Objective: Doxorubicin is a potent anti-cancer agent with efficacy against a broad range of tumors, including endometrial cancer. Doxorubicin produces reactive oxygen species (ROS) resulting in cytotoxicity. Tetrathiomolybdate (TM), a copper-chelating agent, is known to target a cellular antioxidant enzyme copper/zinc-superoxide dismutase. This study tests the hypothesis that TM can modulate antioxidants in tumor cells and render doxorubicin resistant tumor cells sensitive to doxorubicin.
Methods: The anti-cancer activities of doxorubicin and TM, as single agents and in combination, were assessed. Flow cytometric and immunoblot analysis were conducted to investigate the induction of apoptosis and changes in apoptotic signaling pathways.
Results: Doxorubicin-induced growth inhibition was observed in each endometrial cancer cell line (ECC-1, AN3CA, and KLE) tested with cell specificity. ECC-1 and KLE cells were found to have increased resistance to doxorubicin than AN3CA cells. Moreover, doxorubicin mediated apoptosis was greater in the AN3CA cell line than ECC-1 and KLE. The combination of doxorubicin with a sub-cytotoxic level of TM was significantly more effective at inducing apoptosis in doxorubicin resistant cell lines.
Conclusion: Our results highlight the therapeutic potential of TM to sensitize tumor cells to doxorubicin for endometrial cancer treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ygyno.2011.03.035 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Elevated LINC00115 expression correlates with aggressive endometrial cancer phenotypes via JAK/STAT pathway modulation.
Hum Mol Genet
January 2025
Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of CM, No. 19, Renmin Road, Jinshui District, Zhengzhou City, Henan Province, China.
This study systematically explores the oncogenic role of the long non-coding RNA (lncRNA) LINC00115 in endometrial cancer (EC) and reveals its unique mechanism in promoting proliferation, invasion, and metastasis via the JAK/STAT signaling pathway. LINC00115 is significantly upregulated in EC tissues and closely associated with advanced TNM staging and lymph node metastasis. Functional assays showed that knockdown of LINC00115 suppressed EC cell proliferation, invasion, and metastasis, while overexpression enhanced these malignant behaviors.
View Article and Find Full Text PDFUnlabelled: In most cancers, including endometrial cancer, tumor suppressor genes harboring inactivating mutations have been systematically cataloged. However, locus-specific epigenetic alterations contributing to cancer initiation and progression remain only partly described, creating knowledge gaps about functionally significant tumor suppressors and underlying mechanisms associated with their inactivation. Here, we show that PAX2 is an endometrial tumor suppressor recurrently inactivated by a distinct epigenetic reprogramming event not associated with promoter hypermethylation.
View Article and Find Full Text PDFA case of large uterine cystic adenomyosis outside the uterus after laparoscopic myomectomy: a case report and literature review.
BMC Womens Health
January 2025
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, China.
Background: Uterine cystic adenomyosis is a rare form of focal adenomyosis that is primarily located within the myometrium. In this case report, we present a unique case of adult uterine cystic adenomyosis found outside the uterus following laparoscopic myomectomy.
Case Presentation: The patient was a 36-year-old Chinese woman who had previously undergone laparoscopic surgery at our hospital to remove a 4 cm diameter diameter uterine fibroid six years prior.
A risk prediction model for endometrial hyperplasia/endometrial carcinoma in premenopausal women.
Sci Rep
January 2025
Department of Gynecology, Chongqing Ninth People's Hospital, 69, Jialing Village, Beibei District, Chongqing, 400700, China.
This study investigated the risk factors for endometrial hyperplasia (EH) and endometrial carcinoma (EC) in premenopausal women. The goal was to establish a nomogram model to predict the risk of EH/EC and quantitative standards in clinical practice, which improved the clinical prognosis of EH/EC patients. Data were collected from premenopausal women with suspected EH/EC who underwent hysteroscopic endometrial biopsy.
View Article and Find Full Text PDFBioinformatics approaches to multi-omics analysis of the potential of CDKN2A as a biomarker and therapeutic target for uterine corpus endometrial carcinoma.
Sci Rep
January 2025
Biochemistry and Molecular Biology, College of Basic Medical Science, Chongqing Medical University, Chongqing, 400000, China.
Uterine corpus endometrial carcinoma (UCEC) is a significant cause of cancer-related mortality among women worldwide. Prior research has demonstrated an association between cyclin-dependent kinase inhibitor 2 A (CDKN2A) and various tumors. As a member of the INK4 family, CDKN2A is involved in cell cycle regulation by controlling CDKs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!