9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins

Kazumasa Mogi, Yoshihiro Koya, Masato Yoshihara, Mai Sugiyama, Rika Miki, Emiri Miyamoto, Hiroki Fujimoto, Kazuhisa Kitami, Shohei Iyoshi, Sho Tano, Kaname Uno, Satoshi Tamauchi, Akira Yokoi, Yusuke Shimizu, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kaoru Niimi, Yoshihiko Yamakita, Hiroyuki Tomita, Kiyosumi ShibataAkihiro Nawa, Yutaka Tomoda, Hiroaki Kajiyama

Research output: Contribution to journalArticlepeer-review

Abstract

Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25–50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.

Original languageEnglish
Article number19208
JournalScientific reports
Volume13
Issue number1
DOIs
Publication statusPublished - 12-2023

All Science Journal Classification (ASJC) codes

  • General

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