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

Abstract

Summary 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 K 3 , phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC 50 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 exceeding 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 K 3 . The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing.

Intravenously administered vitamin C as cancer therapy: three cases

“…Concentrations of 1000-5000 µmol/L are selectively cytotoxic to tumour cells in vitro, [16][17][18][19][20] and emerging evidence indicates that ascorbic acid at concentrations achieved only by the intravenous route may function as a pro-drug for hydrogen peroxide delivery to tissues. 20 The in vitro biologic evidence and clinical pharmacokinetics data confer biological plausibility to the notion that vitamin C could affect cancer biology and may explain in part the negative results of the Mayo Clinic trials.…”

Gene expression response to ascorbic acid in mice implanted with sarcoma S180 cells

“…Ascorbate plays a role in limiting inflammation, regulating cytokine production, and boosting the immune system [2][3][4][5][6][7][8]. It has a variety of properties that have generated interest in using it against cancer [9][10][11][12][13]: it enhances natural killer cell activity [14,15], increases collagen synthesis [16], inhibits capillary tubule formation (angiogenesis) [17,18], reduces inflammation in cancer patients [3], at millimolar concentrations, shows cytotoxicity against cancer cells [19][20][21][22][23][24] and the ability to reduce tumor growth in vivo [25][26][27][28][29][30][31][32][33][34]. Clinical trials to date [35][36][37][38][39][40] indicate that high dose (on the order of ten to 100 grams) intravenous ascorbate therapy can enhance anti-cancer effects of chemotherapy and improve quality of life in cancer patients.…”

The Influence of a Combination of Antioxidants on Sub Fertile Male Rat.

“…While the gain weight of male rats does not agree with what (31) reported its affect to decreases weight gain and obesity. For the sperm count and live sperms percentage ALA and COMB were found significantly different than other groups due to the effect of ALA in strengthens other antioxidant effect which was obvious on the combination of few antioxidants (32) in producing more live sperms and this effect was seen more and clear on agglutinations of sperm in ALA and COMB group while less in abnormal sperm percentage was seen in CAR group which is may due to (33) in scavenging free radicals Maintaining mitochondria integrity in stress conditions and preventing ROS formation.…”