Zerumbone inhibits prostate cancer cell viability and induces cell death by non-apoptotic pathway

Xian-De Cao, Hui-Min Zheng

Abstract

The aim of the present study was to investigate the role of zerumbone on the proliferation, cell cycle arrest and cell death in DU-145 prostate cancer cell lines. The MTT assay revealed that zerumbone (20 µM) reduced proliferation of DU-145 cells to 39.0% at 48 hours. It also increased the proportion of propidium iodide stained cells to 53.4% compared 1.0% in control. However, the population of annexin V-stained cells remained uneffected indicating induction of non-apoptotic cell death by zerumbone. Treatment of DU-145 cells with zerumbone (20 µM) caused 8-fold enhancement in the level of reactive oxygen species (ROS). On the other hand, exposure of the zerumbone treated DU-145 cells to glutathione inhibited the generation of ROS. Fow cytometry using propidium iodide staining revealed that zerumbone treat-ment increased proportion of cells in G1 phase to 71.3% on compared to 34.7% in the control. The results from Western blot analysis revealed a significant increase in the expression of cyclin D1 protein in DU-145 cells on treatment with 20 µM concentration of zerumbone. Thus, zerumbone treatment inhibits prostate cancer cell viability and can be used for its treatment.

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Keywords

Apoptosis; Prostate cancer cell; Zerumbone

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References

Abbas T, Dutta A. p21 in cancer: Intricate networks and multiple activities. Nat Rev Cancer. 2009; 9: 400-14.

Choi K, Kim J, Kim GW, Choi C. Oxidative stress-induced necrotic cell death via mitochondria-dependent burst of reactive oxygen species. Curr Neurovasc Res. 2009; 6: 213-22.

Di Stefano A, Frosali S, Leonini A, Ettorre A, Priora R, Di Simplicio FC, Di Simplicio P. GSH depletion, protein S-glutathionylation and mitochondrial transmembrane poten-tial hyperpolarization are early events in initiation of cell death induced by a mixture of isothiazolinones in HL60 cells. Biochim Biophys Acta. 2006; 1763: 214-25.

Guo JJ, Li YJ, Xin LL. Tangeretin prevents prostate cancer cell proliferation and induces apoptosis via activation of Notch signalling and regulating the androgen receptor (AR) pathway and the phosphoinositide 3-kinase (PI3k)/Akt/mTOR pathways. Bangladesh J Pharmacol. 2015; 10: 937-47.

Gupta SC, Kim JH, Prasad S, et al. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev. 2010; 29: 405-34.

Hood JE, Jenkins JW, Milatovic D, Rongzhu L, Aschner M. Mefloquine induces oxidative stress and neurodegeneration in primary rat cortical neurons. Neurotoxicology 2010; 31: 518-23.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010; 60: 277-300.

Kim M, Miyamoto S, Yasui Y, Oyama T, Murakami A, Tanaka T. Zerumbone, a tropical ginger sesquiterpene, inhibits colon and lung carcinogenesis in mice. Int J Cancer. 2009; 124: 264-71.

Kirana C, McIntosh GH, Record IR, Jones GP. Antitumor activity of extract of Zingiber aromaticum and its bioactive sesquiterpenoid zerumbone. Nutr Cancer. 2003; 45: 218-25.

Lin E, Zhang X, Wang D, Hong S, Li L. Naringenin modulates the metastasis of human prostate cancer cells by down- regulating the matrix metalloproteinases -2/-9 via ROS/ERK1/2 pathways. Bangladesh J Pharmacol. 2014; 9: 419-27.

Murakami A, Takahashi D, Kinoshita T, et al. Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, pro-inflammatory protein produc-tion, and cancer cell proliferation accompanied by apoptosis: The alpha, beta-unsaturated carbonyl group is a prerequisite. Carcinogenesis 2002; 23: 795-802.

Sung B, Jhurani S, Ahn KS, et al. Zerumbone down-regulates chemokine receptor CXCR4 expression leading to inhibition of CXCL12-induced invasion of breast and pancreatic tumor cells. Cancer Res. 2008; 68: 8938-44.

Sung B, Murakami A, Oyajobi BO, Aggarwal BB. Zerumbone abolishes RANKL-induced NF-?B activation, inhibits osteo-clastogenesis, and suppresses human breast cancer-induced bone loss in athymic nude mice. Cancer Res. 2009; 69: 1477-84.

Takada Y, Murakami A, Aggarwal BB. Zerumbone abolishes NF-?B and I?B? kinase activation leading to suppression of antiapoptotic and metastatic gene expression, up-regulation of apoptosis, and down-regulation of invasion. Oncogene 2005; 24: 6957-69.

Xian M, Ito K, Nakazato T, 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.

Yodkeeree S, Sung B, Limtrakul P, Aggarwal BB. Zerumbone enhances TRAIL-induced apoptosis through the induction of death receptors in human colon cancer cells: Evidence for an essential role of reactive oxygen species. Cancer Res. 2009; 69: 6581-89.

Yob NJ, Jofrry SM, Affandi MM, et al. Zingiber zerumbet (L.) Smith: A review of its ethnomedicinal, chemical, and pharmacological uses. Evid Based Complement Alternat Med. 2011: 543216.



DOI: http://dx.doi.org/10.3329/bjp.v11i4.26728

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Bangladesh Journal of Pharmacology (Bangladesh J Pharmacol) is a single-blinded peer-reviewed, video component, open access official publication of the Bangladesh Pharmacological Society (BDPS). eISSN: 1991-0088. For contact: Editor-In-Chief