Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth
| Autor: | Cui Shen, Ying-jun Zhou, MeiChen Zhou, GuangYao Zeng, Y. Eric Shi, Weiping Pu, Louis Potters, Yiding Chen, JianGuo Cao, Yan-lan Li, Yiliang Ellie Liu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research Programmed cell death Poly ADP ribose polymerase Vitexin Mice Nude Apoptosis Models Biological Lignans Article Rats Sprague-Dawley chemistry.chemical_compound Mice Neoplasms Tumor Cells Cultured Animals Humans Apigenin Caspase Cell Proliferation Lignan Flavonoids biology Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Secoisolariciresinol diglucoside Rats Tumor Burden Oncology chemistry Biochemistry Cancer cell Cancer research biology.protein Female HeLa Cells |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 15(16) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: Lignans such as secoisolariciresinol diglucoside in flaxseed, are metabolizes to bioactive mammalian lignans of END and ENL. Because mammalian lignans have chemical structural similarity to the natural estrogen, they are thought to behave like selective estrogen receptor modulators and therefore have anticancer effect against hormone-related cancers. We isolated a series of lignan compounds, named as Vitexins, from the seed of Chinese herb Vitex Negundo. Experimental Design: We purified several Vitexin lignan compounds. Cytotoxic and antitumor effects were analyzed in cancer cells and in tumor xenograft models. In vivo metabolism of Vitexins was determined in rat. Results: Contrasts to the classic lignans, Vitexins were not metabolized to END and ENL. A mixture of Vitexins EVn-50 and purified Vitexin compound 6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-3, 4-dihydro-2-naphthaldehyde have cytotoxic effect on breast, prostate, and ovarian cancer cells and induces apoptosis with cleavage in poly ADP ribose polymerase protein, up-regulation of Bax, and down-regulation of Bcl-2. This induction of apoptosis seems to be mediated by activation of caspases because inhibition of caspases activity significantly reduced induced apoptosis. We showed a broad antitumor activity of EVn-50 on seven tumor xenograft models including breast, prostate, liver, and cervical cancers. Consistent with in vitro data, EVn-50 treatment induced apoptosis, down-regulated of Bcl-2, and up-regulated Bax in tumor xenografts. Conclusion: Vitexin is a class of nature lignan compounds, whose action and anticancer effect is mediated by the mechanisms different from the classic lignans. Vitexin-induced antitumor effect and cytotoxic activity is exerted through proapoptotic process, which is mediated by a decreased Bcl-2/Bax ratio and activation of caspases. (Clin Cancer Res 2009;15(16):5161–9) |
| Databáze: | OpenAIRE |
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