All Title Author
Keywords Abstract

ROS-Dependent Cell Death Induced by Parthenolide in Human Hepatoma Cell HepG2

DOI: 10.4236/oalib.1106025, PP. 1-18

Subject Areas: Molecular Biology

Keywords: Parthenolide, ROS, Cell Death

Full-Text   Cite this paper   Add to My Lib


With the increase of the action time and dosing concentration, the proliferation of HepG2 cell was inhibited and its vitality gradually decreased. FCM showed that, with the increase of PN action time, the MMP gradually decreased; calcium ions flowed inwards; the cell cycle was arrested in phase G1; the cell apoptosis rate, especially late apoptosis and necrotic cells, increased. The shear expression of apoptosis-related proteins caspase3 and caspase9 was up-regulated; the shear expression of AIF, MIF and PARP1 proteins associated with Caspase-independent apoptosis, i.e. Parthanatos apoptosis, showed time-dependent up-regulation; the long and short expressions of anti-apoptosis protein FLIP showed different degrees of decrease; the ex-pression of autophagy-related proteins LC3A/B and becin-1 was up-regulated; the expression of P62 protein was down-regulated; the expression of cycle- related proteins P53, P27 and P21 increased significantly; the expression of CyclinD1 and CyclinE1 decreased. FCM was used to detect the increase of ROS with the action time of PN; and its generation level showed an increasing trend; after the combination with ROS scavenger NAC, there was no significant difference in cell viability with the control group. There was no significant difference in the expression level of relevant cell death protein with DMSO control group. There was no difference in intracellular ROS generation level with the control group. Conclusion: PN induces the ROS generation in HepG2 cell, blocks its cycle and causes apoptosis and au-tophagy to play an anti-tumor effect.

Cite this paper

Xu, W. , Ge, K. , Guo, Y. , Zhu, W. , Liu, L. and Zhou, Y. (2020). ROS-Dependent Cell Death Induced by Parthenolide in Human Hepatoma Cell HepG2. Open Access Library Journal, 7, e6025. doi:


