Effect of Zamzam Water Extract of Curcuma zedoaria Treatment on Apoptosis, p53 and Bcl2 Protein Expression of T47D Cell Culture


  • Sultan Agung Islamic University, Department of Chemistry, Medical Faculty, Central Java Tengah, 50112, Indonesia
  • Sultan Agung Islamic University, Department of Biochemistry, Semarang, Central Java, 50112, Indonesia
  • Sultan Agung Islamic University, Department of Anatomy, Medical Faculty, Central Java, 50112, Indonesia


Introduction: People worldwide drink Zamzam water either medicinally or religiously. However, the effect of zamzam water extract of CZ in breast cancer cells remains unclear. Objective: To evaluate the zamzam water extract of CZ effect on cell apoptosis, p53 and Bcl2 protein expression in T47 D cells line culture. Methods: In the control group design, 16 Wells which was filled with T47 D cell line culture in the density of 5 × 104/100 μl, were assigned into 4 groups. Control group (C-G), were only filled with T47D cell line culture; Zamzam 50 (ZZ-50); Zamzam 100 (ZZ-100), and Zamzam 500 (ZZ-500) groups, were filled with T47D cell line cultures and 50, 100, and 500 μg/ml zamzam water extract of CZ respectively, and then incubated for 48 hours. The number of apoptotic cell was counted by flow cytometry, while p53 and Bcl2 measured by immunohistochemistry staining method. Results: Mann Whitney analysis indicated that the percentage of apoptotic cell and p53 protein expression in ZZ-100 was significant higher compared to that of C-G (p < 0.05). In contrary the percentage number of Bcl2 protein expression in ZZ100-G was significantly lower when compared to that of C-G (p < 0.05). Conclusion: Treatment of zamzam water extract of CZ on T47D cell line cultured was capable of increasing the number of apoptotic cells, p53 protein expression, but decreased Bcl2 protein expression in T47D cell line culture. However the numbers of apoptotic cells were less than 10%.


Apoptosis, Breast Cancer, Chemoprevention, Flavonoids, p53 Mutan.

Subject Discipline

biochemistry and mollecular biology

Full Text:


Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, et al. Quercetin, a Natural Flavonoid Interacts with D NA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis. Scientific Reports 2016; p. 1–13. https://doi.org/10.1038/srep24049

Jnr FNG, Anyanful A, Eliason S, Adamu SM, Debrah S. Pattern of breast cancer distribution in ghana: a survey to enhance early detection, diagnosis, and treatment. International Journal of Breast Cancer. 2016; p. 1–9

Chodidjah Widayati E, Taufiqurrachman Nasihun T. Treatment of Thyponium Flageliforme in Combination with Curcuma Zedoaria, and Phyllanthus Niruri Synergistically Enhances Apoptotic and Anti-Proliferative Effect on Breast Cancer. Journal of Natural Remedies. 2017; p. 1–8. https://doi.org/10.18311/jnr/2017/8448

Bombonati A, Sgroi DC. The molecular pathology of breast cancer progression. The Journal of Pathology.

; 223: 307–17. PMid:21125683 PMCid:PMC3069504. https://doi.org/10.1002/path.2808

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA: A Cancer Journal for Clinicians. 2008; 58(2): 71–96. https://doi.org/10.1038/s41598-018-29308-7. PMid:18287387

Luo, X. et al. The role of targeting kinase activity by natural products in cancer chemoprevention and chemotherapy (Review). Oncology Report. 2015; 34: 547–54. https://doi.org/10.3892/or.2015.4029

Zhang HW, Hu JJ, Fu RQ, Liu X, Zhang YH, Li J. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Scientific Reports. 2018; 8:11255. https://doi.org/10.1038/s41598-018-29308-7

Hadisaputri YE, Miya zaki T, Suzuki S, Kubo N, Zuhrotun A, Yokobori T, et al. Molecular characterization of antitumor effects of the rhizome extract from Curcuma zedoaria on human esophageal carcinoma cells. International Journal of Oncology. 2015; 47: 2255–63. https://doi.org/10.3892/ijo.2015.3199 PMid:26498695

Peng CH, Chiu WT, Juan CW, Mau JL, Chen CC, Peng CC, Lai EY and Chyau CC: Pivotal role of curcuminoids on the antimutagenic activity of Curcuma zedoaria extracts. Drug and Chemical Toxicology. 2010; 33: 64–76. https://doi.org/10.3109/01480540903170738 PMid:19995306

Lakshmi S, Padmaja G, Remani P. Antitumour effects of isocurcumenol isolated from curcuma zedoaria rhizomes on human and murine cancer cells. International Journal of Medicinal Chemistry. 2011; 253962: 1–13. http://dx.doi.org/10.1155/2011/253962 PMid:27429805 PMCid:PMC4939266

Rahman ASM, Wahab AN, Malek ASN. In vitro morphological assessment of apoptosis induced by anti proliferative constituents from the rhizomes of Curcuma zedoaria. Evidence-Based Complementary and Alternative Medicine. 2013; 257108: 1–14. http://dx.doi.org/10.1155/2013/257108 PMid:23762112 PMCid:PMC3671673

Meiyanto E, Hamid IS. Modulasi cyp1a1 dan gstsertaekspresi p53 dan rassetelahinduksi 7,12-dimethyl benz(ά) antrasen (dmba) dan pemberian anti karsinogenesisgynuraprocumbens dan curcuma zedoaria pada tikusgalurspraguedawley. Jurnal Penelitian Medika Eksakta. 2009; 8: 168–77.

