Natural product derivative activates autophagy in cancer cells
type: CreativeWork
description: Artemisinin, a natural product and its derivatives are potent antimalarial compounds, which have shown anticancer activity. In this study, we further characterized a novel artemisinin derivative namely EXP57EA which was previously designed and synthesized by the Chemistry Department at the University Of Cape Town. We determined the effect of EXP57EA on a panel of cancer cell lines, characterized the mode of cell death and also performed preliminary investigations of the signaling pathways that trigger the mode of cell death. Dihydroartemisinin (DHA), EXP57EA and cisplatin were screened on a selected panel of cancer cell lines: 3 esophageal cancer cell lines WHCO1, WHCO5, KYSE150; one breast cancer cell line MDA-MB-231 and one cervical cancer cell line SiHa. The 3-[4, 5-dimethylthiazol-2-yl]-2, 5- diphenyltetrazolium bromide (MTT) assay, and analysis with GraphPad prism software were used to calculate IC₅₀ values. EXP57EA displayed toxicity in the panel of cancer cell lines studied, and had lower IC₅₀ values (IC₅₀ values were ranging from 15.8 μM to 25.1 μM) than DHA and cisplatin. DHA was only active in two cells lines: WHCO1 (21.3 μM) and WHCO5 (77.3 μM), IC₅₀ values of cisplatin were ranging from 31.2 μM to 108.1 μM. EXP57EA was further investigated to understand the mode of cell death activated in the panel of cancer cell lines. The results showed that EXP57EA did not induce apoptosis in any of the cell lines studied, whereas DHA induced apoptosis, based on the PARP cleavage assay. In contrast, treatment with EXP57EA induced the appearance of vacuoles in treated cells compared to untreated cells, which was suggestive of autophagy. Autophagy was monitored by analyzing the expression level of two autophagy markers, Beclin1 and LC3-II by western blot. It was observed that EXP57EA treatment caused changes in the expression levels of both Beclin1 and LC3-II. We showed that EXP57EA induced elevated levels of autophagy, based on an increase in the flux of autophagy in t…
abstract: Artemisinin, a natural product and its derivatives are potent antimalarial compounds, which have shown anticancer activity. In this study, we further characterized a novel artemisinin derivative namely EXP57EA which was previously designed and synthesized by the Chemistry Department at the University Of Cape Town. We determined the effect of EXP57EA on a panel of cancer cell lines, characterized the mode of cell death and also performed preliminary investigations of the signaling pathways that trigger the mode of cell death. Dihydroartemisinin (DHA), EXP57EA and cisplatin were screened on a selected panel of cancer cell lines: 3 esophageal cancer cell lines WHCO1, WHCO5, KYSE150; one breast cancer cell line MDA-MB-231 and one cervical cancer cell line SiHa. The 3-[4, 5-dimethylthiazol-2-yl]-2, 5- diphenyltetrazolium bromide (MTT) assay, and analysis with GraphPad prism software were used to calculate IC₅₀ values. EXP57EA displayed toxicity in the panel of cancer cell lines studied, and had lower IC₅₀ values (IC₅₀ values were ranging from 15.8 μM to 25.1 μM) than DHA and cisplatin. DHA was only active in two cells lines: WHCO1 (21.3 μM) and WHCO5 (77.3 μM), IC₅₀ values of cisplatin were ranging from 31.2 μM to 108.1 μM. EXP57EA was further investigated to understand the mode of cell death activated in the panel of cancer cell lines. The results showed that EXP57EA did not induce apoptosis in any of the cell lines studied, whereas DHA induced apoptosis, based on the PARP cleavage assay. In contrast, treatment with EXP57EA induced the appearance of vacuoles in treated cells compared to untreated cells, which was suggestive of autophagy. Autophagy was monitored by analyzing the expression level of two autophagy markers, Beclin1 and LC3-II by western blot. It was observed that EXP57EA treatment caused changes in the expression levels of both Beclin1 and LC3-II. We showed that EXP57EA induced elevated levels of autophagy, based on an increase in the flux of autophagy in t…
author: Andong Koung Edzidzi, Ursula-Claire
language: eng
date published: 2016
date modified: 2026-07-22T22:23:34Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Division of Medical Biochemistry and Structural Biology

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property ID: Handle
value: http://hdl.handle.net/11427/24489