Inhibition of JAK2/STAT3 and activation of caspase ‑9/3 are involved in KYS05090S‑induced apoptosis in ovarian cancer cells.

Inhibition of JAK2/STAT3 and activation of caspase‑9/3 are involved in KYS05090S‑induced apoptosis in ovarian cancer cells. Int J Oncol. 2019 May 03;: Authors: Kim BI, Kim JH, Sim DY, Nam M, Jung JH, Shim B, Lee J, Kim SH Abstract To overcome the poor prognosis of patients with ovarian cancer, attempting to target ovarian cancer with effective antitumor compounds has been conducted for numerous years. Although the 3,4‑dihydroquinazoline derivative KYS05090S was known to exert antitumor effects in A549 and ovarian cancer cells by inhibition of T‑type Ca2+ channels, the complete underlying antitumor mechanism of this compound remains unclear. Thus, in the present study, the potential apoptotic mechanism of KYS05090S was elucidated in SKOV3 and OVCAR3 ovarian cancer cells. KYS05090S exerted significant cytotoxicity in SKOV3 and OVCAR3 ovarian cancer cells, and also increased the number of apoptotic bodies, and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and the sub‑G1 population as a feature of apoptosis. Consistently, KYS05090S induced cleavage of poly(ADP‑ribose) polymerase and caspase‑9/3 in ovarian cancer cells. Notably, KYS05090S attenuated the expression of anti‑apoptotic proteins, including cyclin D1 and B‑cell lymphoma‑2 (Bcl‑2), and reduced the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in ovaria...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research