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Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer

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Abstract

Objective

To investigate the effect of parthenolide on apoptosis and autophagy and to study the role of the PI3K/Akt signaling pathway in cervical cancer.

Results

Parthenolide inhibits HeLa cell viability in a dose dependent-manner and was confirmed by MTT assay. Parthenolide (6 µM) induces mitochondrial-mediated apoptosis and autophagy by activation of caspase-3, upregulation of Bax, Beclin-1, ATG5, ATG3 and down-regulation of Bcl-2 and mTOR. Parthenolide also inhibits PI3K and Akt expression through activation of PTEN expression. Moreover, parthenolide induces generation of reactive oxygen species that leads to the loss of mitochondrial membrane potential.

Conclusion

Parthenolide induces apoptosis and autophagy-mediated growth inhibition in HeLa cells by suppressing the PI3K/Akt signaling pathway and mitochondrial membrane depolarization and ROS generation. Parthenolide may be a potential therapeutic agent for the treatment of cervical cancer.

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Acknowledgments

We sincerely thank Bharathidasan University for providing financial assistance to Mr. Jeyamohan Sridharan through University Research Fellowship (URF). We also thank DST-FIST programme for the instrument facility. The authors are grateful to Dr. Sathees C Ragavan, Indian Institute of Science, Karnataka and Prof. G. Sudhandiran, University of Madras, Tamil Nadu, India for providing the antibodies.

Supporting Information

Supplementary Table 1—Quantitative real-time PCR primers used in this study.

Supplementary Fig. 1—Chromatin condensation and nuclear fragmentation in HeLa cells.

Supplementary Fig. 2—Determination of mitochondrial membrane potential (Δψm).

Supplementary Fig. 3—Parthenolide induced ROS generation in HeLa cells.

Author information

Authors and Affiliations

  1. Molecular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620 024, India

    Sridharan Jeyamohan, Rajesh Kannan Moorthy, Mahesh Kumar Kannan & Antony Joseph Velanganni Arockiam

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  1. Sridharan Jeyamohan
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  2. Rajesh Kannan Moorthy
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  3. Mahesh Kumar Kannan
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  4. Antony Joseph Velanganni Arockiam
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Corresponding author

Correspondence to Antony Joseph Velanganni Arockiam.

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Jeyamohan, S., Moorthy, R.K., Kannan, M.K. et al. Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer. Biotechnol Lett 38, 1251–1260 (2016). https://doi.org/10.1007/s10529-016-2102-7

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  • DOI: https://doi.org/10.1007/s10529-016-2102-7

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