One of the approaches to control cancer is prevention through consumption of fruits and vegetables which are associated with a reduced risk of cancer. The present study was undertaken to examine the chemopreventive effects of Streblus asper root extracts on osteosarcoma (HOS) and tongue carcinoma (SCC-15) cells' growth, cell cycle modulation, apoptosis induction, and associated molecular alterations in vitro . S. asper root extract treatment on HOS and SCC-15 cells resulted in a signi fi cant decreased in cell growth with IC 50 value of 0.3 and 1%, respectively which was associated with the cell cycle phase arrest and the induction of apoptosis. Cell cycle analysis showed G2/M phase arrest in HOS and G0/G1 phase arrest in SCC-15 cells following treatment with S. asper root extracts for 72 h. This S. asper -mediated cell cycle arrest in HOS cells was accompanied with a decrease in protein levels of phosphorylated ERK ½. Induction of apoptosis was characterized by the appearance of cells with sub-G1 DNA content and the cleavage and activation of caspase 3, caspase 9 and Bcl-2 proteins. Treatment with S. asper root extract also resulted in alterations of cell morphology including cell shrinkage, vacoularization, and membrane blebbing. These fi ndings show that S. asper modulates caspase A. Seeni (*) Toxicology Cluster , Advanced Medical and Dental Institute, Universiti Sains Malaysia , No 6 Tingkat 1 (Lot 13), Persiaran Seksyen 4/9,

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Epidemiological studies have demonstrated a positive correlation between consumption of vegetables, fruits and beverages with reduced risk of cancer. It is estimated there are around 8,100 plant species in the Malaysian rain forests, with 10% of them reported to have some medicinal value. However, to date in Malaysia, not much investigation has been done on chemopreventive activities on cancer although Malaysian plants are an exclusive source of effective chemopreventive agents and therefore, this background leads to the premise that our local plants such as Streblus asper could have greater potential for the chemoprevention activities. Streblus asper is well known as an expensive bonsai plant which is indigenous to tropical countries such as Malaysia, Thailand, Sri Lanka and India. It is used traditionally in leprosy, piles, diarrhea, dysentery, elephantiasis and cancer. It finds place in Ayurvedic Pharmacopoeia of India and also been described in some monographs, but none have reported its activity as chemopreventive agents and the underlying mechanisms remain unclear. In the present study, we try to identify its biological properties and the cytotoxicity effect on normal liver and kidney cells. Using the osteosarcoma cells as our in vitro model, the IC50 of Streblus asper root extract was determined and observed its effect on the osteosarcoma cells morphology that changes within time, the anti-proliferative pattern and live-death analysis under confocal microscope analysis. The results showed that the root extracts did not contained any heavy metals compound such as mercury and cadmium and with less arsenic (0.02 ppm) and plumbum (0.07 ppm) and showing non-cytotoxic effect on vero cells (normal kidney cells) and WRL-68 cells (normal liver cells). Our HPLC profiling analysis also revealed antioxidants compounds exist in the Streblus asper root extracts such as caffeic acid which has been shown to act as a carcinogenic inhibitor. Although the low-level of anti-oxidants been found from the extracts but it still can inhibit the growth of the osteosarcoma cells which also exert apoptosis features like cell shrinkage (atrophy) and vocalization in time and dose-dependent manner. The plant extracts IC50 doses was at 0.05% of root extracts and it also demonstrated the anti-proliferative effect by suppressed the cells growth as early as 12 hours of treatment and marked cell death till day 6. On live-death analysis under confocal microscope using Calcein and Ethidium staining confirmed that Streblus asper root extract exert cell death to osteosarsoma cells. This study is just a preliminary study as to identify its pharmacological properties on carcinogenesis and further investigation is still on-going to develop it as the chemopreventive agent especially to determine the signaling pathway involved. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B73.