pinosylvin and Lung-Neoplasms

Metastasis is a major cause of death in cancer patients. Our previous studies showed that pinosylvin, a naturally occurring trans-stilbenoid mainly found in Pinus species, exhibited a potential cancer chemopreventive activity and also inhibited the growth of various human cancer cell lines via the regulation of cell cycle progression. In this study, we further evaluated the potential antimetastatic activity of pinosylvin in in vitro and in vivo models. Pinosylvin suppressed the expression of matrix metalloproteinase (MMP)-2, MMP-9 and membrane type 1-MMP in cultured human fibrosarcoma HT1080 cells. We also found that pinosylvin inhibited the migration of HT1080 cells in colony dispersion and wound healing assay systems. In in vivo spontaneous pulmonary metastasis model employing intravenously injected CT26 mouse colon cancer cells in Balb/c mice, pinosylvin (10 mg/kg body weight, intraperitoneal administration) significantly inhibited the formation of tumor nodules and tumor weight in lung tissues. The analysis of tumor in lung tissues indicated that the antimetastatic effect of pinosylvin coincided with the down-regulation of MMP-9 and cyclooxygenase-2 expression, and phosphorylation of ERK1/2 and Akt. These data suggest that pinosylvin might be an effective inhibitor of tumor cell metastasis via modulation of MMPs.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chemoprevention; Colonic Neoplasms; Cyclooxygenase 2; Humans; Lung Neoplasms; Male; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Phosphorylation; Stilbenes

The leaves of the Japanese Alnus sieboldiana have been extracted with n-hexane and then with methanol. A bioactivity-guided approach based on MTT assay for growth inhibition and quantitative real-time PCR for TNF-α inhibitory activity was taken to identify the active compounds in EtOAc soluble fraction of the methanol extract. From this active fraction, seven compounds have been isolated and four compounds (pinosylvin, galangin, quercetin and methyl gallate) have been examined for their dose-response effect on the viability of A549 cells and on TNF-α inhibitory activity. Based on MTT assay, all of the four examined compounds inhibit growth of human lung cancer cells. Among four tested compounds only galangin (3,5,7-trihydroxyflavone) significantly inhibited TNF-α gene expression in A549 cells (IC₅₀ = 94 μM). Taken together, this finding suggests that galangin may be useful in cancer prevention.

Topics: Alnus; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Dose-Response Relationship, Drug; Flavonoids; Gallic Acid; Humans; Lung Neoplasms; Phytotherapy; Plant Extracts; Plant Leaves; Quercetin; Stilbenes; Tumor Necrosis Factor-alpha