Effect of Withania somnifera on B16F-10 melanoma induced metastasis in mice

Withania somnifera, a plant with known immunopotentiating activity and its bioactive fraction-Withanolide D were studied for their anti-metastatic activity using B16F-10 melanoma cells in C57BL/6 mice. Simultaneous administration of Withania extract (122 +/- 10 tumour nodules) and Withanolide (126 +/- 9 lung tumour nodules) could significantly (p < 0.001) inhibit the metastatic colony formation of the melanoma in lungs. 72.58% by extract and 69.84% by Withanolide treated, as compared to the untreated control animals also increased the survival days. Lung collagen hydroxyproline content was highly elevated in the control animals (23.5 +/- 0.9 mug/mg protein), which was reduced by the simultaneous administration of both the extract (16.3 +/- 2.0 mug/mg protein) and Withanolide (15.3 +/- 1.8 mug/mg protein). The level of lung hexosamines (4.85 +/- 0.20 mg/ 100 mg tissue) and uronic acids (330.1 +/- 23.7 mug/100 mg tissue) content was also elevated in the control animals. The elevated level of hexosamine was significantly reduced by the treatment with extract (1.92 +/- 0.05) and Withanolide (1.85 +/- 0.05). Similarly, the uronic acid content was also been reduced by the simultaneous administration of both Withania extract (194.2 +/- 17.4) and Withanolide (183.2 +/- 8.8). The control animals had 35.3 +/- 3.8 U/L gamma-glutamyl transpeptidase (gamma-GT), which was reduced by 50% by the treatment of extract and Withanolide to 17.5 +/- 4.0 U/L and 16.3 +/- 4.4 U/L respectively. There was a significant reduction in the levels of sialic acid in the serum of Withania extract (60.7 +/- 7.7) and Withanolide (67.16 +/- 5.8) treated animals compared to the higher level (102.2 +/- 8.7) in the control animals. Histopathological analysis of the lung tissues also correlated with these findings. Prophylactic administrations of both extract as well as Withanolide were ineffective in inhibiting the metastasis of B16F-10 melanoma cells. Copyright (C) 2004 John Wiley Sons, Ltd.