Anticancer Activities Of Solvent Fractions And Of Sesquiterpene Lactones Isolated From Selected Ethiopian Traditional Medicinal Plants

The incidence and mortality of breast cancer in women is increasing worldwide. Breastrncancer has high intertumoral and intratumoral heterogeneity. Cancer stem cells (CSCs)rnare one of the many subpopulations of cancer cells and are involved in tumor initiation,rnprogression, evolution and metastasis, and are believed to be responsible forrnchemotherapeutic resistance. The present study investigated in vitro anticancerrnactivities of extracts from seven medicinal plants traditionally used to treat breastrncancer in Ethiopia. Chemical compounds were also isolated from the most potentrnbioactive fractions. The study determined cytotoxicity of the crude methanol extractsrn(80 %, v/v) and that of solvent fractions (1:1, v/v) of the most cytotoxic ones.rnFurthermore, the anti-CSCs potency of the bioactive solvent fractions and the isolatedrncompounds were also investigated. Vacuum liquid chromatography, preparative thinrnlayer chromatography, column chromatography and high-resolution electrosprayrnionization mass spectrometry (HR-ESI-MS) were employed for the phytochemicalrncharacterization. Cytotoxicity of the phytochemicals against the human breast cancerrncell lines, JIMT-1, HCC1937 and MCF-7 and the normal-like breast epithelial cell line,rnMCF-10A, was determined by a spectrophotometric MTT assay. To investigaternspecific activity against CSCs, flow cytometric determination of the aldehyderndehydrogenase (ALDH) positivity and determination of CD44+/CD24- CSCrnsubpopulations as well as the colony forming efficiency (CFE) in a serum-free soft agarrnivrnwere performed. The effects of phytochemical treatment on tumor necrosis factor-αrn(TNF-ɑ)-induced translocation of the nuclear factor-kappa B (NF-κB) to the nucleusrnand on cell migration in a wound healing assay were also investigated. The halfrnmaximal inhibitory concentrations (IC50) were determined for the crude methanolrnextract of Sideroxylon oxyacanthum (0.09 μg/mL, MCF-7), Clematis simensis (0.17rnμg/mL, HCC1937) and Dovyalis abyssinica (0.21 μg/mL, MCF-7). Ethyl acetaternsolvent fraction of V. leopoldi was the most cytotoxic against JIMT-1 cells (IC50 = 0.87rnμg/mL). The bioactive solvent fractions of V. leopoldi, S. oxyacanthum and C. simensisrnshowed dose dependent reduction in the ALDH+ subpopulation of JIMT-1 cells. Thernchloroform fraction of C. simensis (80 μg/mL) completely blocked CFE in JIMT-1rncells. The bioactive solvent fractions of V. leopoldi, S. oxyacanthum and C. simensisrnsignificantly reduced cell migration (P

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