Pro-apoptotic organometallic Sn(IV) bis-organosilane benzoate complexes with sustained antiproliferative activity against resistance-like colorectal cancer cells

In particular, Sn(IV)-biSi-2 and Sn(IV)-biSi-3 reduced cell viability to approximately 30% at 0.5 μM after 5 days, whereas at 12.5 μM they reduced viability to about 11% and 7%, respectively. A repeated-treatment assay was used as a phenotypic evaluation of the ability of the compounds to maintain activity after successive exposure cycles, and thus probing the adaptive resistance-like recovery. After three treatment cycles at 0.5 μM, cisplatin-treated cells showed substantial recovery of viability (approximately 71%), while viability remained lower for Sn(IV)-biSi-1, Sn(IV)-biSi-2 and Sn(IV)-biSi-3 (approximately 44%, 23% and 31%, respectively).

Western blot analysis indicated that the most active complexes promoted DNA damage-associated apoptotic signaling, with increased γ-H2AX, p53, cleaved caspase-3 and cleaved PARP. Overall, these results identify Sn(IV)-biSi-2 and Sn(IV)-biSi-3 as potent pro-apoptotic organotin(IV) candidates that sustain antiproliferative activity after repeated exposure in colorectal cancer cells.