Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines

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dc.contributor.author Nel, Marcel
dc.contributor.author Joubert, Anna Margaretha
dc.contributor.author Dohle, Wolfgang
dc.contributor.author Potter, Barry V.L.
dc.contributor.author Theron, A.E. (Anne Elisabeth)
dc.date.accessioned 2018-09-21T06:41:48Z
dc.date.available 2018-09-21T06:41:48Z
dc.date.issued 2018
dc.description The abstract of this paper was presented at the 24 Biennial Congress of the European Association for Cancer Research, July 9–12, 2016, Manchester, UK, and was published in the European Journal of Cancer. en_ZA
dc.description.abstract BACKGROUND : A and B rings of the steroidal microtubule disruptor, 2-methoxyestradiol, and its analogs can be mimicked with a tetrahydroisoquinoline (THIQ) core. THIQs are cytotoxic agents with potential anticancer activities. The aim of this in vitro study was to investigate the modes of cell death induced by four nonsteroidal THIQ-based analogs, such as STX 2895, STX 3329, STX 3451 and STX 3450, on MDA-MB-231 metastatic breast and A549 epithelial lung carcinoma cells. MATERIALS AND METHODS : Cytotoxicity studies determined the half-maximal growth inhibitory concentration of the analogs to be at nanomolar concentrations without the induction of necrosis. Light and fluorescent microscopy determined that compounds caused microtubule depolymerization and displayed morphological hallmarks of apoptosis. RESULTS : Flow cytometric analyses confirmed apoptosis induction as well as an increased G2/M phase on cell cycle analysis. Furthermore, intrinsic pathway signaling was implicated due to increased cytochrome c release and a decrease in mitochondrial transmembrane potential. Potential involvement of autophagy was observed due to increased acidic vacuole formation and increased aggresome activation factor. CONCLUSION : Thus, it can be concluded that these four THIQ-based analogs exert anti- proliferative and antimitotic effects, induce apoptosis and involve autophagic processes. Further investigation into the efficacy of these potential anticancer drugs will be conducted in vitro and in vivo. en_ZA
dc.description.department Physiology en_ZA
dc.description.librarian am2018 en_ZA
dc.description.sponsorship Grants from the Medical Research Council of South Africa, the Cancer Association of South Africa, National Research Foundation and the Struwig-Germeshuysen Cancer Research Trust of South Africa. BVLP is a Wellcome Trust Senior Investigator (grant 101010). en_ZA
dc.description.uri http://www.dovepress.com/drug-design-development-and-therapy-journal en_ZA
dc.identifier.citation Nel, M., Joubert, A.M., Dohle, W. et al. 2018, 'Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines', Drug Design, Development and Therapy, vol. 12, pp. 1881-1904. en_ZA
dc.identifier.issn 1177-8881 (online)
dc.identifier.other 10.2147/DDDT.S152718
dc.identifier.uri http://hdl.handle.net/2263/66618
dc.language.iso en en_ZA
dc.publisher Dove Medical Press en_ZA
dc.rights © 2018 Nel et al. This work is published and licensed by Dove Medical Press Limited. Creative Commons Attribution – Non Commercial (unported, v3.0) License. en_ZA
dc.subject Cancer en_ZA
dc.subject Apoptosis en_ZA
dc.subject Autophagy en_ZA
dc.subject Antimitotic en_ZA
dc.subject Nonsteroidal en_ZA
dc.subject Induction en_ZA
dc.subject Degradation en_ZA
dc.subject Agents en_ZA
dc.subject 2-Methoxyestradiol (2ME2) en_ZA
dc.subject In vitro en_ZA
dc.subject Cycle arrest en_ZA
dc.subject In vivo activity en_ZA
dc.subject Chimeric microtubule disruptor en_ZA
dc.title Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines en_ZA
dc.type Article en_ZA


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