Papademetrio DL, Trabucchi A, Cavaliere V, et al. The Cathechin flavonoid reduced proliferation and induced apoptosis of murine lymphoma cells LB02 through modulation of antiapoptotic proteins. Revista Brasileira de Farmacognosia. 2013; 23(3): 455–63. https://doi.org/10.1590/S0102-695X2013005000025

Alzeer J, Hadeed KA. Ethanol and its Halal status in food industries. Trends in Food Science & Technology. 2016; 58: 14–20. https://doi.org/10.1016/j.tifs.2016.10.018

Nassini R, Andre E, Gazzieri D, Siena Gd, Zanas A, Geppetti P, Materazzi S. A Bicarbonate-Alkaline Mineral Water Protects from Ethanol-Induced Hemorrhagic Gastric Lesions in Mice. Biological and Pharmaceutical Bulletin. 2010; 33(8): 1319–23. https://doi.org/10.1248/bpb.33.1319 PMid:20686225

Bamosa A, Elnour A, Kaatabi H, Al Meheithif A, Aleissa K, et al. Zamzam Water Ameliorates Oxidative Stress and Reduces Hemoglobin A1c in Type 2 Diabetic Patients. Journal of Diabetes and Metabolism. 2013; 4: 249. https://doi.org/10.4172/2155-6156.1000249

Shomar B. Zamzam water: Concentration of trace elements and other characteristics. Chemosphere. 2012; 86(6): 600–5. https://doi.org/10.1016/j.chemosphere.2011.10.025 PMid:22138338

Hudaya I, Nasihun T, Sumarawati T. Effect of White Turmeric Extract (Curcuma zedoaria) Using Zam-zam Solvent Compare with Ethanol Solvent Against Breast Cancer CellT47D. Sains Medika. 2015; 6(2): 52–5.

Yu S, Kim T, Yoo KH, Kang K. The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Biochemical and Biophysical Research Communications. 2017 May 6; 486(3): 752–8. https://doi.org/10.1016/j.bbrc.2017; 03.114

Deborah L Holliday and Valerie Speirs. Choosing the right cell line for breast cancer Research. Holliday and Speirs Breast Cancer Research. 2011; 13:215. https://doi.org/10.1186/bcr2889 PMid:21884641 PMCid:PMC3236329

Lim LY, Vidnovic N, Ellisen LW, Leong CO. Mutant p53 mediates survival of breast cancer cells. British Journal of Cancer. 2009; 101: 1606–12. https://doi.org/10.1038/sj.bjc.6605335 PMCid:PMC2778523

Widayati. E, Nasihun T. Treatment of Pimpinella Alpina Molk Improve Oxidative stress and Inhibit Liver Cellular Apoptosis in Rats Following UVB Irradiation: Is there Any Correlation? Bangladesh Journal of Medical Science. 2018; 17: 118–28. https://doi.org/10.3329/bjms.v17i1.35292

Taufiqurrachman. Decreased expression of caspase 3 in penis and prostate tissues of rat after the treatment with buceng (Pimpinella alpine Molk & Euricoma longifolia Jack). Medical Journal of Indonesia. 2013; 22(1): 2–8. https://doi.org/10.13181/mji.v22i1.512

Chen CC, Chen Y, Hsi YT, Chang CS, Huang LF, Ho CT, Way TD, and Yie Kao JY. Chemical Constituents and Anticancer Activity of Curcuma zedoaria Roscoe Essential Oil against Non-Small Cell Lung Carcinoma Cells in Vitro and in Vivo. Journal of Agricultural and Food Chemistry. 2013; 61(47): 11418–27. https://doi.org/10.1021/jf4026184 PMid:24199734

Tanamatayarat P, Limtrakul P, Chunsakaow S, Duangrat C. Screening of some rubiaceous Plant for Cytotoxic Activity Against Cervix Carcinoma (KB-3-1) Cell line. Thai Journal of Pharmaceutical Sciences. 2003; 27(3-4): 167–72.

Khaing SL, Omar SZ, Loo CY, Arya A, Mohebali N, Mohd MA. Identification of active extracts of Curcuma zedoaria and their real- time cytotoxic activities on ovarian cancer cells and HUVEC cells. Biomedical Research. 2017; 28(21): 9182–7.


  • There are currently no refbacks.