Insights into Cytostatic and Cytotoxic Properties of the Natural Product Mensacarcin

Graduate Thesis Or Dissertation

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Citeable URL: https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/qj72pd90x

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Attribute Name	Values
Creator	Kaweesa, Elizabeth Namagoba
Abstract	Mensacarcin is a stereogenic complex polyketide with potent anti-tumor activity produced by a soil-dwelling Streptomyces bottropensis. The US National Cancer Institute (NCI) 60 human tumor cell line anticancer drug screen (NCI-60) reveals mensacarcin’s cytostatic properties in almost all tested cell lines and distinct cytotoxic properties specifically in eight melanoma cell lines with an average IC50 value of 0.5-1 μM. We show that mensacarcin activates caspase-3/7-dependent apoptotic pathways and induces apoptosis in melanoma cells and not colon cancer carcinoma cells. Mensacarcin co-localizes in mitochondria and impairs mitochondrial function by either inhibiting mitochondria respiration directly or by causing general mitochondrial dysfunction. Combination of mensacarcin and the standard chemotherapeutic regime for BRAF-mutant melanoma, vemurafenib/zelboraf®, increases efficacy and cytotoxicity synergistically.
License	All rights reserved
Resource Type	Masters Thesis
Date Issued	2018-10-02
Degree Level	Master's
Degree Name	Master of Science (M.S.)
Degree Field	Chemistry
Degree Grantor	Oregon State University
Commencement Year	2019
Advisor	Loesgen, Sandra
Committee Member	Blakemore, Paul Mahmud, Taifo Kolluri, Siva Ishmael, Jane
Academic Affiliation	Chemistry
Rights Statement	In Copyright
Publisher	Oregon State University
Peer Reviewed	No
Language	English [eng]
Embargo reason	Ongoing Research
Embargo date range	2019-02-21 to 2020-03-21

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