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

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.

Gnetin‐C and other resveratrol oligomers with cancer chemopreventive potential

“…MSE and gnetin‐C induced apoptosis in all tested tumor cells but were not toxic to nonmalignant cells. In the same study, the oral administration of MSE significantly inhibited tumor growth, intratumoral angiogenesis, and the development of liver metastases in mice bearing colon‐26 tumors …”

Analysis of Compounds Isolated from Gnetum gnemon L. Seeds as Potential ACE Inhibitors through Molecular Docking and Molecular Dynamics Simulations

“…Melinjo is widely available and consumed in large quantities in Indonesia. 1 Hydrolyzed-proteins of melinjo seed had been proven to lower blood pressure of hypertensive rats.…”

Melinjo (Gnetum gnemon) Seed Extract Consumption during Lactation Improved Vasodilation and Attenuated the Development of Hypertension in Female Offspring of Fructose‐Fed Pregnant Rats

“…Melinjo seeds are part of the Indonesian cuisine due to their high nutritive value. In fact, melinjo seed extracts are also now sold in Japan as nutritional supplement (Narayanan et al, ). Plants in this family are used in folkloric treatments for diabetes, arthritis, and bronchitis (Ota et al, ).…”

“…Plants in this family are used in folkloric treatments for diabetes, arthritis, and bronchitis (Ota et al, ). It was reported that oral administration of melinjo seed extracts does not produce significant adverse effects to laboratory animals or humans (Narayanan et al, ) and oral administration of 1000 mg/kg per day of melinjo seed extracts in rats had no observed adverse effect level (Tatefuji et al, ). Resveratrol extracted from melinjo seeds was reported to have antiangiogenic effects; inhibitory effects against endothelial senescence, tyrosinase activity, and melanin biosynthesis; and cancer preventive effects (Kunimasa et al, ; Yanagihara et al, ; Ota et al, ).…”