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

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.

• Authors: Lei Shen, Soon Lee, Jong Cheon Joo, Eunmi Hong, Zhen Yang Cui, Eunbi Jo, Soo Jung Park, Hyun-Jin Jang
• Journal: Journal of microbiology and biotechnology (J Microbiol Biotechnol) Vol. 32 Issue 4 Pg. 493-503 (Apr 28 2022) ISSN: 1738-8872 [Electronic] Korea (South)
• PMID: 35283423 (Publication Type: Journal Article)

Chemical References

• ATF3 protein, human
• Activating Transcription Factor 3
• FOXO3 protein, human
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• Gene Products, tat
• RNA, Small Interfering
• bcl-2-Associated X Protein

Topics

• Activating Transcription Factor 3 (genetics, metabolism)
• Apoptosis (genetics)
• Cell Line, Tumor
• Chelidonium (genetics, metabolism)
• Female
• Forkhead Box Protein O3 (metabolism)
• Forkhead Transcription Factors (genetics, metabolism)
• Gene Products, tat
• Humans
• Ovarian Neoplasms
• RNA, Small Interfering (genetics)
• bcl-2-Associated X Protein