Anticancer effect of benzyl isothiocyanate on the apoptosis of human gemcitabine-resistant pancreatic cancer MIA PaCa-2/GemR cells (MIA RG100)

Background: Benzyl isothiocyanate (BITC) is a natural compound found in numerous cruciferous vegetables, and research has indicated that it has diverse biological activities. Isothiocyanate and its derivatives are the major anticancer natural compounds in cruciferous vegetables; these compounds help inhibit tumor cell proliferation through various mechanisms such as promoting tumor cell apoptosis, prompting cycle arrest, and increasing the generation of reactive oxygen species (ROS). Objectives: In human pancreatic cancer, gemcitabine is the first-line treatment; however, pancreatic cancer cells readily develop resistance to gemcitabine. Studies have demonstrated that natural products can promote the effect of gemcitabine and enhance the apoptosis process; however, the relevant mechanism and potential of BITC in human pancreatic cancer cells with gemcitabine resistance, namely, MIA PaCa-2/GemR cells (MIA RG100), are unclear. Materials and Methods: To elucidate the extent to which BITC induces apoptosis, we investigated the time and dose-dependent cell viability of PaCa-2/GemR cells under treatment with BITC. Results: Following BITC treatment, the PaCa-2/GemR cells exhibited DNA condensation, as indicated by transferase-mediated d-UTP nick end labeling (TUNEL) stain, with a corresponding increase in ROS production in mitochondria. Moreover, colorimetric assay analyses revealed that BITC increased caspase-9 and caspase-3 activities in PaCa-2/GemR cells. Our results indicate that BITC induces apoptotic cell death in PaCa-2/GemR cells through a mitochondrial-dependent signaling pathway.