RRC ID 37939
Author Narayanan NK, Kunimasa K, Yamori Y, Mori M, Mori H, Nakamura K, Miller G, Manne U, Tiwari AK, Narayanan B.
Title Antitumor activity of melinjo (Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in a colon-26 tumor-bearing mouse model in vivo.
Journal Cancer Med
Abstract Melinjo (Gnetum gnemon L.) seed extract (MSE) and its active ingredient gnetin C (GC), a resveratrol dimer, have been shown to possess a broad spectrum of pharmacological activities. In this study, we investigated the antitumor activity of MSE and GC using human and murine tumor cell culture models in vitro. The antitumor activity of GC was compared with trans-resveratrol (tRV), a stilbenoid polyphenol. Our results show that MSE and GC at clinically achievable concentrations significantly inhibited the proliferation of pancreatic, prostate, breast, and colon cancer cell types (P < 0.05), without affecting normal cells. Interestingly, GC exerts enhanced antitumor activity than that of tRV (P < 0.05). MSE and GC significantly induced apoptosis in all the cancer cells, indicating MSE and GC inhibit tumor cell growth by inducing apoptosis (P < 0.001). Our findings provide evidence that MSE might induce apoptosis in cancer cells via caspase-3/7-dependent and -independent mechanisms. However, GC might trigger both early and late stage apoptosis in cancer cells, at least in part by activating caspase 3/7-dependent mechanisms. Furthermore, the antitumor efficacy of MSE observed in vitro was also validated in a widely used colon-26 tumor-bearing mouse model. Oral administration of MSE at 50 and 100 mg/kg per day significantly inhibited tumor growth, intratumoral angiogenesis, and liver metastases in BALB/c mice bearing colon-26 tumors (P < 0.05). In conclusion, our findings provide evidence that MSE and GC have potent antitumor activity. Most importantly, we provide the first evidence that MSE inhibits tumor growth, intratumoral angiogenesis, and liver metastasis in a colon-26 tumor-bearing mice.
Volume 4(11)
Pages 1767-80
Published 2015-11
DOI 10.1002/cam4.520
PMID 26408414
PMC PMC4674003
MeSH Animals Antineoplastic Agents, Phytogenic / chemistry Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects Caspases / metabolism Cell Line, Tumor Cell Proliferation / drug effects Colonic Neoplasms / drug therapy Colonic Neoplasms / metabolism Colonic Neoplasms / pathology* Disease Models, Animal Female Gnetum / chemistry* Humans Liver Neoplasms / drug therapy Liver Neoplasms / pathology Liver Neoplasms / secondary Mice Plant Extracts / chemistry Plant Extracts / pharmacology* Seeds / chemistry* Xenograft Model Antitumor Assays
IF 3.357
Times Cited 2
Human and Animal Cells Colon-26(RCB2657)