|Table of Contents|

EGCg can induce ferroptosis in ovarian cancer cells by specifically inhibiting AADAC

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 23
Page:
4326-4333
Research Field:
Publishing date:

Info

Title:
EGCg can induce ferroptosis in ovarian cancer cells by specifically inhibiting AADAC
Author(s):
CAI Yuehong; MAI Yan; QIAN Qinjia
Department of Obstetrics and Gynecology,Sanya Central Hospital,Hainan Sanya 572000,China.
Keywords:
EGCg; AADAC; ovarian cancer; ferroptosis; GPX4
PACS:
R737.31
DOI:
10.3969/j.issn.1672-4992.2023.23.006
Abstract:
Objective:To explore the molecular mechanism of epigallocatechin gallate(EGCg) specifically inhibiting arylacetamide deacetylase(AADAC) to induce ferroptosis in ovarian cancer cells.Methods：Ovarian cancer cell lines(SK-OV-3,A2780,Hey and SW626) were cultured in vitro.CCK-8 was used to detect median inhibition concentration(IC50) of EGCg in ovarian cancer cells.The iron ion detection kit detected the content of Fe2+ions in cells.The reactive oxygen species(ROS) detection kits measured the amount of ROS in cells.The expressions of ferroptosis related proteins GPX4 and NOX1 were detected by Western blot.The effect of EGCg on AADAC activity was detected by enzyme activity test.The effect of EGCg on AADAC protein was detected by Western blot.Immunohistochemistry and Western blot were used to detect AADAC expression in ovarian cancer patients.siRNA was used to silence the expression of total AADAC in ovarian cancer cells.AADAC expression in ovarian cancer cells was knocked down by AADAC-KO.The effect of EGCg on the growth of ovarian cancer transplantation tumor was verified by subcutaneous tumorigenesis.Results:EGCg could inhibit the proliferation of ovarian cancer cells and is sensitive to SK-OV-3 and SW626 cells.EGCg increased the content of Fe2+and ROS in ovarian cancer cells,inhibited the expression of GPX4 protein and promoted the expression of NOX1 protein.EGCg could inhibit the activity and degradation of AADAC protein.AADAC was highly expressed in ovarian cancer patients.Silencing AADAC promoted ferroptosis in ovarian cancer cells.EGCg became insensitive to ovarian cancer cells after knockout of AADAC and did not promote ferroptosis.Compared with NC group,EGCg inhibited the growth of transplanted tumor in nude mice,and AADAC expression was decreased and ferroptosis was activated in transplanted tumor.Conclusion:EGCg could specifically inhibit AADAC to induce ferroptosis in ovarian cancer cells.

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海南省卫生计生行业科研计划项目（编号：18A200164）
Last Update: 2023-10-31