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.
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.
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DOI：
10.1002/cam4.520
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发表时间：
2015-11
期刊：
影响因子：
4
通讯作者：
Narayanan B
中科院分区：
文献类型：
--
作者：
Narayanan NK;Kunimasa K;Yamori Y;Mori M;Mori H;Nakamura K;Miller G;Manne U;Tiwari AK;Narayanan B
[医]买麻藤（Gnetum gnemon L.）种子提取物（MSE）及其活性成分买麻藤素C（GC）（白藜芦醇二聚体）已被证明具有广谱的药理活性。在这项研究中，我们研究了MSE和GC的抗肿瘤活性，使用人类和小鼠肿瘤细胞培养模型在体外。GC的抗肿瘤活性与反式白藜芦醇（tRV），芪类多酚。我们的研究结果表明，MSE和GC在临床可达到的浓度显着抑制胰腺癌，前列腺癌，乳腺癌和结肠癌细胞类型的增殖（P < 0.05），而不影响正常细胞。GC的抗肿瘤活性显著高于tRV（P < 0.05）。MSE和GC均能显著诱导肿瘤细胞凋亡，表明MSE和GC通过诱导凋亡抑制肿瘤细胞生长（P < 0.001）。我们的研究结果提供了证据，MSE可能通过caspase-3/7依赖和非依赖的机制诱导癌细胞凋亡。然而，GC可能触发癌细胞的早期和晚期凋亡，至少部分通过激活caspase 3/7依赖性机制。此外，在体外观察到的MSE的抗肿瘤功效也在广泛使用的结肠-26荷瘤小鼠模型中得到验证。每天口服50和100 mg/kg的MSE可显著抑制荷结肠癌BALB/c小鼠的肿瘤生长、瘤内血管生成和肝转移（P < 0.05）。总之，我们的研究结果提供了证据，MSE和GC具有强大的抗肿瘤活性。最重要的是，我们提供了第一个证据表明，MSE抑制肿瘤生长，肿瘤内血管生成，并在结肠-26荷瘤小鼠肝转移。
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.