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DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells
Xuekun Nie1, Huajiao Chen2, Peiguang Niu2
1Department of Pharmacy, Ningde Municipal Hospital, Affiliated Hospital of Fujian Medical University, Ningde, Fujian, China.
Abstract:
Autophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death-associated protein 1) is a proline-rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.
Insights
Cardamonin induces autophagy and inhibits ovarian cancer cell proliferation by targeting mammalian target of rapamycin (mTOR). Death-associated protein 1 (DAP1) negatively regulates this process, suggesting DAP1 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Autophagy plays a critical role in human tumor development, including ovarian cancer.
- Mammalian target of rapamycin (mTOR) is a key regulator of autophagy.
- Cardamonin, a plant-derived flavonoid, induces autophagy and inhibits cancer cell proliferation, but its mechanism is not fully understood.
Purpose of the Study:
- To investigate the role of death-associated protein 1 (DAP1) in cardamonin-induced autophagy and proliferation inhibition in tumor cells.
- To explore the potential of DAP1 as a therapeutic target for ovarian cancer.
Main Methods:
- Bioinformatic analysis of DAP1 expression in ovarian cancer patients.
- In vitro studies using SKOV3 ovarian cancer cells.
- Manipulation of DAP1 expression using small interfering RNA (siRNA).
- Assessment of autophagy induction, mTOR signaling, and cell proliferation.
Main Results:
- DAP1 expression correlates with patient survival in ovarian cancer.
- Cardamonin-induced autophagy is linked to mTOR inhibition.
- DAP1 silencing reduced cell proliferation and enhanced cardamonin's antiproliferative effects.
- DAP1 silencing elevated autophagy levels and increased autophagy flux in response to cardamonin.
Conclusions:
- DAP1 negatively regulates cardamonin-induced autophagy.
- DAP1 plays a role in ovarian cancer cell proliferation and response to cardamonin.
- DAP1 represents a potential therapeutic target for ovarian cancer treatment.
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