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Deoxyelephantopin impairs growth of cervical carcinoma SiHa cells and induces apoptosis by targeting multiple molecular signaling pathways

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Abstract

Deoxyelephantopin, a sesquiterpene lactone extracted and purified from Elephantopus scaber, has been shown to exhibit antitumor and hepatoprotective activities. The purpose of this study was to investigate the antiproliferative and apoptosis-inducing properties of deoxyelephantopin in SiHa cells and to elucidate the underlying molecular mechanisms. Deoxyelephantopin inhibited growth of SiHa cells and triggered apoptosis. Apoptosis was accompanied by sequential activation of caspases (8, 9, 3, and 7) and reactive oxygen species (ROS) production. Downregulation of antiapoptotic proteins (Bcl2 and Bcl-xL) and upregulation of apoptotic protein (bax) were also detected. Our results demonstrated that deoxyelephantopin-induced G2/M phase arrest was associated with a marked increase in the levels of p53 and p21 and a decrease in phospho-signal transducer and activator of transcription 3 (pSTAT3-Tyr705), cyclin-dependent kinase 1 (cdc2), and cyclin B1. The expression of p-Akt and p-mTOR was downregulated. p-ERK was inhibited while p-JNK and p-p38 was activated on deoxyelephantopin treatment. Our findings provided the first evidence that STAT3/p53/p21 signaling, MAPK pathway, PI3k/Akt/mTOR pathway, caspase cascades, and ROS play critical roles in deoxyelephantopin-induced G2/M phase arrest and apoptosis of SiHa cells.

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Acknowledgments

The first author would like to express gratitude to University Grant Commission (UGC) for financial support. This research work was supported by Indian Council for Medical Research, New Delhi, India (grant no. 59/47/2011/BMS/TRM).'

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

    Arakkaveettil Kabeer Farha & Prathapan Remani

  2. CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India

    Sethumadhavannair Rajalekshmi Dhanya & Sivasankaran Nair Mangalam

  3. Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Thiruvananthapuram, India

    Balakrishnan Sreedevi Geetha & Panickamparambil Gopalakrishnan Latha

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  1. Arakkaveettil Kabeer Farha
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  2. Sethumadhavannair Rajalekshmi Dhanya
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  3. Sivasankaran Nair Mangalam
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  4. Balakrishnan Sreedevi Geetha
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Correspondence to Prathapan Remani.

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Farha, A.K., Dhanya, S.R., Mangalam, S.N. et al. Deoxyelephantopin impairs growth of cervical carcinoma SiHa cells and induces apoptosis by targeting multiple molecular signaling pathways. Cell Biol Toxicol 30, 331–343 (2014). https://doi.org/10.1007/s10565-014-9288-z

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  • DOI: https://doi.org/10.1007/s10565-014-9288-z

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