Abstract

Plants are a source of over a quarter of the prescription drugs currently in use worldwide. Zimbabwe has a rich plant biodiversity with only a limited number reported for the treatment of cancer. The leaf extracts of Dolichos kilimandscharicus were selected for the screening of their antiproliferative efficacy and cytotoxicity effects. This plant has increasingly been used by local folk as a treatment for cancer or cancer-related symptoms though its bioactivity has not been scientifically determined. This investigation also sought to identify constituent compounds in the crude extract preparations responsible for their antiproliferative efficacy. The antiproliferative effects of six-leaf extracts on Jurkat-T in vitro were investigated using the Trypan blue exclusion assay. The extracts were tested with increasing concentration, using chlorambucil as a standard anticancer drug. Cytotoxicity of extracts was determined against RAW 264.7 cells using a colorimetric tetrazolium-based assay. In additionthe ability of the extracts to induce apoptosis was determined for the most potent leaf extracts. The order of potency of the leaf extracts of D. kilimandscharicus against Jurkat-T cell line was found to be MeOH < Ethyl Acetate < DCM: MeOH < EtOH with IC50s of 33.56, 30.44, 22.93, and 21.59 μg/mL, respectively. Furthermore, the most potent extracts exhibited very low cytotoxicity against all the tested cells. D. kilimandscharicus leaf extracts induced apoptosis in the Jurkat-T cells as was shown by DNA fragmentation. UPLC-MS analysis of crude extracts led to the identification of 23 compounds from the ethanol extract and these may be responsible for the observed antiproliferative effects. Rutin, quercetin, luteolin, apigenin, hispidulin, kaempferol derivatives, as well as caffeoylquinic acid are some of the compounds identified in the extracts. The results of this study showed that the ethanol and ethyl acetate leaf extracts of D. kilimandscharicus have antiproliferative activity against Jurkat-T cells and may act by inducing apoptosis.. The current findings offer supporting evidence for the use of these plant species in the treatment of cancer in ethnomedicinal practices.

Highlights

  • The World Health Organization estimated cancer deaths to be over 9.6 million in 2018, with most of these deaths in low- and medium-income countries [1]

  • The criteria we used for determining the antiproliferative, as well as cytotoxic effects of crude extracts, has been established by the United States National Cancer Institute, which stipulates that an extract may be considered promising when searching for activity if the IC50 is less than 30 μg/mL in a screening assay [20]

  • The high concentrations (100 μg/mL) of the ethanol leaf extract were able to significantly (P ≤ 0:05) inhibit cell growth of the cancer cell line when compared with control (Figure 1)

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Summary

Introduction

The World Health Organization estimated cancer deaths to be over 9.6 million in 2018, with most of these deaths in low- and medium-income countries [1]. The cost of cancer treatment is beyond the reach of most cancer patients in Zimbabwe. Though access to medical care is generally poor, the situation for cancer patients is worse due to minimal health facilities offering cancer treatment. It is estimated that in Zimbabwe, 17 465 cancer cases were diagnosed in 2018 alone [1]. Leukemic cell lines represent an essential instrument for the biological characterization of human leukaemia. Jurkat-T cells are an IL-2 producing T lymphocyte cell line, BioMed Research International shown to express T cell characteristics and complement receptors [2]. Jurkat-T cells are easy to culture, and grow rapidly, and can be used in human immunodeficiency virus research, though they are contaminated by previously undetected retroviruses [3]

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