Open Access Research article

NF-κB p65 repression by the sesquiterpene lactone, Helenalin, contributes to the induction of autophagy cell death

Chuan Bian Lim1, Pan You Fu3, Nung Ky1, Hong Shuang Zhu1, XiaoLing Feng2, Jinming Li1, Kandhadayar Gopalan Srinivasan4, Mohamed Sabry Hamza5* and Yan Zhao1*

Author Affiliations

1 Division of Chemical Biology and Biotechnology, School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore

2 HeiLongJiang University of Chinese Medicine, Harbin, People’s Republic of China

3 National Cancer Centre of Singapore, NCCS-VARI Translational Research Laboratory, #501, Level 5, 11 Hospital Drive, Singapore 169610, Singapore

4 1stBASE Pte Ltd., 41 Singapore Science Park II, The Gemini, Singapore 117610, Singapore

5 MSD, Translational Medicine Research Center, 8 Biomedical Grove, #04-01/-05 & #05-01/05, Neuros Building, Singapore 138665, Singapore

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BMC Complementary and Alternative Medicine 2012, 12:93  doi:10.1186/1472-6882-12-93

Published: 11 July 2012



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.


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.


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.


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.

Helenalin or Hele(Helenalin); Autophagy; Caspase; NF-κB; Atg12 and LC3-B