Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src‑mediated phosphorylation of EGF receptor tyrosine kinase.

摘要: Thymoquinone (TQ), a compound isolated from black seed oil (Nigella sativa), has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying effects of TQ remain poorly understood. In present study, we found that significantly reduced viability human colon cancer HCT116 cells in concentration- time-dependent manner. Treatment with induced apoptosis, which was associated upregulation Bax inhibition Bcl-2 Bcl-xl expression. also activated caspase-9,-7, -3, cleavage poly-(ADP-ribose) polymerase (PARP). Pretreatment pan-caspase inhibitor, z-VAD-fmk, abrogated TQ-induced apoptosis by blocking caspase-3 PARP. diminished constitutive phosphorylation, nuclear localization reporter gene activity signal transducer activator transcription-3 (STAT3). attenuated expression STAT3 target products, such as survivin, c-Myc, cyclin-D1, -D2, enhanced cell cycle inhibitory proteins p27 p21. phosphorylation upstream kinases, Janus-activated kinase-2 (JAK2), Src kinase epidermal growth factor receptor (EGFR) tyrosine kinase. Pharmacological JAK2 blunted EGFR STAT3, while treatment an inhibitor gefitinib inhibited without affecting cells. Collectively, our study revealed signaling via JAK2- Src-mediated