Abstract
Combretum species are distributed widely in Southern Africa and are known for their medicinal properties. The species have potential as sources of anticancer agents. Combrestanin-A4 isolated from Combretum caffrum is one of the pure compounds now under clinical trials. The aim of this study was to fractionate and isolate plant phytoconstituents of C. platypetalum and determine their antiproliferative effects on a human leukemic cancer cell line, Jurkat-T cells. Dried powdered leaf plant samples were extracted serially with hexane, DCM, acetone, ethyl acetate, ethanol, methanol, and water. The total combined extracts were run on a silica gel column using a mobile phase of increasing polarity. β-Sitosterol was isolated from pool 94–98 of the fractions and identified by 1H-NMR and 13C-NMR and its molecular formula confirmed by mass spectrometry. The effects of β-sitosterol on proliferation of cells, effect of combining β-sitosterol and glutathione, effect of combining β-sitosterol and camptothecin and effect of β-sitosterol on glutathione S-transferase activity were determined. β-sitosterol showed dose-dependent antiproliferative effects against Jurkat-T cells and these effects were shown to be irreversible. Reduced glutathione protected the cells from the effects of β-sitosterol. Enhance antiproliferative effects were observed when β-sitosterol was combined with camptothecin. β-sitosterol was also shown to inhibit the activity of glutathione S-transferases in the cancer cell line. The results of the study suggested that β-sitosterol has antiproliferative effects in the Jurkat-T cells. Further work needs to be done on normal cells to determine if β-sitosterol affects cancer cells only.
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Abbreviations
- GST:
-
Glutathione transferases
- GSH:
-
Reduced glutathione
- PBS:
-
Phosphate buffered saline
- PNS:
-
Penicillin, streptomycin and neomycin solution
- FBS:
-
Foetal bovine serum
- CDNB -1:
-
Chloro-dinitro benzene
- TOF:
-
Time of flight
- DMSO:
-
Dimethylsulfoxide
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Acknowledgements
The authors acknowledge the assistance of the Department of Chemistry, and Network for Analytical and Bioassay Services in Africa (NABSA) University of Botswana, for column chromatographic analyses of plant samples for the corresponding author in July 2015.
Funding
Support from the Swedish International Development Agency (SIDA) through the International Science Programmes (ISP-IPICS-ZIM01, Uppsala University, Sweden) is acknowledged. The authors also acknowledge support from the Alliance of Global Health and Science (University of California, Berkeley, USA).
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The study was conducted according to the protocol approved by the Department of Biochemistry HBC 470 Board, Paper R122884E of 2016, University of Zimbabwe.
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Auxillia Machingauta has no conflict of interest. Marc Y. Stevens has no conflict of interest. Chi Godloves Fru has no conflict of interest. Simbarashe Sithole has no conflict of interest. Samuel Yeboah has no conflict of interest. Stanley Mukanganyama has no conflict of interest.
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Machingauta, A., Stevens, M.Y., Fru, C.G. et al. Evaluation of the antiproliferative effect of β-sitosterol isolated from Combretum platypetalum Welw. ex M.A. Lawson (Combretaceae) on Jurkat-T cells and protection by glutathione. ADV TRADIT MED (ADTM) 22, 865–873 (2022). https://doi.org/10.1007/s13596-022-00650-6
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DOI: https://doi.org/10.1007/s13596-022-00650-6