Abstract:
:The present study was conducted to clarify the mechanism responsible for enhancement of the anti-melanoma activity of levodopa methylester by supplemental ascorbate in vivo. 5-Hydroxydopa, a known cytotoxic agent and the major metabolite formed from levodopa in the presence of ascorbate and mushroom tyrosinase in vitro, was assessed for its antitumor activity against i.p. and s.c. inoculated B16 melanoma, P388 leukemia, and L1210 leukemia in mice with and without supplemental ascorbate. Treatment with 5-hydroxydopa failed to significantly increase survival of mice bearing i.p. or s.c. pigmented and non-pigmented B16 melanomas even though it inhibited local tumor growth. Treatment increased survival of both P388 and L1210 leukemias, and this increase was more pronounced in mice bearing i.p. tumors than in mice bearing s.c. tumors. This treatment significantly decreased final tumor weight of both leukemias implanted s.c., and inhibited ascites formation in mice inoculated with i.p. tumors. Ascorbate supplementation decreased or abrogated the effect of 5-hydroxydopa on survival in mice bearing i.p. or s.c. leukemia tumors and decreased survival relative to control mice bearing i.p. or s.c. pigmented and s.c. non-pigmented tumors. It did not affect survival of treated mice bearing i.p. non-pigmented melanoma tumors. Ascorbate supplementation did not modify the effect of 5-hydroxydopa treatment on primary s.c. tumor growth in mice bearing melanoma or leukemia tumors nor did it affect ascites formation in treated mice bearing i.p. leukemia tumors. The lack of correlation between the observed inhibition of primary tumor growth and the absence of an effect on survival in 5-hydroxydopa treated mice bearing i.p. melanoma may relate to an inability of this drug to interfere with tumor metastasis. These data argue against a role for 5-hydroxydopa as a metabolically derived cytotoxic formed in situ during concurrent treatment with levodopa methylester and supplemental ascorbate.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Pierson HF,Meadows GGdoi
10.1016/0304-3835(85)90154-5subject
Has Abstractpub_date
1985-11-01 00:00:00pages
157-68issue
2eissn
0304-3835issn
1872-7980pii
0304-3835(85)90154-5journal_volume
29pub_type
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