AI Article Synopsis
- This study explores the effectiveness of new compounds, adamantyl-N-acetylcystein and adamantyl isothiocyanate, in treating gynecological cancers, showing they can kill cancer cells in lab tests.
- The compounds were found to halt the cancer cell cycle specifically in SKOV-3 ovarian cancer cells and induced apoptosis, evidenced by DNA fragmentation.
- Adamantyl-N-acetylcystein’s cytotoxic effects rely on increased reactive oxygen species, and future research may enhance its efficacy using signaling inhibitors or antioxidant treatments in real tumor models.
Article Abstract
This study determined the in vitro potential of novel compounds adamantyl-N-acetylcystein and adamantyl isothiocyanate to treat gynecological cancers. Adamantyl-N-acetylcystein is postulated to be an in vivo metabolite of adamantyl isothiocyanate as dietary isothiocyanates are converted to N-acetylcysteine-conjugates. A viability assay suggested that adamantyl isothiocyanate and adamantyl-N-acetylcystein are cytotoxic to cancer cells including gynecological cell lines. A NCI60 cancer cell assay revealed that growth-inhibition and cytotoxicity of adamantyl-N-acetylcystein were cell line, but not tissue type-specific. Cell cycle studies revealed that adamantyl-N-acetylcystein and adamantyl isothiocyanate arrest SKOV-3 ovarian cancer cells in G2/M phase. By TUNEL, immunoblotting, and viability studies employing caspase and p38 mitogen-activated protein kinase inhibitors, we proved that reduction in SKOV-3 viability is a consequence of DNA fragmentation and apoptosis. Cytotoxic action of adamantyl-N-acetylcystein in SKOV-3 and endometrial cancer (ECC-1, RL95-2, AN3CA, and KLE) cells required excess generation of reactive oxygen species which could be blocked by antioxidant co-treatment. Adamantyl-N-acetylcystein treatment led to modified expression or activation of apoptotic and oncogenic proteins such as JNK/SAPK, AKT, XIAP, and EGF-R for SKOV-3 and JNK/SAPK and ERK1/2 for ECC-1 cells. We suggest the further development of adamantyl-N-acetylcystein by sensitizing cells to the drug using signaling inhibitors or redox-modulating agents and by evaluating the drug efficacy in ovarian and endometrial in-vivo tumor models.
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| http://dx.doi.org/10.1111/j.1747-0285.2011.01251.x | DOI Listing |
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Article Synopsis
- This study explores the effectiveness of new compounds, adamantyl-N-acetylcystein and adamantyl isothiocyanate, in treating gynecological cancers, showing they can kill cancer cells in lab tests.
- The compounds were found to halt the cancer cell cycle specifically in SKOV-3 ovarian cancer cells and induced apoptosis, evidenced by DNA fragmentation.
- Adamantyl-N-acetylcystein’s cytotoxic effects rely on increased reactive oxygen species, and future research may enhance its efficacy using signaling inhibitors or antioxidant treatments in real tumor models.
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Bioorg Med Chem
May 2004
University of Agricultural Sciences and Veterinary Medicine, Faculty of Biotechnologies, Department of Chemistry, B-dul Marasti nr. 59, 71331 Bucharest, Romania.
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