Cucurbitacin L 2-O-β-Glucoside demonstrates apoptogenesis in colon adenocarcinoma cells (HT-29): involvement of reactive oxygen and nitrogen species regulation

Abdelwahab, S.I.; Hassan, L.E.; Abdul Majid, A.M.; Yagi, S.M.; Mohan, S.; Elhassan Taha, M.M.; Ahmad, S.; Chuen, C.S.; Narrima, P.; Rais, M.M.; Syam, S.; Moharam, B.A.; Hadi, A.H. (2012) Cucurbitacin L 2-O-β-Glucoside demonstrates apoptogenesis in colon adenocarcinoma cells (HT-29): involvement of reactive oxygen and nitrogen species regulation. Evidence-Based Complementary and Alternative Medicine. ISSN 1741-427X

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    Abstract

    Emerging evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species can contribute to diverse signalling pathways of inflammatory and tumour cells. Cucurbitacins are a group of highly oxygenated triterpenes. Many plants used in folk medicine to treat cancer have been found to contain cucurbitacins displaying potentially important anti-inflammatory actions. The current study was designed to investigate the anti-ROS and -RNS effects of cucurbitacin L 2-O-β-glucoside (CLG) and the role of these signaling factors in the apoptogenic effects of CLG on human colon cancer cells (HT-29). This natural cucurbitacin was isolated purely from Citrullus lanatus var. citroides (Cucurbitaceae). The results revealed that CLG was cytotoxic to HT-29. CLG increased significantly (P < 0.05) RNA and protein levels of caspase-3 in HT-29 cells when verified using a colorimetric assay and realtime qPCR, respectively. The results showed that lipopolysaccharide/interferon-gamma (LPS/INF-γ) increased nitrous oxide (NO) production inR AW264.7macrophages, whereas N(G)-nitro-L-argininemethyl ester (L-NAME) and CLG curtailed it. This compound did not reveal any cytotoxicity on RAW264.7 macrophages and human normal liver cells (WRL-68) when tested using the MTT assay. Findings of ferric reducing antioxidant power (FRAP) and oxygen radical absorption capacity (ORAC) assays demonstrate the antioxidant properties of CLG. The apoptogenic property of CLG on HT-29 cells is thus related to inhibition of reactive nitrogen and oxygen reactive species and the triggering of caspase-3-regulated apoptosis.

    Item Type: Article
    Journal or Publication Title: Evidence-Based Complementary and Alternative Medicine
    Additional Information: Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
    Uncontrolled Keywords: Pharmacy
    Subjects: R Medicine > RS Pharmacy and materia medica
    Divisions: Faculty of Medicine
    Depositing User: Mr. Faizal Hamzah
    Date Deposited: 15 Jun 2012 09:19
    Last Modified: 27 Sep 2013 10:41
    URI: http://eprints.um.edu.my/id/eprint/3309

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