BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Cell Cycle Regulation and Induction of Apoptosis by β-carotene in U937 and HL-60 Leukemia Cells

  • Upadhyaya, K.R. (R&D division, Bayier Extracts Ltd) ;
  • Radha, K.S. (Department of Applied Physiology, Faculty of Medicine, University of Miyazaki) ;
  • Madhyastha, H.K. (Department of Applied Physiology, Faculty of Medicine, University of Miyazaki)
  • Published : 2007.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

In this communication, we report the efficacy of $\beta$-carotene towards differentiation and apoptosis of leukemia cells. Dose ($20{\mu}M$) and time dependence (12 h) tests of $\beta$-carotene showed a higher magnitude of decrease (significance p < 0.05) in cell numbers and cell viability in HL-60 cells than U937 cells but not normal cell like Peripheral blood mononuclear cell (PBMC). Microscopical observation of $\beta$-carotene treated cells showed a distinct pattern of morphological abnormalities with inclusion of apoptotic bodies in both leukemia cell lines. When cells were treated with $20{\mu}M$ of $\beta$-carotene, total genomic DNA showed a fragmentation pattern and this pattern was clear in HL-60 than U937 cells. Both the cell lines, on treatment with $\beta$-carotene, showed a clear shift in $G_1$ phase of the cell cycle. In addition the study also revealed anti-oxidant properties of $\beta$-carotene since there was reduction in relative fluorescent when treated than the control at lower concentration. Collectively this study shows the dual phenomenon of apoptosis and differentiation of leukemia cells on treatment with $\beta$-carotene.

