nsc-4347 and Neoplasm-Metastasis

Recently many studies showed anticancer activities of piperine, a pungent alkaloid found in black pepper and some other Piper species. We attempted to summarize acquired data that support anticancer potential of this natural agent. Piperine has been reported to possess effective chemopreventive activity. It has been studied to affect via several mechanisms of action, in brief enhancing antioxidant system, increasing level and activity of detoxifying enzymes and suppressing stem cell self-renewal. Moreover, piperine has been found to inhibit proliferation and survival of various cancerous cell lines via modulating cell cycle progression and exhibiting anti-apoptotic activity, respectively. This compound has been shown to modify activity of various enzymes and transcription factors to inhibit invasion, metastasis and angiogenesis. Interestingly, piperine has exhibited antimutagenic activity and also inhibited activity and expression of multidrug resistance transporters such as P-gp and MRP-1. Besides, about all reviewed studies have reported selective cytotoxic activity of piperine on cancerous cells in compared with normal cells. Altogether, the studies completely underline promising candidacy of piperine for further development. The collected preclinical data we provided in this article can be useful in the design of future researches especially clinical trials with piperine.

Topics: Alkaloids; Animals; Anticarcinogenic Agents; Antimutagenic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Benzodioxoles; Biological Availability; Cell Proliferation; Cell Survival; Drug Evaluation, Preclinical; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Inactivation, Metabolic; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Piper; Piperidines; Polyunsaturated Alkamides; Stem Cells

To investigate the effects of piperine, a major pungent alkaloid present in Piper nigrum and Piper longum, on the tumor growth and metastasis of mouse 4T1 mammary carcinoma in vitro and in vivo, and elucidate the underlying mechanisms.. Growth of 4T1 cells was assessed using MTT assay. Apoptosis and cell cycle of 4T1 cells were evaluated with flow cytometry, and the related proteins were examined using Western blotting. Real-time quantitative PCR was applied to detect the expression of matrix metalloproteinases (MMPs). A highly malignant, spontaneously metastasizing 4T1 mouse mammary carcinoma model was used to evaluate the in vivo antitumor activity. Piperine was injected into tumors every 3 d for 3 times.. Piperine (35-280 μmol/L) inhibited the growth of 4T1 cells in time- and dose-dependent manners (the IC(50) values were 105 ± 1.08 and 78.52 ± 1.06 μmol/L, respectively, at 48 and 72 h). Treatment of 4T1 cells with piperine (70-280 μmol/L) dose-dependently induced apoptosis of 4T1 cells, accompanying activation of caspase 3. The cells treated with piperine (140 and 280 μmol/L) significantly increased the percentage of cells in G(2)/M phase with a reduction in the expression of cyclin B1. Piperine (140 and 280 μmol/L) significantly decreased the expression of MMP-9 and MMP-13, and inhibited 4T1 cell migration in vitro. Injection of piperine (2.5 and 5 mg/kg) dose-dependently suppressed the primary 4T1 tumor growth and injection of piperine (5 mg/kg) significantly inhibited the lung metastasis.. These results demonstrated that piperine is an effective antitumor compound in vitro and in vivo, and has the potential to be developed as a new anticancer drug.

Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Benzodioxoles; Breast; Breast Neoplasms; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Mammary Neoplasms, Experimental; Matrix Metalloproteinase 13; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Piper; Piperidines; Polyunsaturated Alkamides