Nagoya University demonstrates antitumor effects of eggplant-derived component: Successful inhibition of cervical cancer cell proliferation

A research group led by Graduate Student Kazumasa Mogi, Assistant Professor Masato Yoshihara, and Professor Hiroaki Kajiyama of the Department of Obstetrics and Gynecology at Nagoya University Graduate School of Medicine, in collaboration with Bell Research Center, discovered that 9-oxo-octadecadienoic acids (9-oxo-ODAs), natural compounds in the eggplant calyx (the outermost leafy structure at the base of the vegetable), have antitumor effects on cervical cancer cells. In the experiments using mouse models, the administration of 9-oxo-ODAs inhibited the proliferation and metastasis of cervical cancer cells implanted in mice. The findings are expected to lead to the development of therapeutic drugs against cervical cancer and cervical dysplasia and were published on November 6 in the international academic journal Scientific Reports.

Human papillomavirus (HPV) is a virus that causes cervical cancer, a major cause of cancer-related deaths among women worldwide. In Japan, 2887 women died from cervical cancer in 2020.

When the epithelium of the cervical mucosa is infected with HPV, cervical dysplasia can result as a precancerous lesion and progresses to invasive cervical cancer within a few years to decades. Although the E6 and E7 protein derived from HPV are reported to be associated with the progression of cervical cancer, no molecularly targeted drug or therapeutic approach has been established.

In previous research, the research group had found that an ethanol extract from the eggplant calyx suppresses ovarian cancer cells and condyloma acuminatum (genital warts), and they identified 9-oxo-ODAs as the active components in the extract. Eggplant calyxes have been used in Japan as a folk remedy for common warts, another HPV-related disease.

In the current study, the research group verified the antitumor effects of 9-oxo-ODAs on human cervical cancer. Through treating human cervical cancer cells (HeLa and SiHa) with 9-oxo-ODAs, the effects on cell proliferation and apoptosis induction were examined. As a result, the proliferation of the human cervical cancer cells was inhibited in a concentration-dependent manner, and the number of apoptotic cells increased.

Comprehensive analyses of RNA and protein expression in the cervical cancer cell lines treated with 9-oxo-ODAs revealed that the cell cycle and apoptosis-related p53 pathways were altered, and the expression of cyclin-dependent kinase 1 protein was downregulated. In the cervical cancer cell lines treated with 9-oxo-ODAs, the expression levels of HPV-derived RNAs and proteins were reduced. In mouse models implanted with cervical cancer cells, the administration of 9-oxo-ODAs inhibited the proliferation and metastasis of the cells. These results indicate that 9-oxo-ODAs exhibit antitumor effects by inducing cell cycle arrest and the apoptosis of HPV-positive human cervical cancer cells.

Mogi commented on the result, "9-oxo-ODAs are natural compounds from eggplants. Because of their low toxicity to the human body, they can be expected to be developed into safe and effective therapeutic drugs. In the future, we would like to further explore how 9-oxo-ODAs exert antitumor effects on cervical cancer cells to achieve their clinical application."