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Alpha tocopheryl succinate inhibits melanocyte-stimulating hormone (MSH)-sensitive adenylate cyclase activity in
S N Sahu1, J Edwards-Prasad, K N Prasad
1Deparment of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Abstract:
D-alpha tocopheryl succinate (vitamin E succinate), which is known to induce differentiation and growth inhibition in murine B-16 melanoma cells, reduced basal and melanocyte-stimulating hormone (MSH)-stimulated adenylate cyclase (AC) activity in vitro. Vitamin E succinate treatment also reduced sodium fluoride- and forskoline-stimulated AC activity of melanoma cells in vitro. Treatment of cells with vitamin E succinate (6 micrograms/ml] for a period of 24 hours was sufficient to reduce MSH-stimulated AC activity. Other forms of vitamin E, such as d1-alpha tocopheryl nicotinate, d1-alpha tocopheryl acetate, and d1-alpha tocopherol, which did not affect growth or morphology of melanoma cells, were relatively less effective in altering basal and MSH-stimulated AC activity. Retinoic acid, which inhibited the growth of B-16 melanoma cells, also reduced basal and MSH-, NaF-, and forskolin-stimulated AC activity in vitro. Prostaglandin A2, which inhibited growth and altered morphology, did not change basal or MSH-stimulated AC activity. These results show that one of the mechanisms of action of vitamin E succinate and retinoic acid on melanoma cells may involve reduction of basal and MSH-sensitive AC activity, and this vitamin effect is not necessarily related to growth inhibition.
Insights
Vitamin E succinate and retinoic acid reduce melanoma cell adenylate cyclase activity, a key mechanism potentially independent of growth inhibition. This finding offers insights into melanoma treatment strategies.
Area of Science:
- Biochemistry
- Cell Biology
- Dermatology
Background:
- D-alpha tocopheryl succinate (vitamin E succinate) is known to induce differentiation and inhibit growth in B-16 melanoma cells.
- Melanocyte-stimulating hormone (MSH) plays a role in melanoma cell activity.
Purpose of the Study:
- To investigate the effect of vitamin E succinate on adenylate cyclase (AC) activity in melanoma cells.
- To explore the mechanism of action of vitamin E succinate and retinoic acid on melanoma cells.
Main Methods:
- In vitro studies using murine B-16 melanoma cells.
- Measurement of basal, MSH-, sodium fluoride-, and forskolin-stimulated AC activity.
- Treatment with vitamin E succinate, other vitamin E forms, retinoic acid, and prostaglandin A2.
Main Results:
- Vitamin E succinate significantly reduced basal and MSH-stimulated AC activity.
- Other vitamin E forms showed less impact on AC activity.
- Retinoic acid also reduced AC activity, while prostaglandin A2 did not.
Conclusions:
- Vitamin E succinate and retinoic acid may exert their effects on melanoma cells by reducing basal and MSH-sensitive AC activity.
- This reduction in AC activity is not necessarily linked to growth inhibition.