Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours

Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as a n adjuvant cancer treatment. Our goal was to determine if ascorbate, in com bination with other antioxidants, could kill cells in the SW620 hollow fibr e in vitro solid tumour model at clinically achievable concentrations. Asco rbate anti-cancer efficacy, alone or in combination with lipoic acid, vitam in K-3, phenyl ascorbate, or doxorubicin, was assessed rising annexin V sta ining and standard survival assays. 2-day treatments with 10 mM ascorbate i ncreased the percentage of apoptotic cells in SW620 hollow fibre tumours. L ipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2- day LC50 in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike as corbate, was equally effective against proliferating and nonproliferating c ells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma co ncentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h . Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate eff icacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K- 3. The effect of ascorbate on doxorubicin efficacy was concentration depend ent; low doses were protective while high doses increased cell killing. (C) 2001 Cancer Research Campaign.