In vitro culture studies of Sutherlandia frutescens on human tumor cell lines

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Abstract

Sutherlandia frutescens is a South African herb used traditionally by the natives to treat cancer, and more recently to improve the overall health in HIV/AIDS patients. Gas chromatography/mass spectrometer profiling and liquid chromatographic/mass spectral investigation confirmed and quantified the presence of canavanine, GABA and arginine in the herbal preparation used in this study. In vitro study demonstrated a concentration dependent effect of Sutherlandia on several tumor cell lines, with 50% inhibition (IC50) of proliferation of MCF7, MDA-MB-468, Jurkat and HL60 cells at 1/250, 1/200, 1/150 and 1/200 dilutions, respectively. Sutherlandia treatment did not induce HL60 differentiation along the macrophage/monocyte or granulocyte lineage. It demonstrated antioxidant activity in reducing free radical cations with an estimated activity of 0.5 μl of Sutherlandia extract equivalent to that of 10 μM of Trolox. However, it did not significantly suppress lipopolysaccharide stimulated nitric oxide production by murine macrophage/monocyte RAW 264.7 cells, nor did it significantly inhibit IL-1β and TNF-α mRNA expression in RAW 264.7 cells. In conclusion, Sutherlandia ethanolic extract showed a concentration dependent antiproliferative effect on several human tumor cell lines but did not show significant antioxidant effects. Further studies are needed to explore the activities of this multipurpose South African herbal preparation.

Introduction

Sutherlandia frutescens (unwele in Zulu; kankerbos in Afrikaans; cancer bush in English), a member of the pea family, is a shrub with attractive flowers used traditionally by South Africans to treat a variety of maladies. The medicinal use probably originated with the Khoi and Nama people; who used decoctions externally to wash wounds and internally for fevers and a variety of other ailments. It is an old Cape remedy for stomach problems and internal cancers (van Wyk et al., 1997, van Wyk and Gericke, 2000). The leaves are mainly used, but all above-ground parts are usually included. Recent anecdotal reports from South African doctors and healthcare workers described positive effects of a herbal preparation of the plant on HIV patients (Morris, 2001). In view of the fact that the herbal preparation was reported to be safe and inexpensive, and has great potential to improve the quality of life of a large population of HIV/AIDS patients in the African continent, the South African Medical Research Council is conducting a pilot clinical trial of the preparation on HIV patients (WHO Press Release, 2002). According to the manufacturer, there is preliminary clinical evidence that Sutherlandia has a direct anticancer effect on some cancers, and also has immunostimulant properties.

The limited available information in the literature showed that Sutherlandia leaves contain several biological active chemicals including canavanine, a non-protein α-amino acid, pinitol and GABA. The plant also contains amino acids, small amounts of saponins but no alkaloids (van Wyk et al., 1997). Canavanine and its major metabolite canaline have anti-tumor properties and are being developed as new anticancer drugs (Crooks and Rosenthal, 1994). Despite the fact that Sutherlandia frutescens has enjoyed a long history of use by all cultures in Southern Africa, there are at present no reported studies in the peer-reviewed literature, of either in vitro or animal studies, its effects on cancer cells. The purpose of this study was to investigate the in vitro activities of Sutherlandia including the antiproliferative, antioxidant, and differentiation inducing properties on several cancer cell lines.

Section snippets

Plant material and preparation of extract

Two different samples of Sutherlandia frutescens preparation (#5126) were purchased from PhytoNova (Cape Town, South Africa). PhytoNova indicated each Sutherlandia tablet contains 300 mg of raw herb powder compounded with inert excipients. For cell culture studies, each tablet was extracted with 2.2 ml of 70% EtOH at room temperature for 2 h on an orbital shaker. The suspension was centrifuged at 5000×g for 10 min and the supernatant was removed. This extract was further diluted to 1/100, 1/200,

Gas chromatography/mass spectrometer profiling

The chromatogram in Fig. 1A is the result of GC/MS analysis. Mass spectral investigation resulted in identification of the prominent peaks of methyl paraben (8.25 min), propyl paraben (9.43 min), hexadecanoic acid (12.02 min), gamma sitosterol (22.31 min), and sigmast-4-en-3-one (23.37 min). Both methyl and propyl parabens are normally utilized as preservatives while the other identified compounds are common compounds present in the plants. Peaks at 19.30, 20.23 and 20.58 min were tentatively

Discussion

Large varieties of herbal products are available in natural health product stores as dietary supplements for cancer patients. Even though many of them have been used traditionally for cancer treatment for a long time, few peer-reviewed reports are available about their efficacy, active principles, mode of action, side effects, and possible adverse interactions with conventional antitumor drugs. Therefore testing of herbal agents in vitro on cancer cell lines to understand their mechanism of

Acknowledgements

This work was supported by Lotte and John Hecht Memorial Foundation and Tzu Chi Foundation. Technical support from Christopher Lowe is greatly appreciated.

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