Corosolic acid induces potent anti-cancer effects in CaSki cervical cancer cells through the induction of apoptosis, cell cycle arrest and PI3K/Akt signalling pathway

Authors

  • Yong Qian Xu Department of Gynecology, Qilu Hospital of Shandong university, Jinan 250012
  • Jian Hai Zhang Department of Gynecology, Shengli Oilfield Central Hospital, Dongying 257034
  • Xing Sheng Yang Department of Gynecology, Qilu Hospital of Shandong university, Jinan 250012

DOI:

https://doi.org/10.3329/bjp.v11i2.26793

Keywords:

Anti-cancer, Apoptosis, CaSki cervical cancer cell, Cell cycle arrest, Corosolic acid, PI3K/Akt signalling

Abstract

The main objective of the present study was to investigate the anti-tumor activity of corosolic acid in CaSki human cervical cancer cells. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Results revealed that corosolic acid exerted potent, dose- and time-dependent growth inhibitory effects in CaSki cell proliferation. Cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 µM concentrations of corosolic acid, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Corosolic acid also induced G2/M cell cycle arrest in a dose-dependent manner. Increasing doses of corosolic acid treatment to these cells resulted in significant and dose-dependent down-regulation of PI3K and Akt protein expressions.

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References

Butler MS. Natural products to drugs: Natural product-derived compounds in clinical trials. Nat Prod Rep. 2008; 25: 475516.

Cragg GM, Kingston DGI, Newman DJ (eds). Anti-cancer agents from natural products. Florida, CRC Press/Taylor and Francis, 2005.

Feher M, Schmidt JM. Property distributions: Differences between drugs, natural products and molecules from combinatorial chemistry. J Chem Inf Comput Sci. 2003; 43: 21827.

Fernandes J, Weinlich R, Castilho RO, Kaplan MA, Amarante-Mendes GP, Gattass CR. Pomolic acid triggers mitochondria dependent apoptotic cell death in leukemia cell line. Cancer Lett. 2005; 219: 4955.

Fujiwara Y, Komohara Y, Ikeda T, Takeya M. Corosolic acid inhibits glioblastoma cell proliferation by suppressing the activation of signal transducer and activator of transcription-3 and nuclear factor-kappa B in tumor cells and tumor-associated macrophages. Cancer Sci. 2011; 102: 206-11.

Fujiwara Y, Takaishi K, Nakao J, Ikeda T, Katabuchi H, Takeya M, Komohara Y. Corosolic acid enhances the anti-tumor effects of chemotherapy on epithelial ovarian cancer by inhibiting signal transducer and activator of transcription 3 signaling. Oncol Lett. 2013; 6: 161923.

Horlad H, Fujiwara Y, Takemura K, Ohnishi K, Ikeda T, Tsukamoto H, Mizuta H, Nishimura Y, Takeya M, Komohara Y. Corosolic acid impairs tumor development and lung metastasis by inhibiting the immunosuppressive activity of myeloid-derived suppressor cells. Mol Nutr Food Res. 2013; 57: 1046-54.

Kinghorn AD. Drug discovery from natural products. In: Foyes Principles of medicinal chemistry. Lemke TL, Williams DA (eds). 6th ed. Philadelphia, Wolters Kluwer/Williams and Wilkins, 2008, pp 1225.

Martin R, Carvalho J, Ibeas E, Hernandez M, Ruiz Gutierrez V, Nieto ML. Acidic triterpenes compromise growth and survival of astrocytoma cell lines by regulating reactive oxygen species accumulation. Cancer Res. 2007; 67: 374151.

Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007; 70: 46167.

Page BD, Ball DP, Gunning PT. Signal transducer and activator of transcription 3 inhibitors: A patent review. Expert Opin Ther Pat. 2011; 21: 65-83.

Reyes Zurita FJ, Rufino Palomares EE, Lupianez JA, Cascante M. Maslinic acid, a natural triterpene from Olea europaea L., induces apoptosis in HT29 human colon-cancer cells via the mitochondrial apoptotic pathway. Cancer Lett. 2009; 273: 4454.

Sivakumar G, Vail DR, Nair V, Medina-Bolivar F, Lay JO Jr. Plant-based corosolic acid: Future anti-diabetic drug? Biotechnol J. 2009; 12: 1704-11.

Srivastava V, Negi AS, Kumar JK, Gupta MM, Khanuja SP. Plant-based anti-cancer molecules: A chemical and biological profile of some important leads. Bioorg Med Chem. 2005; 13: 5892-908.

Taraphdar AK, Roy M, Bhattacharya RK. Natural products as inducers of apoptosis: Implication for cancer therapy and prevention. Curr Sci. 2011; 80.

Xin HL, Yue XQ, Xu YF,Wu YC, Zhang YN, Wang YZ, Ling CQ. Two new polyoxygenated triterpenoids from Actinidia valvata. Helv Chim Acta. 2008; 91: 57580.

Published

2016-04-10

How to Cite

Xu, Y. Q., J. H. Zhang, and X. S. Yang. “Corosolic Acid Induces Potent Anti-Cancer Effects in CaSki Cervical Cancer Cells through the Induction of Apoptosis, Cell Cycle Arrest and PI3K/Akt Signalling Pathway”. Bangladesh Journal of Pharmacology, vol. 11, no. 2, Apr. 2016, pp. 453-9, doi:10.3329/bjp.v11i2.26793.

Issue

Section

Research Articles