Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

D-Pinitol Promotes Apoptosis in MCF-7 Cells via Induction of p53 and Bax and Inhibition of Bcl-2 and NF-κB

  • Rengarajan, Thamaraiselvan (Department of Pharmacology and Environmental Toxicology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) ;
  • Nandakumar, Natarajan (Department of Pharmacology and Environmental Toxicology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) ;
  • Rajendran, Peramaiyan (NPO-International Laboratory of Biochemistry) ;
  • Haribabu, Lingaiah (Department of Pharmacology and Environmental Toxicology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) ;
  • Nishigaki, Ikuo (NPO-International Laboratory of Biochemistry) ;
  • Balasubramanian, Maruthaiveeran Periyasamy (Department of Pharmacology and Environmental Toxicology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras)
  • Published : 2014.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Development of drugs from natural products has been undergoing a gradual evoluation. Many plant derived compounds have excellent therapeutic potential against various human ailments. They are important sources especially for anticancer agents. A number of promising new agents are in clinical development based on their selective molecular targets in the field of oncology. D-pinitol is a naturally occurring compound derived from soy which has significant pharmacological activitites. Therefore we selected D-pinitol in order to evaluate apoptotic potential in the MCF-7 cell line. Human breast cancer cells were treated with different concentrations of D-pinitol and cytotoxicity was measured by MTT and LDH assays. The mechanism of apoptosis was studied with reference to expression of p53, Bcl-2, Bax and NF-kB proteins. The results revealed that D-pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, while upregulating the expression of p53, Bax and down regulating Bcl-2 and NF-kB. Thus the results obtained in this study clearly vindicated that D-pinitol induces apotosis in MCF-7 cells through regulation of proteins of pro- and anti-apoptotic cascades.

