alpha-Tocopherol enhances tumour growth inhibition by cis-dichlorodiammine platinum (II)

Abstract

Present studies indicate that a-tocopherol enhances the efficacy of cisplatin as demonstrated by inoculation of Daltons lymphoma cells incubated with either cisplatin (5 or 10 µg/ml) alone or cisplatin + atocopherol (25 or 50 µg/ml) into C3H/He mice. Tumour cells (3 x 10 6 cells/mouse) incubated with cisplatin grow slowly in syngeneic mice as indicated by the late appearance of tumour. However, mice failed to develop tumour when inoculated with tumour cells incubated with cisplatin + a-tocopherol. When the animals were challenged with tumour cells (3 x 10 6 cells/mouse) on the 15th day after the initial inoculation, 30-50% survived more than 60 days, with 10% tumourfree survivors being observed in some groups. Antitumour activity was higher in mice receiving lymphoma cells (3 x 10 6 cells/mouse) preincubated with cisplatin + a-tocopherol compared to cisplatin alone. Tumour-bearing mice receiving cisplatin in combination with different concentrations of a-tocopherol exhibited significantly higher (P<0.001) intratumour platinum content (123-306%) but without any change in the kidney platinum content as compared to those receiving cisplatin (5 or 10 µg/ml) alone. Enhancement of cisplatin-induced tumour growth inhibition is probably due to the modulation of tumour cell membrane permeability by a-tocopherol. a-Tocopherol might increase the influx of cisplatin into tumour cells, causing the DNA repair machinery to be less efficient due to increased efficiency of adduct formation in the DNA molecule. This effect of a-tocopherol can render cisplatin more effective as an antitumour agent. Correspondence

α‐tocopherol protects against cisplatin‐induced toxicity without interfering with antitumor efficacy

“…Moreover, tumor growth in mice treated with the combination DDP and α‐tocopherol was similar to that observed in mice treated with DDP as a single agent. These results appear to disagree with those reported by Sarna et al ,13 who demonstrated that α‐tocopherol enhanced antitumor activity on lymphoma cells both in vitro and in vivo by increasing the influx of DDP in tumor cells. The difference between these results and our data may be due to the higher doses of α‐tocopherol employed than those used in our study.…”

“…In colon cancer cells, while α‐tocopherol has very little effect on cell growth and differentiation in vitro , the redox‐inactive analogue α‐tocopheryl succinate, a strong inductor of apoptosis, shows high antitumor activity 11. Moreover, it has been reported that α‐tocopherol and α‐tocopheryl succinate enhance tumor growth inhibition in combination with DDP 12, 13, 14. Regardless of these results, α‐tocopherol, because of its antioxidants properties, might interfere with the antitumor activity of DDP, which also exerts its effect by producing ROS.…”

The protective effects of intratympanic dexamethasone and vitamin E on cisplatin-induced ototoxicity are demonstrated in rats

“…Significant difference in response to cisplatin chemotherapy with or without combined administration of vitamin E [35]. Sarna et al found enhanced tumor growth inhibition in mice with lymphoma when the animals were receiving vitamin E and cisplatin [36].…”

Vitamin E Reduces Cisplatin Ototoxicity

“… 27 In preclinical trials in nude mice xenografted with human melanoma, there was no significant difference in response to cisplatin chemotherapy with or without combined administration of vitamin E. 28 A similar response was noted in clinical trials when comparing patients treated with cisplatin with or without vitamin E. 28 Sarna et al 29 found enhanced tumor growth inhibition in mice with lymphoma when the animals were receiving vitamin E and cisplatin. 29 A diet rich in several antioxidants, which included vitamin E, was able to slow the growth rate of lung carcinoma in mice receiving cisplatin. 30 Enhanced antitumor activity of cisplatin against neuroblastoma in mice receiving vitamin E was reported.…”