[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.4014/jmb.2109.09030

Chelidonium majus Induces Apoptosis of Human Ovarian Cancer Cells via ATF3-Mediated Regulation of Foxo3a by Tip60

Shen, Lei (Aerospace Center Hospital)
Lee, Soon (Division of Analytical Science, Korea Basic Science Institute)
Joo, Jong Cheon (Department of Sasang Constitutional Medicine, College of Korean Medicine, Wonkwang University)
Hong, Eunmi (Division of Analytical Science, Korea Basic Science Institute)
Cui, Zhen Yang (Rehabilitation Medicine College, Weifang Medical University)
Jo, Eunbi (Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University)
Park, Soo Jung (Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University)
Jang, Hyun-Jin (Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology)

Publication Information

Journal of Microbiology and Biotechnology / v.32, no.4, 2022 , pp. 493-503 More about this Journal

Abstract

Forkhead transcription factor 3a (Foxo3a) is believed to be a tumor suppressor as its inactivation leads to cell transformation and tumor development. However, further investigation is required regarding the involvement of the activating transcription factor 3 (ATF3)-mediated Tat-interactive protein 60 (Tip60)/Foxo3a pathway in cancer cell apoptosis. This study demonstrated that Chelidonium majus upregulated the expression of ATF3 and Tip60 and promoted Foxo3a nuclear translocation, ultimately increasing the level of Bcl-2-associated X protein (Bax) protein. ATF3 overexpression stimulated Tip60 expression, while ATF3 inhibition by siRNA repressed Tip60 expression. Furthermore, siRNA-mediated Tip60 inhibition significantly promoted Foxo3a phosphorylation, leading to blockade of Foxo3a translocation into the nucleus. Thus, we were able to deduce that ATF3 mediates the regulation of Foxo3a by Tip60. Moreover, siRNA-mediated Foxo3a inhibition suppressed the expression of Bax and subsequent apoptosis. Taken together, our data demonstrate that Chelidonium majus induces SKOV-3 cell death by increasing ATF3 levels and its downstream proteins Tip60 and Foxo3a. This suggests a potential therapeutic role of Chelidonium majus against ovarian cancer.

Keywords

Chelidonium majus; ovarian cancer; apoptosis; SKOV3; ATF3; Tip60;

Citations & Related Records

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