Benzyl isothiocyanate triggers apoptosis by initiating autophagy through the generation of ROS and modulating the MAPK and PI3K-AKT pathway in cervical cancer cells

Benzyl isothiocyanate (BITC), a bioactive compound derived from cruciferous vegetables, has demonstrated antitumor potential against cervical cancer; However, its underlying mechanisms remain obscure. Through in vitro and in vivo experiments, this study focuses on unraveling the mechanisms by which BITC inhibits cervical cancer cell proliferation, with a particular emphasis on the relationship between autophagy and apoptosis regulated by oxidative stress and the critical roles of signaling pathways such as MAPK/PI3K-AKT in this process. The findings reveal that BITC exhibits potent cytotoxicity toward cervical cancer HeLa cells, significantly suppressing HeLa colony formation and migration, and inducing apoptosis and reactive oxygen species (ROS) production. Treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly reduced the proportion of BITC-induced apoptotic cells and the expression of apoptosis-related proteins. Mechanistically, BITC activates the JNK and p38 MAPK pathways while inhibiting the ERK1/2 MAPK and PI3K-AKT axes. However, administration of a JNK inhibitor or ERK/PI3K agonists reversed the BITC-induced expression of autophagy-related protein Beclin 1 and apoptotic protein Cleaved Caspase-3. Additionally, the ROS scavenger N-acetylcysteine abrogated BITC-affected protein expression, including p-JNK, p-ERK, p-PI3K, Beclin 1, and Cleaved Caspase-3. In vivo studies showed that BITC significantly inhibited tumor growth, upregulating the expression of p-JNK, LC3BII/I, Beclin I, Cleaved PARP, and Bax, while downregulating p-ERK, p-AKT, and Bcl-2 proteins. Overall, BITC exerts anti-cervical cancer effects through ROS-driven redox disruption and lethal autophagy induction, modulating MAPK and PI3K-AKT pathways. This finding underscores the potential of BITC for the treatment of cervical cancer.