[1]  Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424.
[2]  Mcglynn, K.A., Petrick, J.L. and London, W.T. (2015) Global Epidemiology of Hepatocellular Carcinoma. Clinics in Liver Disease, 19, 223-238.
[3]  Lafaro, K.J., Demirjian, A.N. and Pawlik, T.M. (2015) Epidemiology of Hepatocellular Carcinoma. Surgical Oncology Clinics of North America, 24, 1-17.
[4]  Knight, D.W. (1995) Feverfew: Chemistry and Biological Activity. Natural Product Reports, 12, 271.
[5]  Benassi-Zanqueta, é., Marques, C.F., Nocchi, S.R., Dias Filho, B.P., Nakamura, C.V. and Ueda-Nakamura, T. (2018) Par-thenolide Influences Herpes Simplex Virus 1 Replication in Vitro. Intervirology, 61, 14-22.
[6]  López-Franco, O., Hernán-dez-Vargas, P., Ortiz-Mu?oz, G., Sanjuán, G., Suzuki, Y., Ortega, L., et al. (2006) Par-thenolide Modulates the NF-κB-Mediated Inflammatory Responses in Experimental Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 26, 1864-1870.
[7]  Suzuki, T., Saitoh, Y., Isozaki, S. and Ishida, R. (1973) Simple Method for Portal Vein Infusion in the Rat. Journal of Pharmaceutical Sciences, 62, 345-347.
[8]  Zhang, S., Lin, Z.N., Yang, C.F., Shi, X., Ong, C.N. and Shen, H.M. (2004) Suppressed NF-kappaB and Sustained JNK Activation Contribute to the Sensitization Effect of Parthenolide to TNF-Alpha-Induced Apoptosis in Human Cancer Cells. Carcinogenesis, 25, 2191-2199.
[9]  Gopal, Y.N., Arora, T.S. and Van Dyke, M.W. (2007) Parthenolide Specifically Depletes Histone Deacetylase 1 Protein and Induces Cell Death through Ataxia Telangiectasia Mutated. Chemistry & Biology, 14, 813-823.
[10]  Liu, Z., Liu, S., Xie, Z., Pavlovicz, R.E., Wu, J., Chen, P., et al. (2009) Modulation of DNA Methylation by a Sesquiterpene Lactone Parthenolide. Journal of Pharmacology and Experimental Therapeutics, 329, 505-514.
[11]  Wen, J., You, K.R., Lee, S.Y., Song, C.H. and Kim, D.G. (2002) Oxidative Stress- Mediated Apoptosis. The Anticancer Effect of the Sesquiterpene Lactone Parthenolide. The Journal of Biological Chemistry, 277, 38954-38964.
[12]  Li, H., Lu, H., Lv, M., Wang, Q. and Sun, Y. (2018) Parthenolide Facilitates Apoptosis and Reverses Drug-Resistance of Human Gastric Carcinoma Cells by Inhibiting the STAT3 Signaling Pathway. Oncology Letters, 15, 3572-3579.
[13]  Kroemer, G., Dallaporta, B. and Resche-Rigon, M. (1998) The Mitochondrial Death/ Life Regulator in Apoptosis and Necrosis. Annual Review of Physiology, 60, 619-642.
[14]  Ermak, G. and Davies, K.J.A. (2002) Calcium and Oxidative Stress: From Cell Signaling to Cell Death. Molecular Immunology, 38, 713-721.
[15]  Sherr, C.J. (1996) Cancer Cell Cycles. Science, 274, 1672-1677.
[16]  Hengartner, M.O. (2000) The Biochemistry of Apoptosis. Nature, 407, 770-776.
[17]  Yun, C. and Lee, S. (2018) The Roles of Autophagy in Cancer. International Journal of Molecular Sciences, 19, 3466.
[18]  Mathema, V.B., Koh, Y., Thakuri, B.C. and Sillanp??, M. (2012) Parthenolide, a Sesquiterpene Lactone, Expresses Multiple Anti-Cancer and Anti-Inflammatory Activities. Inflammation, 35, 560-565.
[19]  Tollini, L.A., Jin, A., Park, J. and Zhang, Y. (2014) Regulation of p53 by Mdm2 E3 Ligase Function Is Dispensable in Embryogenesis and Development, But Essential in Response to DNA Damage. Cancer Cell, 26, 235-247.
[20]  Gartel, A.L. and Tyner, A.L. (2002) The Role of the Cyclin-Dependent Kinase Inhibitor p21 in Apoptosis. Molecular Cancer Therapeutics, 1, 639-649.
[21]  Abbastabar, M., Kheyrollah, M., Azizian, K., Bagherlou, N., Tehrani, S.S., Maniati, M., et al. (2018) Multiple Functions of p27 in Cell Cycle, Apoptosis, Epigenetic Modification and Transcriptional Regulation for the Control of Cell Growth: A Double-Edged Sword Protein. DNA Repair, 69, 63-72.
[22]  Fatokun, A.A., Dawson, V.L. and Dawson, T.M. (2014) Parthanatos: Mitochondrial-Linked Mechanisms and Therapeutic Opportunities. British Journal of Pharmacology, 171, 2000-2016.
[23]  Ravanan, P., Srikumar, I.F. and Talwar, P. (2017) Autophagy: The Spotlight for Cellular Stress Responses. Life Sciences, 188, 53-67.
[24]  Vakifahmetoglu-Norberg, H., Ouchida, A.T. and Norberg, E. (2017) The Role of Mitochondria in Metabolism and Cell Death. Biochemical and Biophysical Research Communications, 482, 426-431.
[25]  Mailloux, R.J. (2018) Mitochondrial Antioxidants and the Maintenance of Cellular Hydrogen Peroxide Levels. Oxidative Medicine and Cellular Longevity, 2018, Article ID: 7857251.
[26]  Ghantous, A., Sinjab, A., Herceg, Z. and Darwiche, N. (2013) Parthenolide: From Plant Shoots to Cancer Roots. Drug Discovery Today, 18, 894-905.
[27]  Duan, D., Zhang, J., Yao, J., Liu, Y. and Fang, J. (2016) Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells. Journal of Biological Chemistry, 291, 10021-10031.


comments powered by Disqus

Contact Us


微信:OALib Journal