Evaluation of the cancer specificity of intracellular events caused by 2-methoxyestradiol-bis-sulphamate and aqueous Sutherlandia frutescens extracts

This study investigated effects elicited by 2-methoxyestradiol-bis-sulphamate and aqueous Sutherlandia frutescens extracts in the MCF-7 breast adenocarcinoma and the non-tumorigenic MCF-12A cell lines demonstrating encouraging degrees of anti-cancer activity warranting further research.This paper was initially delivered at the Annual Congress of the Biological Sciences Division of the South African Academy for Science and Art, ARC-Plant Protection Research Institute, Roodeplaat, Pretoria, South Africa on 01 October 2010.http://www.satnt.ac.zaam2014ay201

Differential signaling involved in Sutherlandia frutescens-induced cell death in MCF-7 and MCF-12A cells

Ethnopharmacological relevance: The scientific study of natural products traditionally used in anticancer preparations has yielded several therapeutically relevant compounds. One of these traditional preparations with potentially beneficial properties is aqueous extracts of Sutherlandia frutescens, a shrub indigenous to the Western Cape region of South Africa. Aims of the study: To evaluate in vitro efficacy of these preparations on the MCF-7 breast adenocarcinoma and MCF-12A non-tumorigenic cell lines in terms of cell proliferation, cell morphology and possible induction of cell death. Materials and Methods: Crystal violet staining was used to evaluate cell proliferation, lightand fluorescence microscopy were used to investigate both intracellular and extracellular morphological features of apoptosis and autophagy (e.g. membrane blebbing, condensed chromatin and intracellular lysosomes), while flow cytometry quantified cell cycle changes and induction of apoptosis through analysis of the flip-flop translocation of phosphatidylserine.The Medical Research Council of South Africa (AK076; AL343). The Cancer Association of South Africa (AK246).The National Research Foundation of South Africa (AL239) and the Struwig-Germeshuysen Cancer Research Trust of South Africa (AN074).http://www.elsevier.com/locate/jethpharmhb201

In vitro effects of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology and cell cycle dynamics in the MCF-7 breast adenocarcinoma cell line

In the search for new and improved anticancer therapies, researchers have identified several potentially useful compounds. One of these agents is 2-methoxyestradiol-bis-sulphamate (2ME-BM), a sulphamoylated derivative of 2-methoxyestradiol. The objective of this study was to evaluate 2ME-BM’s in vitro efficacy as antiproliferative agent in the MCF-7 breast adenocarcinoma cell line. Light- and fluorescent microscopy showed decreased cell density, increased apoptotic characteristics and significant ultrastructural aberrations indicative of autophagic cell death after 24 hours of exposure at a concentration of 0.4μM. In addition, mitotic indices revealed that 2ME-BM induces a G2M block. The latter was confirmed by flow cytometric analyses where increased sub-G1 and G2/M fractions, as well as an increase in cyclin B1 levels were observed. Further in vitro research into the mechanism of this potentially useful anticancer compound is thus warranted.This research was supported by grants from the Medical Research Council of South Africa (AK076; AL343), the Cancer Association of South Africa (AK246), the National Research Foundation of South Africa (AL239) and the Struwig-Germeshuysen Cancer Research Trust of South Africa (AN074)

In vitro of 2-methoxyestradiol on morphology, cell cycle progression, cell death and gene expressions changes in the tumorigenic MCF-7 breast epithelial cell line

In the present study, the antiproliferative mechanism of action of 1 M 2-methoxyestradiol (2ME) was investigated in the MCF-7 cell line. Measurement of intracellular cyclin B and cytochrome c protein levels, reactive oxygen species formation, cell cycle progression and apoptosis induction were conducted by means of flow cytometry. Morphological changes were evaluated using transmission electron microscopy and fluorescent microscopy by employing Hoechst 33342 and acridine orange. Gene expression changes were conducted by means of microarrays. 2ME-treated cells demonstrated an increase in cyclin B protein levels, hydrogen peroxide formation, intracellular levels of cytochrome c, as well as an increase in early and late stages of apoptosis. In addition, morphological data revealed the presence of autophagic processes. Fluorescent microscopy showed an increase in acridine orange staining and electron microscopy revealed an increase in vacuolar formation in 2ME-treated cells. The gene expression of several genes associated with mRNA translation, autophagy-related processes and genes involved in microtubule dynamics were affected. The study contributes to the mechanistic understanding of 2ME’s growth inhibition in MCF-7 cells and highlights the possibility of both apoptotic and autophagic processes being activated in response to 2ME treatment in this cell line.Medical Research Council of South Africa (AG374, AK076), the Cancer Association of South Africa (AK246) and the Struwig-Germeshuysen Cancer Research Trust of South Africa (AJ038).http://www.elsevier.com/wps/find/journaldescription.cws_home/333/description#descriptio