GB12

GB12 is a 3,5-dibenzoyl-1,4-dihydropyridine that demonstrates tumor-specific cytotoxic activity. It exhibits significantly higher cytotoxicity against various human tumor cell lines, including squamous cell carcinoma (HSC-2, HSC-3), submandibular gland carcinoma (HSG), and promyelocytic leukemia (HL-60), compared to human normal cells. While it weakly induces apoptosis-associated properties such as internucleosomal DNA fragmentation and activation of caspases -3, -8, and -9, it also transiently increases the expression of both anti-apoptotic protein Bcl-2 and proapoptotic proteins Bax and Bad in HL-60 cells. The cytotoxic mechanism is suggested to involve non-apoptotic cell death, as it does not appear to be mediated by radical production or scavenging of superoxide or nitric oxide.