retinaldehyde and Melanoma

Disturbances in vitamin A metabolism are an important attribute of some cancer cells. Most evidence point that these disturbances lead to decreasing of the retinoic acid concentration in tumor cells. Up to now, in benign and malignant skin cells the features of vitamin A metabolism with its participating enzymes are not entirely understood. Alcohol and aldehyde dehydrogenases (ALDH) are involved in the retinol metabolism, oxidizing retinol, and retinal in retinoic acid or reducing retinal in retinol. In this work we investigated the expression and enzymatic activity of alcohol and ALDH in melanoma cells compared to their benign counterparts. We demonstrated that melanoma cell lines and melanocytes despite similar pattern of the enzyme expression, show different general ALDH activity. Retinal, the substrate of ALDH, could stimulate the ALDH activity through up-regulation of retinaldehyde dehydrogenase 1 and aldehyde dehydrogenase 6. Furthermore, we found that retinoids regulate alcohol dehydrogenase activity, probably via effects on alcohol dehydrogenase expression at the post-transcriptional level. We suggest that melanoma cells in contrast to melanocytes should favor the retinal reduction over its oxidation. The decreasing cellular amount of the precursor molecules of retinoic acid could result in a changed gene regulation in melanoma cells.

Topics: Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Cell Line; Cell Line, Tumor; Humans; Melanocytes; Melanoma; Retinaldehyde; RNA, Messenger

Growth cessation and cell death of exponentially proliferating Harding-Passey melanoma cells (HPM-73 line) in monolayer culture resulted in the presence of 3.3 X 10(-5) M retinal, while retinol and retinoic acid caused growth retardation at 3.3 X 10(-5) M. Also at 1 X 10(-5) M, the growth-inhibitory effect of retinal was more pronounced than that of retinol or retinoic acid. Following serum removal from the culture media, all 3 retinoids at 3.3 X 10(-6) M or 1 X 10(-5) M revealed cytotoxic effects within 3 days as demonstrated by cell loss from the substratum. Thus, the presence of serum has "protective" effects. Addition of retinal, retinoic acid or retinol at 1 X 10(-5) M to cultures in stationary growth phase did not result in cell loss during period of 6 days. C57Bl mice with B16 melanotic melanoma were i.p. injected during 10 days with retinoids (30 or 100 mcg per mouse daily). All retinoids inhibited B16 tumor growth in vivo. In this respect, retinoic acid was the most effective one. The cellular melanin content of cultured HPM-cells and of B16 melanotic melanoma in vivo was elevated after treatment with retinoids; retinal having the strongest effect.

Topics: Animals; Cell Line; In Vitro Techniques; Melanins; Melanoma; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Retinaldehyde; Retinoids; Stimulation, Chemical; Tretinoin; Vitamin A

A new, water-soluble, polymer-linked form of retinal was synthesized and tested for its ability to support the growth of vitamin A-deficient noninbred Holtzman rats and to inhibit the proliferation of melanoma cells in culture. Retinal was conjugated to the hydrazide of carboxymethyldextran in the presence of alpha-and beta-cyclodextrins. The aqueous solutions of the product contained between 200 and 1,000 micrograms retinal/ml as opposed to the low water solubility (< 0.01 micrograms/ml) of retinal itself. The retinal-dextran complex, although barely resorbed from the gastrointestinal tract, supported the growth of rats fed a vitamin A-deficient diet when administered ip at 2.3 mumol of retinal equivalent/kg body weight. Retinal and the retinal-dextran complex exhibited differential cytotoxicity toward S91 melanoma cells and caused cell lysis at 10 and 500 microM (retinal residue), respectively. At noncytotoxic doses both free retinal and its dextran-linked derivative reduced the cell proliferation rate in a time- and dose-dependent fashion with median inhibitory doses of 1 and 4 microM (retinal residue), respectively. These data demonstrated that the water-soluble retinal-dextran complex retained certain biologic activities of retinal and was less cytotoxic.

Topics: Animals; Cell Division; Cell Line; Cells, Cultured; Dextrans; Dose-Response Relationship, Drug; Male; Melanoma; Mice; Rats; Retinaldehyde; Vitamin A; Vitamin A Deficiency