Keywords

References

  1. Aggarwal, B. B. and Shishodia, S. (2006) Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharmacol. 71, 1397-1421. https://doi.org/10.1016/j.bcp.2006.02.009
  2. Altucci, L., Rossin, A., Raffelsberger, W., Reitmair, A., Chomienne, C. and Gronemeyer, H. (2001) Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Nat. Med. 7, 680-686. https://doi.org/10.1038/89050
  3. Amir, H., Karas, M., Giat, J., Danilenko, M., Levy, R., Yermiahu, T., Levy, J. and Sharoni, Y. (1999) Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells. Nutr. Cancer 33, 105-112. https://doi.org/10.1080/01635589909514756
  4. Bortuzzo, C., Hanif, R., Kashfi, K., Staiano-Coico, L., Shiff, S. J. and Rigas, B. (1996) The effect of leukotrienes B and selected HETEs on the proliferation of colon cancer cells. Biochim. Biophys. Acta 1300, 240-246. https://doi.org/10.1016/0005-2760(96)00003-3
  5. Burkitt, M. J. and Wardman, P. (2001) Cytochrome C is a potent catalyst of dichlorofluorescin oxidation: implications for the role of reactive oxygen species in apoptosis. Biochem. Biophys. Res. Commun. 282, 329-333. https://doi.org/10.1006/bbrc.2001.4578
  6. Collins, S. J. (2002) The role of retinoids and retinoic acid receptors in normal hematopoiesis. Leukemia 16, 1896-1905. https://doi.org/10.1038/sj.leu.2402718
  7. Covacci, V., Bruzzese, N., Sgambato, A., Di Francesco, A., Russo, M. A., Wolf, F. I. and Cittadini, A. (1998) Magnesium restriction induces granulocytic differentiation and expression of p27Kip1 in human leukemic HL-60 cells. J. Cell. Biochem. 70, 313-322. https://doi.org/10.1002/(SICI)1097-4644(19980901)70:3<313::AID-JCB4>3.0.CO;2-Q
  8. Esposito, F., Russo, L., Russo, T. and Cimino, F. (2000) Retinoblastoma protein dephosphorylation is an early event of cellular response to prooxidant conditions. FEBS Lett. 470, 211-215. https://doi.org/10.1016/S0014-5793(00)01318-1
  9. Genkinger, J. M., Hunter, D. J., Spiegelman, D., Anderson, K. E., Arslan, A., Beeson, W. L., Buring, J. E., Fraser, G. E., Freudenheim, J. L., Goldbohm, R. A., Hankinson, S. E., Jacobs, D. R., Jr., Koushik, A., Lacey, J. V., Jr., Larsson, S. C., Leitzmann, M., McCullough, M. L., Miller, A. B., Rodriguez, C., Rohan, T. E., Schouten, L. J., Shore, R., Smit, E., Wolk, A., Zhang, S. M. and Smith-Warner, S. A. (2006) Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol. Biomarkers Prev. 15, 364-372.畦Η⨀Ԁ畦Η⨀඗⨀ᔀĀ섂돀ᢉ඗⨀堘?⨀傏඗⨀餂돐炏඗⨀つᖗ⨀碏඗⨀䄀덀袏඗⨀䀀 ㄂돐좌඗⨀ꢚ඗⨀ꢚ඗⨀ https://doi.org/10.1158/1055-9965.EPI-05-0484
  10. Herrmann, M., Lorenz, H.-M., Voll, R., Griinke, M., Woith, W. and Kalden, J. R. (1994) A rapid and simple method for the isolation of apoptotic DNA fragments 10.1093/nar/22.24.5506. Nucleic Acids Res. 22, 5506-5507.
  11. Jarrett, S. G., Cuenco, J. and Boulton, M. (2006) Dietary antioxidants provide differential subcellular protection in epithelial cells. Redox Rep. 11, 144-152. https://doi.org/10.1179/135100006X116646
  12. Jing, Y., Ohizumi, H., Kawazoe, N., Hashimoto, S., Masuda, Y., Nakajo, S., Yoshida, T., Kuroiwa, Y. and Nakaya, K. (1994) Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells. Jpn. J. Cancer Res. 85, 645-651. https://doi.org/10.1111/j.1349-7006.1994.tb02408.x
  13. Konishi, I., Hosokawa, M., Sashima, T., Kobayashi, H., Miyashita, K. (2006) Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi induce apoptosis in human leukemia, breast and colon cancer cells. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 142, 53-59. https://doi.org/10.1016/j.cbpc.2005.10.005
  14. Koushik, A., Hunter, D. J., Spiegelman, D., Anderson, K. E., Buring, J. E., Freudenheim, J. L., Goldbohm, R. A., Hankinson, S. E., Larsson, S. C., Leitzmann, M., Marshall, J. R., McCullough, M. L., Miller, A. B., Rodriguez, C., Rohan, T. E., Ross, J. A., Schatzkin, A., Schouten, L. J., Willett, W. C., Wolk, A., Zhang, S. M. and Smith-Warner, S. A. (2006) Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies. Int. J. Cancer 119, 2148-2154.ᄈ돀顡⨀堘?⨀㣩?⨀돐炵?⨀炵?⨀〰㝟瘴の㙟㄰〹 https://doi.org/10.1002/ijc.22076
  15. Maillard, V., Hoinard, C., Arab, K., Jourdan, M. L., Bougnoux, P. and Chajes, V. (2006) Dietary $\beta$-carotene inhibits mammary carcinogenesis in rats depending on dietary alpha-linolenic acid content. Br. J. Nutr. 96, 18-21. https://doi.org/10.1079/BJN20061781
  16. Matsuno-Yagi, A. and Hatefi, Y. (1996) Ubiquinol-cytochrome c oxidoreductase. The redox reactions of the bis-heme cytochrome b in ubiquinone-sufficient and ubiquinone-deficient systems. J. Biol. Chem. 271, 6164-6171. https://doi.org/10.1074/jbc.271.11.6164
  17. McCarty, M. F. and Block, K. I. (2006) Toward a core nutraceutical program for cancer management. Integr. Cancer Ther. 5, 150-171. https://doi.org/10.1177/1534735406288443
  18. Mosmann, T. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  19. Murakoshi, M., Takayasu, J., Kimura, O., Kohmura, E., Nishino, H., Iwashima, A., OkuzuMi, J., Sakai, T., Sugimoto, T., Imanishi, J. and et al. (1989) Inhibitory effects of alpha-carotene on proliferation of the human neuroblastoma cell line GOTO. J. Natl. Cancer Inst. 81, 1649-1652. https://doi.org/10.1093/jnci/81.21.1649
  20. Neuhouser, M. L., Patterson, R. E., Thornquist, M. D., Omenn, G. S., King, I. B. and Goodman, G. E. (2003) Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the $\beta$-carotene and retinol efficacy trial (CARET). Cancer Epidemiol. Biomarkers Prev. 12, 350-358.
  21. Noguchi, P. D. and Browne, W. C. (1978) The use of chicken erythrocyte nuclei as a biological standard for flow microfluorometry. J. Histochem. Cytochem. 26, 761-763.
  22. Phalen, T. J., Weirather, K., Deming, P. B., Anathy, V., Howe, A. K., Van der Vliet, A., Jonsson, T. J., Poole, L. B., Heintz, N. H. (2006) Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery. J. cell boil. 175, 779-89. https://doi.org/10.1083/jcb.200606005
  23. Palozza, P., Serini, S., Torsello, A., Boninsegna, A., Covacci, V., Maggiano, N., Ranelletti, F. O., Wolf, F. I. and Calviello, G. (2002) Regulation of cell cycle progression and apoptosis by $\beta$-carotene in undifferentiated and differentiated HL-60 leukemia cells: possible involvement of a redox mechanism. Int. J. Cancer 97, 593-600. https://doi.org/10.1002/ijc.10094
  24. Paolini, M., Abdel-Rahman, S. Z., Sapone, A., Pedulli, G. F., Perocco, P., Cantelli-Forti, G. and Legator, M. S. (2003) $\beta$- carotene: a cancer chemopreventive agent or a co-carcinogen? Mutat. Res. 543, 195-200. https://doi.org/10.1016/S1383-5742(03)00002-4
  25. Prakash, P., Jackson, C. L. and Gerber, L. E. (1999) Sub-cellular accumulation of $\beta$-carotene and retinoids in growth-inhibited NCI-H69 small cell lung cancer cells. Nutr. Cancer 34, 76-82. https://doi.org/10.1207/S15327914NC340111
  26. Quick, T. C. and Ong, D. E. (1990) Vitamin A metabolism in the human intestinal Caco-2 cell line. Biochemistry 29, 11116-11123. https://doi.org/10.1021/bi00502a015
  27. Schreinemachers, D. M. and Everson, R. B. (1994) Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 5, 138-146. https://doi.org/10.1097/00001648-199403000-00003
  28. Schwartz, J. L. (1993) In vitro biological methods for determination of carotenoid activity. Methods Enzymol. 214, 226-256. https://doi.org/10.1016/0076-6879(93)14069-U

