate Akt, mTOR and NFκB signaling in A549-CS cells. Additionally, IOX-101 treatment to A549-CS also reversed MDR-1, LRP expressions. Collectively, our results demonstrate effica...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research