A novel tin based hydroxamic acid complex induces apoptosis through redox imbalance and targets Stat3/JNK1/MMP axis to overcome drug resistance in cancer

Free Radic Res. 2021 Dec 6:1-52. doi: 10.1080/10715762.2021.2013480. Online ahead of print.ABSTRACTUndesired toxicity and emergence of multidrug resistance (MDR) are the major impediments for the successful application of organotin-based compounds against cancer. Since oxalyl-bis(N-phenyl)hydroxamic acid (OBPHA) exerts significant efficacy against cancer, we believe that derivatives of OBPHA including organotin molecule can show a promising effect against cancer. Herein, we have selected three previously characterized OBPHA derivatives viz., succinyl-bis(N-phenyl)hydroxamic acid (SBPHA), diphenyl-tin succinyl-bis(N-phenyl)hydroxamic acid (Sn-SBPHA), malonyl-bis(N-phenyl)hydroxamic acid (MBPHA) and evaluated their antiproliferative efficacy against both drug resistant (CEM/ADR5000; EAC/Dox) and sensitive (CCRF-CEM; HeLa; EAC/S) cancers. Data revealed that Sn-SBPHA selectively targets drug resistant and sensitive cancers without inducing any significant toxicity to normal cells (Chang Liver). Moreover, shortening of the backbone of SBPHA enhances the efficacy of the newly formed molecule MBPHA by targeting only drug sensitive cancers. Sn-SBPHA induces caspase3-dependent apoptosis through redox-imbalance in both drug resistant and sensitive cancer. Sn-SBPHA also reduced the activation and expression of both MMP2 and MMP9 without altering the expression status of TIMP1 and TIMP2 in drug resistant cancer. In addition, Sn-SBPHA reduced the activation of both STAT3 and JNK1, the tra...
Source: Free Radical Research - Category: Research Authors: Source Type: research