Cited by

  1. Analysis of microRNA expression profiles during the cell cycle in synchronized HeLa cells vol.42, pp.9, 2009, https://doi.org/10.5483/BMBRep.2009.42.9.593
  2. Influence of Lycopene on Cell Viability, Cell Cycle, and Apoptosis of Human Prostate Cancer and Benign Hyperplastic Cells vol.65, pp.7, 2013, https://doi.org/10.1080/01635581.2013.812225
  3. Bioactive Chemicals from Carrot (Daucus carota)Juice Extracts for the Treatment of Leukemia vol.14, pp.11, 2011, https://doi.org/10.1089/jmf.2010.0284
  4. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides vol.19, pp.7, 2015, https://doi.org/10.1111/jcmm.12546
  5. Effects of Caffeic and 5-Caffeoylquinic Acids on Cell Viability and Cellular Uptake in Human Colon Adenocarcinoma Cells vol.67, pp.3, 2015, https://doi.org/10.1080/01635581.2015.1004736
  6. Naturally occurring immunomodulators with antitumor activity: An insight on their mechanisms of action vol.50, 2017, https://doi.org/10.1016/j.intimp.2017.07.010
  7. Inhibition of Proliferation and Induction of Apoptosis by the Combination of β-carotene and 1,25-dihydroxyvitamin D3 in Human Esophageal Cancer EC9706 Cells vol.13, pp.12, 2012, https://doi.org/10.7314/APJCP.2012.13.12.6327
  8. Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells vol.1810, pp.5, 2011, https://doi.org/10.1016/j.bbagen.2011.02.008
  9. Carotenoids modulate the hallmarks of cancer cells vol.18, 2015, https://doi.org/10.1016/j.jff.2014.10.017
  10. β-Carotene exhibits antioxidant and anti-apoptotic properties to prevent ethanol-induced cytotoxicity in isolated rat hepatocytes vol.24, pp.S2, 2010, https://doi.org/10.1002/ptr.3068
  11. TC1 (C8orf4) is involved in ERK1/2 pathway-regulated G1- to S-phase transition vol.41, pp.10, 2008, https://doi.org/10.5483/BMBRep.2008.41.10.733
  12. β-carotene Regulates the Murine Liver Microenvironment of a Metastatic Neuroblastoma vol.18, pp.4, 2013, https://doi.org/10.15430/JCP.2013.18.4.337
  13. Induction of Necrosis in Human Liver Tumor Cells by α-Phellandrene vol.66, pp.6, 2014, https://doi.org/10.1080/01635581.2014.936946
  14. Dunaliella salinaExhibits an Antileukemic Immunity in a Mouse Model of WEHI-3 Leukemia Cells vol.62, pp.47, 2014, https://doi.org/10.1021/jf503564b