Nordamnacanthal potentiates the cytotoxic effects of tamoxifen in human breast cancer cells

Subramani,Tamilselvan; Yeap,Swee  Keong; Ho,Wan  Yang; Ho,Chai  Ling; Osman,Che  Puteh; Ismail,Nor  Hadiani; Nik Abdul Rahman,Nik  Mohd Afizan; Alitheen,Noorjahan  Banu

doi:10.3892/ol.2014.2697

Nordamnacanthal potentiates the cytotoxic effects of tamoxifen in human breast cancer cells

Authors:
- Tamilselvan Subramani
- Swee Keong Yeap
- Wan Yang Ho
- Chai Ling Ho
- Che Puteh Osman
- Nor Hadiani Ismail
- Nik Mohd Afizan Nik Abdul Rahman
- Noorjahan Banu Alitheen
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Affiliations: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia, Faculty of Medicine and Health Science, School of Biomedical Sciences, The University of Nottingham Malaysia Campus, Semenyih, Selangor 43500, Malaysia, Faculty of Applied Sciences, Universiti Teknologi Mara, Shah Alam, Selangor 40450, Malaysia
Published online on: November 10, 2014 https://doi.org/10.3892/ol.2014.2697
Pages: 335-340

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Abstract

Tamoxifen (TAM) is the mainline drug treatment for breast cancer, despite its side effects and the development of resistance. As an alternative approach, in the present study a novel combination therapy was established through combining TAM with nordamnacanthal (NDAM) in order to investigate the additive effect of these drugs in MCF‑7 human breast cancer cells. A significant dose‑dependent reduction in cell viability and an increase in apoptosis were observed in the MCF‑7 cells cotreated with TAM and NDAM compared with the untreated control cells or the cells treated with TAM and NDAM alone (P<0.05). The cytotoxic influence of the combination of TAM and NDAM was found to be two‑fold that of the individual agents. Annexin V/propidium iodide double‑staining revealed the typical nuclear features of apoptosis. Furthermore, an increase in the proportion of apoptotic, Annexin V‑positive cells was observed with the combination therapy. Moreover, this apoptotic induction was associated with a collapse of the mitochondrial membrane potential and the generation of reactive oxygen species. To the best of our knowledge, the findings of the present study are the first to suggest that combining TAM with NDAM may be a potential combination therapy for the treatment of breast cancer and may have the potential to minimize or eliminate the side effects associated with high doses of TAM.

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1	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI
2	Goldhirsch A, Ingle JN, Gelber RD, et al: Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 20:1319–1329. 2009. View Article : Google Scholar : PubMed/NCBI
3	Radmacher MD and Simon R: Estimation of tamoxifen’s efficacy for preventing the formation and growth of breast tumors. J Natl Cancer Inst. 92:48–53. 2000. View Article : Google Scholar : PubMed/NCBI
4	Early Breast Cancers Trialists’ collaborative group. Tamoxifen for an early breast cancer: an overview of the randomised trials. Lancet. 351:1451–1467. 1998. View Article : Google Scholar
5	Love RR: Tamoxifen therapy in primary breast cancer: biology, efficacy, and side effects. J Clin Oncol. 7:803–815. 1989.PubMed/NCBI
6	Marshall E: Tamoxifen: ‘a big deal,’ but a complex hand to play. Science. 280:1961998. View Article : Google Scholar
7	Parvez S, Tabassum H, Rehman H, et al: Catechin prevents tamoxifen-induced oxidative stress and biochemical perturbations in mice. Toxicology. 225:109–118. 2006. View Article : Google Scholar : PubMed/NCBI
8	Conklin KA: Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther. 3:294–300. 2004. View Article : Google Scholar : PubMed/NCBI
9	Fisher B, Constantino JP, Wickerham CD, et al: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 90:1371–1388. 1998. View Article : Google Scholar : PubMed/NCBI
10	Fornander T, Rutqvist LE, Cedermark B, et al: Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet. 1:117–120. 1989. View Article : Google Scholar : PubMed/NCBI
11	Johnston SR, Dowsett M and Smith IE: Towards a molecular basis for tamoxifen resistance in breast cancer. Ann Oncol. 3:503–511. 1992.PubMed/NCBI
12	Osborne CK: Tamoxifen in the treatment of breast cancer. N Engl J Med. 339:1609–1618. 1998. View Article : Google Scholar : PubMed/NCBI
13	Ismail NH, Ali AM, Aimi N, et al: Anthraquinones from Morinda elliptica. Phytochemistry. 45:1723–1725. 1997. View Article : Google Scholar
14	Yazan LS, Ishak N and Lajis NH: BCL-2 was downregulated in G2/M-arrest breast cancer cells MCF-7-treated with Nordamnacanthal. J Pharm Sci & Res. 2:197–207. 2010.
15	Jasril, Lajis NH, Mooi LY, Abdullah MA, Sukari MA and Ali AM: Antitumor promoting and antioxidant activities of anthraquinones isolated from cell suspension culture of Morinda elliptica. Asia Pac J Mol Biol Biotechnol. 11:3–7. 2003.
16	Kamiya K, Hamabe W, Tokuyama S, et al: Inhibitory effect of anthraquinones isolated from the noni (Morinda citrifolia) root on animal A-, B-, and Y-families of DNA polymerases and human cancer cell proliferation. Food Chem. 118:725–730. 2009. View Article : Google Scholar
17	Frank J, Kelleher DK, Pompella A, et al: Enhancement of oxidative cell injury and antitumor effects of localized 44 degrees C hyperthermia upon combination with respiratory hyperoxia and xanthine oxidase. Cancer Res. 58:2693–2698. 1998.PubMed/NCBI
18	Jentzsch AM, Bachmann H, Furst P and Biesalski HK: Improved analysis of malondialdehyde in human body fluids. Free Radic Biol Med. 20:251–256. 1996. View Article : Google Scholar : PubMed/NCBI
19	Johnston SR: Acquired tamoxifen resistance in human breast cancer - potential mechanisms and clinical implications. Anticancer Drugs. 8:911–930. 1997. View Article : Google Scholar
20	Danova M, Pellicciari C, Zibera C, et al: Cell cycle kinetic effects of tamoxifen on human breast cancer cells. Flow cytometric analyses of DNA content, BrdU labeling, Ki-67, PCNA, and statin expression. Ann NY Acad Sci. 698:174–181. 1993. View Article : Google Scholar : PubMed/NCBI
21	Osborne CK, Boldt DH, Clark GM and Trent JM: Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase. Cancer Res. 43:3583–3585. 1983.PubMed/NCBI
22	Li S, Zhou Y, Wang R, et al: Selenium sensitizes MCF-7 breast cancer cells to doxorubicin-induced apoptosis through modulation of phospho-Akt and its downstream substrates. Mol Cancer Ther. 6:1031–1038. 2007. View Article : Google Scholar : PubMed/NCBI
23	Li Z, Carrier L and Rowan BG: Methylseleninic acid synergizes with tamoxifen to induce caspase-mediated apoptosis in breast cancer cells. Mol Cancer Ther. 7:3056–3063. 2008. View Article : Google Scholar : PubMed/NCBI
24	Green DR and Reed JC: Mitochondria and apoptosis. Science. 281:1309–1312. 1998. View Article : Google Scholar : PubMed/NCBI