Keywords

References

  1. Adlercreutz H (2002). Phyto-oestrogens cancer. Lancet Oncol, 3, 364-73. https://doi.org/10.1016/S1470-2045(02)00777-5
  2. Andres S, Abraham K, Appel KE, Lampen A (2011). Risks benefits of dietary isoflavones for cancer. Crit Rev Toxicol, 41, 463-506. https://doi.org/10.3109/10408444.2010.541900
  3. Chen Q, Galleano M, Cederbaum AI (1997). Cytotoxicity apoptosis produced by arachidonic acid in HepG2 cells over expressing human cytochrome P450 2E1. J Biol Chem, 272, 14532-41. https://doi.org/10.1074/jbc.272.23.14532
  4. Chomczynski P, Sacchi N (1987). The single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction. Anal Biochem, 162, 156-9.
  5. Dai C, Zhang B, Liu X, et al (2013). Pyrimethamine sensitizes pituitary adenomas cells to temozolomide through cathepsin B-dependent and caspase-dependent apoptotic pathways. Int J Cancer, 133, 1982-93. https://doi.org/10.1002/ijc.28199
  6. Elumalai P, Gunadharini D, Senthilkumar K, et al (2012). Ethanolic neem (Azadirachta indica A. Juss) leaf extract induces apoptosis and inhibits the IGF signaling pathway in breast cancer cell lines. Biomed and Preven Nutri, 2, 59-68. https://doi.org/10.1016/j.bionut.2011.12.008
  7. Feng Z, Levine AR (2010). The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein. Trends in Cell Biology, 20, 427-34. https://doi.org/10.1016/j.tcb.2010.03.004
  8. Giacinti L, Giacinti C, Gabellini C, et al (2012). Scriptaid effects on breast cancer cell lines. J Cell Physiol, 227, 3426-33. https://doi.org/10.1002/jcp.24043
  9. Grivell AR, Berry MN (1996). The effect of phosphate and substrate free incubation conditions on glycolysis in Enrich ascites tumor cells. Biochem Biophys Acta, 1291, 83-8. https://doi.org/10.1016/0304-4165(96)00049-9
  10. Guo-Ping Z, Kutbuddin D (2003). Subcellular location prediction of apoptosis proteins. Proteins: Structure, Function, Bioinformatics, 50, 44-8.
  11. Kumar A, Takada Y, Boriek AM, et al (2004). Nuclear factorkB: its role in health and disease. J Mol Med, 82, 434-48.
  12. Kumar N, Raj VP, Jayshree BS, et al (2012). Elucidation of structure-activity relationship of 2-quinolone derivatives and exploration of their antitumor potential through Baxinduced apoptotic pathway. Chem Biol Drug Des, 80, 291-9. https://doi.org/10.1111/j.1747-0285.2012.01402.x
  13. Kumaravel M, Sankar P, Rukkumani R, et al (2012). Antiproliferative effect of an analog of curcumin bis- 1, 7-(2-hydroxyphenyl)-hepta-1, 6-diene-3, 5-dione in humanbreast cancer cells. Eur Rev Med Pharmacol Sci, 16, 1900-7.
  14. Kuo LN, Huang CJ, Fang YC, et al (2009). Effect of thimerosal on Ca2? movement and viability in human oral cancer cells. Hum Exp Toxicol, 28, 301-8. https://doi.org/10.1177/0960327109106548
  15. Li Y, Li D, Yuan S, et al (2013). Embelin-induced MCF-7 breast cancer cell apoptosis and blockade of MCF-7 cells in the G2/M phase via the mitochondrial pathway. Oncol Lett, 5, 1005-9. https://doi.org/10.3892/ol.2012.1084
  16. Liu-Qin Y, Dian-Chun F, Rong-Quan W, et al (2004). Effect of NF-B, surviving, Bcl-2 and caspase 3 on apoptosis of gastric cancer cells induced by tumor necrosis factor releated apoptosis inducing ligand. World J Gastroenterol, 10, 22-5. https://doi.org/10.3748/wjg.v10.i1.22
  17. Lowry OH, Rosebrough NJ, Farr AL, et al (1951). Protein measurement with the folin-phenol reagent. J Biol Chem, 193, 265-75.
  18. Ma C, Xie JW, Kuang AR, et al (2009). The effects of antisense oligonucleotides Bcl-2/Bcl-xl and Bcl-2 on proliferation and apoptosis of breast cancer cells. Sichuan Da Xue Xue Bao Yi Xue Ban, 40, 780-3.
  19. Martin Brown J, Laura D (2005). The role of apoptosis in cancer development and treatment response. Nat Rev Cancer, 5, 231-7. https://doi.org/10.1038/nrc1560
  20. Moon DO, Choi YH, Moon SK, et al (2011). Gossypol decreases tumor necrosis factor-$\alpha$-induced intercellular adhesion molecule-1 expression via suppression of NF-${\kappa}B$ activity. Food Chem Toxicol, 49, 999-1005. https://doi.org/10.1016/j.fct.2011.01.006
  21. Moron MS, Depierre JW, Mannervik B (1979). Levels of glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta, 582, 67-78. https://doi.org/10.1016/0304-4165(79)90289-7
  22. Mossmann 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
  23. Nandakumar N, Rengarajan T, Haribabu L, et al (2011). Effect of flavonone hesperidin on the apoptosis of human mammary carcinoma cell line MCF-7. Biomed Prevent Nutr, 1, 207-15. https://doi.org/10.1016/j.bionut.2011.07.001
  24. Norhaizan ME, Ng SK, Norashareena MS, et al (2011). Antioxidant and cytotoxicity effect of rice bran phytic acid as an anticancer agent on ovarian, breast and liver cancer cell lines. Malays J Nutr, 17, 367-75.
