In vitro anti-proliferative effects of an isoflavonoid on HO-1 human melanoma cells.

摘要

Polyphenols abundantly occur in the plant kingdom and may play an important role in cancer treatment. Their cancer prevention abilities are due to their interaction with basic cellular mechanisms. Such interactions may include inhibition of proliferation, modulation of signaling cascades, interaction with basic enzymes involved in tumor promotion and metastasis. In this experiment, the influence of a newly synthesized Isoflavonoid, 7-dimethylallyloxy-2-methyl isoflavone, which will refer to as VSP-29, was investigated in HO-1 human melanoma cancer cells by evaluating cell proliferation, viability, and melanin production as a marker for differentiation. Additionally a RT-PCR screen of 180 genes associated with Human Signal Transduction and Human Apoptosis was performed.;The treatment with a single dose of VSP-29 at sub microgram/ml levels decreased cell proliferation without affecting viability as determined by the Trypan blue exclusion method. A single treatment of VSP-29 stimulated cell dendricity, a morphological feature of differentiated melanocytes. VSP-29 produced a decrease in proliferation after 48 and 72 hour treatment. This effect was also observed after the removal of VSP-29 at the 24-hour treatment time point. The results of melanin assay showed that VSP-29 treatment induced melanin production in HO-1 cells. The PCR arrays gene regulation results inferred that, TRAF-mediated JNK pathway, one kind of mitogen-activated protein kinase (MAPK) pathway may be involved in the mechanism of action of VSP-29 on HO-1 cells. Cells may respond to environmental stress with activation of c-Jun N-terminal kinase (JNK) and subsequently can activate transcription factor Activator Protein-1(AP-1) which has been shown to play a role in cell proliferation, differentiation, cell migration and apoptosis. This conclusion made on the basis of the few observed up-regulated genes on both the arrays and their presence in the cascade.