ZERUMBONE (ZER) INDUCES APOPTOSIS IN HEPG2 CELLS VIA MITOCHONDRIAL PATHWAY

Authors

  • Nozlena A. Samad university putra malaysia
  • Ahmad Bustamam Abdul Universiti Putra Malaysia
  • Rasedee Abdullah Universiti Putra Malaysia
  • Tengku Azmi Tengku Ibrahim Universiti Putra Malaysia
  • Heshu Rahman Universiti Putra Malaysia
  • Yeap Swee Keong Universiti Putra Malaysia

Keywords:

Zerumbone, HepG2, Apoptosis, Caspase-3, Caspase-9

Abstract

Objective: The aim of the study is to determine the anti-cancer effect of ZER on the human hepatocellular carcinoma (HepG2) cell line.

Methods: The anti-cancer mechanisms investigated were apoptosis and anti-proliferation. The assays used in the in vitro study were 3-4-5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT), annexin V and acridine orange/propidium iodide staining, and cell cycle analysis to determine apoptosis. Colorimetric assays were employed for caspase-3 and 9 determinations. The morphological changes were determined by scanning electron microscopy.

Results: Zerumbone inhibited the proliferation of HepG2 cells in a dose-dependent manner and induced cell cycle arrest at the G2/M phase and apoptosis, shown by chromatin condensation, cell shrinkage and formation of apoptotic bodies, in the HepG2 cells in a time-dependent manner. Zerumbone also stimulated caspase-3 and-9 activities in the HepG2 cells.

Conclusions: This study suggests that the induction of apoptosis of ZER on HepG2 was via the mitochondrial pathway.

 

Downloads

Download data is not yet available.

References

McGlynn KA, Tsao L, Hsing AW, Devesa SS, Fraumeni JF. International trends and patterns of primary liver cancer. Int J Cancer 2001;94:290–6.

Ananthakrishnan A, Gogineni V, Saeian K. Epidemiology of primary and secondary liver cancers. Semin Intervent Radiol 2006;23:47–63.

Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000;64:51–68.

Perz JF, Armstrong GL, Farrington LA, Hutin YJF, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529–38.

Constantin CV, Streba CT, Rogoveanu I, Nita-Stefanescu L, Ionescu AG. Cirrhosis and chronic viral hepatitis as risk factors for hepatocellular carcinoma: romanian single-clinic experience. Med 2010;5:265–70.

Kumar PS, Febriyanti RM, Sofyan FF, Luftimas DE, Abdulah R. Anticancer potential of Syzygium aromaticum L. in MCF-7 human breast cancer cell lines. Pharmacogn Res 2014;6:350–4.

Noor Rain A, Khozirah S, Mohd Ridzuan MAR, Ong BK, Rohaya C, Rosilawati M, et al. Antiplasmodial properties of some malaysian medicinal plants. Trop Biomed 2007;24:29–35.

Yob NJ, Jofrry SM, Affandi MMRMM, Teh LK, Salleh MZ, Zakaria ZA. Zingiber zerumbet (L.) Smith: A Review of Its Ethnomedicinal, Chemical, and Pharmacological Uses. Evidence-Based Complementary Altern Med 2011;2011:543216.

Kitayama T, Okamoto T, Hill RK, Kawai Y, Takahashi S, Yonemori S, et al. Chemistry of Zerumbone. 1. Simplified Isolation, Conjugate Addition Reactions, and a unique ring contracting transannular reaction of its dibromide. J Org Chem 1999;64:2667–72.

Zakaria ZA, Mohamad AS, Chear CT, Wong YY, Israf DA, Sulaiman MR. Antiinflammatory and antinociceptive activities of Zingiber zerumbet methanol extract in experimental model systems. Med Princ Pract 2010;19:287–94.

Rahman HS, Rasedee A, Abdul AB, Zeenathul NA, Othman HH, Yeap SK, et al. Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line. Int J Nanomed 2014;9:527–38.

Abdelwahab SI, Abdul AB, Zain ZNM and Hadi AHA. Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells. Int Immunopharmacol 2012;12:594–602.

Sakinah SAS, Handayani ST, Hawariah LPA. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio. Cancer Cell Int 2007;7:4.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.

Alshatwi AA. Catechin hydrate suppresses MCF-7 proliferation through TP53/Caspase-mediated apoptosis. J Exp Clin Cancer Res 2010;29:167.

Lucas DM, Still PC, Pérez LB, Grever MR, Kinghorn AD. Potential of plant-derived natural products in the treatment of leukemia and lymphoma. Curr Drug Targets 2010;11:812–22.

O’Brien MA, Kirby R. Apoptosis: A review of pro-apoptotic and anti-apoptotic pathways and dysregulation in disease. J Veterinary Emergency Critical Care 2008;18:572–85.

Cooper GM. The Development and Causes of Cancer. Sinauer Associates; 2000.

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Intracellular Control of Cell-Cycle Events. Garland Science; 2002.

Xian M, Ito K, Nakazato T, Shimizu T, Chen CK, Yamato K, et al. Zerumbone, a bioactive sesquiterpene, induces G2/M cell cycle arrest and apoptosis in leukemia cells via a Fas-and mitochondria-mediated pathway. Cancer Sci 2007;98:118–26.

Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods 1995;184:39–51.

Gerl R, Vaux DL. Apoptosis in the development and treatment of cancer.†Carcinogenesis 2005;26:263–70.

McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb. Perspect Biol 2013;5:a008656.

Lavrik IN, Golks A, Krammer PH. Caspases: pharmacological manipulation of cell death. J Clin Invest 2005;115(10):2665–72.

Published

01-05-2015

How to Cite

Samad, N. A., A. B. Abdul, R. Abdullah, T. A. T. Ibrahim, H. Rahman, and Y. S. Keong. “ZERUMBONE (ZER) INDUCES APOPTOSIS IN HEPG2 CELLS VIA MITOCHONDRIAL PATHWAY”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 5, May 2015, pp. 298-02, https://journals.innovareacademics.in/index.php/ijpps/article/view/4399.

Issue

Section

Original Article(s)