Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis via Mitochondrial Pathway in Human Lung Adenocarcinoma A549 Cells

  • Authors

    • Radiah Abdul Ghani
    • Nik Nurasyikin Nik Abdul Malek
    • Norzamzila Abdullah
    2018-08-24
    https://doi.org/10.14419/ijet.v7i3.30.18268
  • apoptosis, caspases, mitochondria permeability, lung cancer, pomegranate juice
  • Lung cancer is the most common type of cancer which the mortality rate increases year by year. Therapeutic drugs could not control the progression of cancer and it contributes to the side effects in normal cells. Thus, an alternative strategy using natural product becomes a focus today. Punica granatum, known as pomegranate has demonstrated the anti-proliferative effect in A549 cells. To further confirm its efficacy, this study aimed to investigate the type of cell death and its pathway in A549 cells. Propium Iodide staining was applied to determine the cell cycle profile changes induced by this juice. The determination of type of cell death was done using Annexin-V staining and later will be analysed using flowcytometer. The pathway to apoptosis was investigated by determining the caspase- 3, 8 and 9 activities. The findings were supported by mitochondrial membrane permeability assay and cytochrome c release detection which were later analysed using flowcytometer. This study revealed that pomegranate juice induced cell cycle arrest at G0/G1 phase and apoptosis through intrinsic pathway following 24 h treatment. Pomegranate juice caused loss of mitochondrial membrane permeability after 48 h [p<0.05] exposure and a release of cytochrome c in cytosol after 24 h [p<0.05] and 48 h [p<0.01] exposure in treated A549 cells. In caspases analysis, it was showed that there was activation of caspase-3 following 72 h [p<0.01] treatment and caspase-9 after 48 [p<0.01] and 72 h [p<0.05] exposure in treated A549 cells. It can be concluded that pomegranate juice able to cause A549 cell growth inhibition by inducing cell cycle arrest and apoptosis through mitochondrial pathway.

     

  • References

    1. [1] Abdul Ghani, R., Jamil E.F, Nor Azahan Shah NAM, Nik Abdul Malek, NNA. The role of polyamines in anti-proliferative effect of selected malaysian herbs in human lungadenocarcinoma cell line. Jurnal Teknologi,2015. 77 (25) , 0 pp. 137-140

      [2] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30

      [3] Gullet, N. P., Ruhul Amin, A. R. M., Bayraktar, S., Pezzuto, J. M., Shin, D. M., Khuri, F. R., Aggarwal, B. B., Surh, Y., & Kucuk, O. Cancer prevention with natural compounds. Seminars in Oncology.2010. 37(3): 258-281

      [4] Saunders, F. R., & Wallace, H. M. On the natural chemoprevention of cancer. Plant Physiology and Biochemistry.2010, 48: 621-626

      [5] Abdul Ghani,R., Nik Abdul Malek, NNA, Md Yusof, NF, Jamil EF. Ornithine decarboxylase gene expression in human lung adenocarcinoma cell (A549) treated with pomegranate juice. Jurnal Teknologi, 2015, 77 (25). , 0 pp. 95-99

      [6] Turrini, E., Ferruzzi, L., & Fimognari, C. Potential effects of pomegranate polyphenols in cancer prevention and therapy. Oxidative Medicine and Cellular Longevity, 2015.

      [7] Adams, L. S., Zhang, Y., Seeram, N. P., Haber, D., & Chen, S. Pomegranate ellagitannin-derived compounds exhibit anti-proliferative and antiaromatase activity in breast cancer cells in vitro. Cancer Prevention Research, 2010, 3(1): 108-113

      [8] Jaganathan, S. K., Vellayappan, M. V., Narasimhan, G., & Supriyanto, E.Role of pomegranate and citrus fruit juices in colon cancer prevention. World Journal of Gastroenterology.2014, 20(16): 4618-4625

      [9] Nair, V., Dai, Z., Khan, M., & Ciolino, H. P. Pomegranate extract induces cell cycle arrest and alters cellular phenotype of human pancreatic cancer cells. Anticancer Research. 2011, 31: 2699-2704

      [10] Andrew Palmer, Radiah Abdul Ghani, Navneet Kaur, Otto Phanstiel, Heather Wallace.A putrescine¿anthracene conjugate : a paradigm for selective drug delivery. Biochemical Journal, 2009, 424. , 0 pp. 431- 438

      [11] Ouyang, L., Shi, Z., Zhao, S., Wang, F.T., Zhou§, T. T., Liu, B., & Bao, J. K. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Proliferation.2012, 45(6): 487-498

      [12] Viurda-Martos, M., Fernández-López, J., & Pérez-Ãlvarez, J. A. Pomegranate and its many fuctional components as related to human helath: a review. Comprehensive Reviews in Food Science and Food Safety.2010, 9: 635-654

      [13] Lansky, N., Newman, R. A. Punica grantum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. Journal of Ethnopharmacology. 2007, 109(2): 177-206

      [14] Khan, N., Afaq, F., Kweon, M., Kim, K., & Mukhtar, H.Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice. Cancer Research. 2007, 67(7): 3475-3482

      [15] McIlwain, D. R., Berger, T., & Mak, T. W. Caspase function in cell death and disease. Cold Spring Harbor Perspectives in Biology, 2013.

      [16] Sakaue-Sawano, A., Kobayashi, T., Ohtawa, K., & Miyawaki, A. Drug-induced cell cycle modulation leading to cell-cycle arrest, nuclear mis-segregation, or endoreplication. BMC Cell Biology. 2011, 12: 1-12

      [17] Dikmen, M., Ozturk, N., & Ozturk, Y.The antioxidant potency of punica granatum L. fruit peel reduces cell proliferation and induces apoptosis on breast cancer. Journal of Medicinal Food. 2011,14(12): 1638-1646

      [18] Kiraz, Y., Neergheen-Bhujun, V. S., Rummun, N., & Baran, Y. Apoptotic effects of non-edible parts of punica granatum on human multiple myeloma cells. Tumor Biology. 2015, 1-13

      [19] Ismail, T., Sestili, P., & Akhtar, S.Pomegranate peel and fruit extracts: a review of potential anti-inflammatory and anti-infective effects. Journal of Ethnopharmacology. 2012,143(2): 397-405

  • Downloads

  • How to Cite

    Abdul Ghani, R., Nurasyikin Nik Abdul Malek, N., & Abdullah, N. (2018). Pomegranate Juice Induced Cell Cycle Arrest and Apoptosis via Mitochondrial Pathway in Human Lung Adenocarcinoma A549 Cells. International Journal of Engineering & Technology, 7(3.30), 309-313. https://doi.org/10.14419/ijet.v7i3.30.18268