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The Center For The Improvement Of Human Functioning International
A Non-profit Medical, Research and Educational Organization
3100 North Hillside Avenue, Wichita, KS 67219 USA
Phone: 316-682-3100; Fax: 316-682-5054
Cytotoxicity
of Ascorbate, Lipoic Acid, and Other Antioxidants In Hollow Fibre In
Vitro Tumors
By J.P. Casciari, N.H. Riordan, T.L. Schmidt, XL Meng, J.A. Jackson and
H.D. Riordan, from British Journal of Cancer (2001) 84:11, 1544-1550
Abstract
Vitamin C (ascorbate) is toxic to tumour cells,
and has been suggested as an adjuvant cancer treatment. Our goal was
to determine if ascorbate, in combination with other antioxidants, could
kill cells in the SW620 hollow fibre in vitro solid tumour model at
clinically achievable concentrations. Ascorbate anti-cancer efficacy,
alone or in combination with lipoic acid, vitamin K3, phenyl ascorbate,
or doxorubicin, was assessed using annexin V staining and standard survival
assays. 2-day treatments with 10mM ascorbate increased the percentage
of apoptotic cells in SW620 hollow fibre tumours.
Lipoic acid synergistically
enhanced ascorbate cytotoxicity, reducing the 2-day LC50 in hollow fibre
tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally
effective against proliferating and nonproliferating cells. Ascorbate
levels in human blood plasma were measured during and after intravenous
ascorbate infusions. Infusions of 60 g produced peak plasma concentrations
esceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus,
tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy
was enhanced in an additive fashion by phenyl ascorbate or vitamin K3.
The effect of ascorbate on doxorubicin efficacy was concentration dependent;
low doses were protective while high doses increased cell killing. ©
2001 Cancer Research Campaign http://www.bjcancer.com
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