Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/97553
Title: NF-κB p65 repression by the sesquiterpene lactone, Helenalin, contributes to the induction of autophagy cell death
Authors: Feng, XiaoLing
Zhao, Yan
Lim, Chuan Bian
Fu, Pan You
Ky, Nung
Zhu, Hong Shuang
Li, Jinming
Srinivasan, Kandhadayar Gopalan
Hamza, Mohamed Sabry
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Lim, C. B., Fu, P. Y., Ky, N., Zhu, H. S., Feng, X., Li, J., et al. (2012). NF-κB p65 repression by the sesquiterpene lactone, Helenalin, contributes to the induction of autophagy cell death. BMC Complementary and Alternative Medicine, 12(1), 93-.
Series/Report no.: BMC complementary and alternative medicine
Abstract: Background. Numerous studies have demonstrated that autophagy plays a vital role in maintaining cellular homeostasis. Interestingly, several anticancer agents were found to exert their anticancer effects by triggering autophagy. Emerging data suggest that autophagy represents a novel mechanism that can be exploited for therapeutic benefit. Pharmacologically active natural compounds such as those from marine, terrestrial plants and animals represent a promising resource for novel anticancer drugs. There are several prominent examples from the past proving the success of natural products and derivatives exhibiting anticancer activity. Helenalin, a sesquiterpene lactone has been demonstrated to have potent anti-inflammatory and antitumor activity. Albeit previous studies demonstrating helenalin’s multi modal action on cellular proliferative and apoptosis, the mechanisms underlying its action are largely unexplained. Methods. To deduce the mechanistic action of helenalin, cancer cells were treated with the drug at various concentrations and time intervals. Using western blot, FACS analysis, overexpression and knockdown studies, cellular signaling pathways were interrogated focusing on apoptosis and autophagy markers. Results. We show here that helenalin induces sub-G1 arrest, apoptosis, caspase cleavage and increases the levels of the autophagic markers. Suppression of caspase cleavage by the pan caspase inhibitor, Z-VAD-fmk, suppressed induction of LC3-B and Atg12 and reduced autophagic cell death, indicating caspase activity was essential for autophagic cell death induced by helenalin. Additionally, helenalin suppressed NF-κB p65 expression in a dose and time dependent manner. Exogenous overexpression of p65 was accompanied by reduced levels of cell death whereas siRNA mediated suppression led to augmented levels of caspase cleavage, autophagic cell death markers and increased cell death. Conclusions. Taken together, these results show that helenalin mediated autophagic cell death entails inhibition of NF-κB p65, thus providing a promising approach for the treatment of cancers with aberrant activation of the NF-κB pathway.
URI: https://hdl.handle.net/10356/97553
http://hdl.handle.net/10220/10581
ISSN: 1472-6882
DOI: 10.1186/1472-6882-12-93
Schools: School of Biological Sciences 
Rights: © 2012 The Author(s). This paper was published in BMC Complementary and Alternative Medicine and is made available as an electronic reprint (preprint) with permission of The Author(s). The paper can be found at the following official DOI: [http://dx.doi.org/10.1186/1472-6882-12-93]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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