Abstract

Abstract Over the passed decade, advances in understanding carcinogenesis have made possible the identification of the candidates of chemopreventive agents to be developed in targeting the key molecules. Lotus (Nelumbo nucifera Gaertn) is widely distributed in central and southern Taiwan. Its leaves are becoming popular as an ingredient of healthy beverages. Nelumbo nucifera Leaf extract (NLE) has been reported to exhibit different therapeutic effects, such as anti-oxidant and reduction of risks for cardiovascular disease. This study was aimed to investigate the antitumor effect of NLE on human MCF-7 cell line in vitro and in vivo. Qualitative analysis showed that the NLE contains several compounds using nine kinds of standard polyphenols by high-performance liquid chromatography (HPLC) method. The polyphenols present in identified compound of NLE were mainly gallic acid, rutin and quercetin. The MTT data showed no significant inhibition on growth of MCF-7 cells following NLE treatment, whereas flow cytometry revealed that the cell cycle was arrested at G0/G1 phase with a dose of 3 mg/ml in MCF-7 cells (approximately 86.54%). With western blotting, we found that treatment with NLE particularly induced p53 phosphorylation and p21 expression, and down-regulated expression of cyclins (cyclin D, cyclin E) and cyclin-dependent kinases (cdk2, cdk4) in a dose-dependent manner. The increased p21 also correlated with the decrease of cyclin D/cdk4 and cyclin E/cdk2 complexes, which was responsible for the high protein expression of Rb/E2F. Inactivation of fatty acid synthase (FAS) was shown in vitro and in vivo, implying that FAS was a potent regulator as well of NLE- mediated anti-carcinogenesis. The tumoricidal effect of NLE was further measured using a xenograft nude mice model. Treatment with NLE (0.5 and 1%) effectively reduced the tumor volume and tumor weight in the nude mice inoculated with MCF-7 cells when compared to the control tissue samples. These results confirmed that cell cycle arrest is sufficient to elicit tumor regression after NLE treatment. In conclusion, our studies indicate that NLE offers an anti-tumor activity and potentially can act as a chemotherapeutic agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2485.

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