Anti-Tumor Studies Of A Selection Of Sudanese Indigenous Herbs Via The Angiogenesis Pathway
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Date
2015-10
Authors
Hassan, Loiy Elsir Ahmed
Journal Title
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Publisher
Universiti Sains Malaysia
Abstract
The aim of the present study is to investigate six Sudanese medicinal plants for anticancer activity. Different parts of these plants were selected to prepare 32 extracts using sequential extraction method with 4 solvents of different polarity. Amongst the six Sudanese medicinal plants tested, N. glauca, T. apollinea, C. hartmannianum and T. nilotica were found to be most biologically active with significant antiangiogenic and antineoplastic effects. Their biological activities observed were found to be attributed to their high antioxidant activity due to the presence of high amount of phenolic and flavonoid substances.
The results of present study indicate that the ethanol extract of T. apollinea possess the highest antiangiogenic effect when compared to the other plant species and it significantly inhibited the growth of colon cancer in vivo. The extract was found to halt angiogenesis by inhibiting cell migration, endothelial tube formation and most importantly the inhibition of VEGF expression. The key compounds that contribute to this activity are three prenylated flavonoids namely (-)-pseudosemiglabrin (SSG), (-)-semiglabrin (SG) and Isoglabratephrin (IGP). SSG was found to be the most abundant and the most active as antiangiogenic when compared to SG and IPG. SSG inhibits the COX enzymes with strong preference towards the COX-2 enzymes. It also suppresses production of cytokines IL-1 and TNF-α but it not significant effect towards nitric oxide (NO) expression, IL-1 and TNF-α are key inflammatory mediators that plays crucial role in carcinogenesis. SSG showed potent in vivo antitumor activity towards ectopic and orthotopic xenograft model of colon cancer with the latter indicating the inhibition MMP 9 expression. Amongst the three compounds only SSG showed cytotoxic activity particularly towards colon cancer (HCT116), breast cancer (MCF7), prostate cancer (PC3) and leukemia (HL-60) cell lines. The compound targets the mitochondrial function by disrupting the integrity of its cellular matrix. The isolated compounds were used to standardize the ethanol extract of T. apollinea by HPLC method. The study indicated that the antiangiogenic and antitumor activity of T. apollinea ethanol extract is contributed mainly by SSG. All in all, the data shows that extract of T. apollinea and its active compound SSG, as potential antitumor agents that modulate their activity via the antiproliferative and angiogenesis cascade.
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Keywords
Anticancer activity