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Background: Cancer is a major cause of death worldwide. Limitations of current cancer therapies necessitate the search for new anticancer drugs. Plants represent an immeasurable source of bioactive compounds for drug discovery. The objective of this study was to assess the anti-proliferative and antioxidant potential of four indigenous South African plants commonly used in traditional medicine. Materials and Methods: The anti-proliferative activity of the plant extracts were assessed by the 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2 H -Tetrazolium-5-Carboxanilide (XTT) assay on A431; HaCat; HeLa; MCF-7 and UCT-Mel 1 cells and sulforhodamine-B (SRB) assay on HCT-116 and HCT-15 cell lines. Antioxidant activity was determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide scavenging assays. Results: Three of the plant extracts ( Combretum mollefruit , Euclea crispa subsp. crispa leaves and stems and Sideroxylon inerme leaves and stems showed anti-proliferative activity on the A431 cells with IC 50 values ranging between 26.9 - 46.7 μg/ml. The Euclea crispa subsp. crispa extract also showed anti-proliferative activity on the MCF-7 cell line (45.7 μg/ml). All of the plant extracts ( Combretum molle leaves and fruit, Euclea crispa subsp. crispa leaves and stems, Sideroxylon inerme leaves and stems and Terminalia prunioides leaves and stems) showed DPPH scavenging activity with IC 50 values ranging from 1.8 μg/ml to 11.5 μg/ml. Conclusion: These results indicate that the active extracts of Combretum molle , Euclea crispa subsp. Crispa and Sideroxylon inerme warrant further investigation to determine the mechanism of anti-proliferative activity against cancerous cells. These plant extracts also show potential for further evaluation in the prevention and treatment of cancer. Keywords: South African plants, Traditional medicine, Anti-proliferative activity, Antioxidant activity

Objective To investigate the stem bark of Sideroxylon inerme L. and its compounds for tyrosinase-inhibition activity and to evaluate the mechanism involved of the most potent compounds in tyrosinase inhibition. Materials and methods Three different extracts (acetone, methanol and dichloromethane) of Sideroxylon inerme L. were evaluated for their inhibitory effect in vitro on the monophenolase and diphenolase activated forms of tyrosinase, using a colorimetric procedure. This test was used for bioactivity-guided isolation of two active compounds using column chromatography and TLC. Active extracts were also investigated for their inhibitory effect on melanogenesis in cultured B16 melanoma cells. Antioxidant activities of the methanolic extract of Sideroxylon inerme and purified compounds were investigated using the 1,2-diphenyl-2-picrylhydrazyl (DPPH) antioxidant assay. The inhibition of tyrosinase activity relative to the inhibition of its activity at the transcriptional level was also studied by determination of the degree of expression of mRNAs for this gene by using extract of Sideroxylon inerme-treated cells (B16F10) and semi-quantitative RT-PCR. Results Methanolic and acetonic extracts of the stem bark of Sideroxylon inerme showed significant inhibition of monophenolase activity (IC50 values of 63 μg/ml and 82 μg/ml, respectively). The methanolic extract also exhibited 37% reduction of melanin content at 6.2 μg/ml in melanocytes without being significantly toxic to the cells. Examination for inhibition of monophenoloxidase in situ on TLC, followed by column chromatographic purification of the stem bark extract of Sideroxylon inerme, resulted in the isolation of two active compounds, epigallocatechin gallate and procyanidin B1, with IC50 values against monophenolase of 30 μg/ml and >200 μg/ml, respectively. Epigallocatechin gallate exhibited a greater anti-tyrosinase activity than arbutin. Sideroxylon inerme bark extracts, epigallocatechin gallate and procyanidin B1 exhibited antioxidant DPPH radical scavenging activities with EC50 values of 1.54 μg/ml, 1.33 μg/ml and 1.68 μg/ml, respectively and were not particularly cytotoxic. During mechanism studies it was evident that at the transcription level, Sideroxylon inerme (25 μg/ml) was acting as a potent tyrosinase inhibitor compared to controls (untreated cells and kojic acid). Conclusion The bark extract of Sideroxylon inerme and the two isolated compounds warrant further investigation in clinical studies to be considered as skin-depigmenting agents.