Subscribe to RSS
DOI: 10.1055/s-0042-107083
Cytotoxic and Antitumor Effects of Curzerene from Curcuma longa
Publication History
received 05 November 2015
revised 07 April 2016
accepted 15 April 2016
Publication Date:
10 June 2016 (online)
Abstract
Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine Curcuma rhizomes. In this study, anticancer activity of curzerene was examined in both in vitro and in vivo models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC50s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects in vivo. In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both in vitro and in vivo models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.
* These authors contributed equally to this work.
-
References
- 1 Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9-29
- 2 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-2917
- 3 He J, Zhao P, Chen WQ. Chinese cancer registry annual report 2012. Beijing: Press of Military Medical Sciences; 2012: 13-16
- 4 Jeong SJ, Koh W, Kim B, Kim SH. Are there new therapeutic options for treating lung cancer based on herbal medicines and their metabolites?. J Ethnopharmacol 2011; 138: 652-661
- 5 Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann N Y Acad Sci 2005; 1056: 206-217
- 6 Pescosolido N, Giannotti R, Plateroti AM, Pascarella A, Nebbioso M. Curcumin: therapeutical potential in ophthalmology. Planta Med 2014; 80: 249-254
- 7 Zhang X, Zhang Y, Li Y. β-Elemene decreases cell invasion by upregulating E-cadherin expression in MCF-7 human breast cancer cells. Oncol Rep 2013; 30: 745-750
- 8 Mao Y, Zhang J, Hou L, Cui X. The effect of beta-elemene on alpha-tubulin polymerization in human hepatoma HepG2 cells. Chin J Cancer Res 2013; 25: 770-776
- 9 Shaoping L. One kind of Curcuma oil extract and its preparation method and pharmaceutical compositions containing it. Chinese Patent CN1557387, 2004
- 10 Zeng J, Huang F, Liao Y. New progress of content determination methods ant anti-tumor effect of zedoary oil. Anti-tumor Pharmacy 2012; 02: 19-22
- 11 Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005; 45: 51-88
- 12 Khan MS, Khan MK, Siddiqui MH, Arif JM. An in vivo and in silico approach to elucidate the tocotrienol-mediated fortifiation against infection and inflammation induced alterations in antioxidant defense system. Eur Rev Med Pharmacol Sci 2011; 15: 916-930
- 13 Holley SL, Fryer AA, Haycock JW, Grubb SE, Strange RC, Hoban PR. Differential effects of glutathione S-transferase pi (GSTP1) haplotypes on cell proliferation and apoptosis. Carcinogenesis 2007; 28: 2268-2273
- 14 Zang L, Shi L, Guo J, Pan Q, Wu W, Pan X, Wang J. Screening and identification of a peptide specifically targeted to NCI-H1299 from a phage display peptide library. Cancer Lett 2009; 281: 64-70
- 15 Pan XD, Yang ZP, Tang QL, Peng T, Zhang ZB, Zhou SG, Wang GX, He B, Zang LQ. Expression and function of GSTA1 in lung cancer cells. Asian Pac J Cancer Prev 2014; 15: 8631-8635
- 16 Sun XY, Zheng YP, Liu ZF, Xu LL, Li S. Studies on the chemical constituents of sesquiterpenoids from Curcuma wenyujin . J Instrumental Anal 2006; 25: 27-30
- 17 Wang S, Sun XY, Zheng YP, Liu K, Zhao F. Inhibitory effect of volatile oil from Curcuma wenyujin on NO production in LPS-activated mouse macrophage. J Yantai Uni (Nat Sci Engin) 2008; 21: 71-77
- 18 Mannervik B, Board PG, Hayes JD, Listowsky I, Pearson WR. Nomenclature for mammalian soluble glutathione transferases. Methods Enzymol 2005; 401: 1-8
- 19 Ling HH, Zhou YP, Liu J. Study on mechanisms of multidrug resistance of tumors. Int J Biomed Eng 2012; 35: 57-60