Objective Plants are considered as primary resources for the producing effective drugs in the treatment of cancer owing to the possession of active compounds. Almond hulls -AlH-, as an agricultural waste material, contain a high level of polyphenols and possess remarkable antioxidant. Considering the anti-cancer effects of antioxidants, it was hypothesized that AlH extract has cytotoxic effect against tumor cells. Materials and Methods The total phenolic and flavonoid content of AlH were evaluated by the FolineCiocalteu assay and aluminum chloride reagent, respectively. Antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl -DPPH-. The identification of compounds was performed by Gas chromatography–mass spectrometry -GC-MS-. Cells viability was evaluated by -3--4,5-Dimethylthiazol-2-yl--2,5-diphenyltetrazolium bromide- -MTT- and the mode of cell death was determined by acridine orange and ethidium bromide -Ac/EtBr- staining. Results AlH extract demonstrated a concentration dependent scavenging activity by quenching DPPH radicals with SC50 value of 25 µg/ml. Based on the colorimetric techniques, the total content of phenolic and flavonoid compounds at 0.625 mg/ml were …mg galic/g extract acid and …mg catechin/g extract, respectively. GC-MS analyses showed that almond hull extract contains phenolic compounds such as methoxysalcylic acid, 2,6 dimethyl phenol, and sinapic acid and flavonoid compounds such as quercetin and catechin. MTT assay revealed that almond hull extract inhibited the proliferation of osteosarcoma calls -Saos-2- in a concentration dependent manner. IC50 value was calculated 123.7 µg/ml. Cell cycle analyses showed that more than 19% of treated cells were arrested in G2/M phase as compared with that in untreated sample -14%-. Moreover, it has been revealed that the reduction in the proliferation is accompanied with the cell death. Ac/EtBr staining demonstrated that the apoptosis is a dominant mode of cell death in AlH-treated cells. Conclusion The results showed that AlH has high antioxidant activity and cytotoxic effects against osteosarcoma cells. Therefore, AlH could be considered as an candidate for the treatment of cancer, however further elaborate investigations are required to establish the in vivo efficacy of AlH.

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