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

Kim,Bo‑Im; Kim,Ju‑Ha; Sim,Deok Yong; Nam,Minho; Jung,Ji Hoon; Shim,Bumsang; Lee,Jaeyeol; Kim,Sung‑Hoon

doi:10.3892/ijo.2019.4795

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

Authors:
- Bo‑Im Kim
- Ju‑Ha Kim
- Deok Yong Sim
- Minho Nam
- Ji Hoon Jung
- Bumsang Shim
- Jaeyeol Lee
- Sung‑Hoon Kim
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Affiliations: Department of Pathology, College of Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea, Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea
Published online on: May 3, 2019 https://doi.org/10.3892/ijo.2019.4795
Pages: 203-210

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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 ovarian cancer cells. Additionally, KYS05090S blocked the nuclear translocation of STAT3 and suppressed the signaling of JAK2/STAT3 in interleukin‑6‑treated SKOV3 cells, as a STAT3 activator. Overall, these observations indicated that inhibition of JAK2/STAT3 signaling and activation of caspase‑9/3 are critically involved in the effects of KYS05090S on apoptosis in ovarian cancer types, and the compound may be beneficial as a potent antitumor agent.

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