Anti-metastatic effect of Biophytum sensitivumis exerted through its cytokine and immunomodulatory activity and its regulatory effect on the activation and nuclear translocation of transcription factors in B16F-10 melanoma cells
Chandrasekharan Guruvayoorappan and Girija Kuttan
The major clinical challenge for cancer therapy remains the eradication or prevention of metastatic process. This study was an investigation of the antimetastatic activity of Biophytum sensitivum, using B16F-10 melanoma-induced experimental lung metastasis in C57BL/6 mice. B. sensitivum treatment significantly reduced lung tumor nodule formation accompanied by reduced lung collagen hydroxyproline, hexosamine, and uronic acid levels. Serum sialic acid and gamma-glutamyl transpeptidase levels were also significantly inhibited after B. sensitivum treatment. B. sensitivum treatment down-regulated the expression of matrix metalloprotease-2 and -9 and at the same time up-regulated the lung tissue inhibitor of metalloprotease-1 and -2 expression. The cytokine profile and growth factors such as interleukin-1b, interleukin-6, tumor necrosis factor-a, granulocyte monocyte-colony stimulating factor, vascular endothelial growth factor, interleukin-2 and tissue inhibitor of metalloprotease-1 in the serum of these animals were markedly altered after B. sensitivum treatment. This altered level of cytokines after B. sensitivum treatment was also accompanied by enhanced natural killer cell and antibody-dependent cellular cytotoxicity. The study reveals that B. sensitivum treatment could alter proinflammatory cytokine production and could inhibit the activation and nuclear translocation of p65, p50, c-Rel subunits of nuclear factor-kB, and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein in B16F-10 melanoma cells.
Keywords: Biophytum sensitivum; Metastasis; Hydroxyproline; Cytokines; Nuclear factor-kB; Activated transcription factor