  25. Ojeswi BK, Khoobchandani M, Hazra DK, et al (2010). Protective effect of Thuja occidentalis against DMBAinduced breast cancer with reference to oxidative stress. Hum Exp Toxicol, 29, 369-75. https://doi.org/10.1177/0960327110364150
  26. Papanikolaou V, Iliopoulos D, Dimou I, et al (2011). Survivin regulation by HER2 through NF-${\kappa}B$ and c-myc in irradiated breast cancer cells. J Cell Mol Med, 15, 1542-50. https://doi.org/10.1111/j.1582-4934.2010.01149.x
  27. Phillips DV, Dougherty DE, Smith AE (1982). Cyclitols in soybean. J Agri Food Chem, 30, 456-8. https://doi.org/10.1021/jf00111a011
  28. Ping-Chi H, Yu-Ting H, Mei-Ling T, et al (2004). Induction of apoptosis by shikonin through coordinative modulation of the Bcl-2 family, p27, and p53, release of cytochrome c, and sequential activation of caspases in human colorectal carcinoma cells. J Agric Food Chem, 52, 6330-7. https://doi.org/10.1021/jf0495993
  29. Prasanna R, Harish CC, Pichai R, et al (2009). Anti-cancer effect of Cassia auriculata leaf extract in vitro through cell cycle arrest and induction of apoptosis in human breast and larynx cancer cell lines. Cell Biol Inter, 33, 127-34. https://doi.org/10.1016/j.cellbi.2008.10.006
  30. Sato A, Kudo C, Yamakoshi H, et al (2011). Curcumin analog GO-Y030 is a novel inhibitor of IKKb that suppresses NF-${\kappa}B$ signaling and induces apoptosis. Cancer Sci, 102, 1045-51. https://doi.org/10.1111/j.1349-7006.2011.01886.x
  31. Sethi G, Ahn KS, Sung B, et al (2008). Pinitol targets nuclear factor-KB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis. Mol Cancer Ther, 7, 1604-14. https://doi.org/10.1158/1535-7163.MCT-07-2424
  32. Sivakumar S, Palsamy P, Subramanian S (2010). Impact of D-pinitol on the attenuation of proinflammatory cytokines, hyperglycemia-mediated oxidative stress and protection of kidney tissue ultrastructure in streptozotocin-induced diabetic rats. Chem Biol Interact, 188, 237-45. https://doi.org/10.1016/j.cbi.2010.07.014
  33. Sivalokanathan S, Vijayababu MR, Balasubramanian MP (2006). Effects of Terminalia arjuna bark extract on apoptosis of human hepatoma cell line HepG2. World J Gastroenterol, 12, 1018-24. https://doi.org/10.3748/wjg.v12.i7.1018
  34. Tathagata C, Suman P, Munna LA, et al (2002). Curcumin induces apoptosis in human breast cancer cells through p53- dependent Bax induction. FEBS, 512, 334-40. https://doi.org/10.1016/S0014-5793(02)02292-5
  35. Veronique B, Michael K (2009). Is NF-KB a good target for cancer therapy? Hopes pitfalls. Nat Rev Drug Discov, 8, 33-40. https://doi.org/10.1038/nrd2781
  36. Wang CY, Mayo MW, Korneluk RG, et al (1998). NFkappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science, 281, 1680-3. https://doi.org/10.1126/science.281.5383.1680
  37. Williams JL, Ji P, Ouyang N, et al (2008). NO-donating aspirin inhibits the activation of NF-kappaB in human cancer cell lines and Min mice. Carcinogenesis, 29, 390-7. https://doi.org/10.1093/carcin/bgm275
  38. Wu X, Hawse JR, Subramaniam M, et al (2009). The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor $\alpha$ for degradation in breast cancer cells. Cancer Res, 69, 1722. https://doi.org/10.1158/0008-5472.CAN-08-3933
  39. Xuea L, Schaldach CM, Janosik T, et al (2005). Effects of analogs of indole-e-carbinol cyclic trimerization product in human breast cancer cells. Chem Biol Interact, 152, 119-29. https://doi.org/10.1016/j.cbi.2005.02.007
  40. Zuo YB, Zeng AW, Yuan XG, Yu KT (2008). Extraction of soybean isoflavones from soybean meal with aqueous methanol modified supercritical carbon dioxide. J Food Eng, 89, 384-9. https://doi.org/10.1016/j.jfoodeng.2008.05.004

Cited by

  1. Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway vol.15, pp.13, 2014, https://doi.org/10.7314/APJCP.2014.15.13.5201
  2. Breast Cancer: Major Risk Factors and Recent Developments in Treatment vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3353
  3. Curcumin a potent cancer preventive agent: Mechanisms of cancer cell killing vol.6, pp.4, 2014, https://doi.org/10.1556/IMAS.6.2014.4.1
  4. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation vol.10, pp.8, 2015, https://doi.org/10.1371/journal.pone.0136527
  5. Overexpression of Cyclin E and its Low Molecular Weight Isoforms Cooperate with Loss of p53 in Promoting Oncogenic Properties of MCF-7 Breast Cancer Cells vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7575
  6. Inhibits Proliferation and Mediates Suppression of Migration via DLC1/RhoA Signaling in Cancer Cells vol.16, pp.4, 2015, https://doi.org/10.7314/APJCP.2015.16.4.1637
  7. Isolation and identification of ingredients inducing cancer cell death from the seeds of Alpinia galanga, a Chinese spice vol.6, pp.2, 2015, https://doi.org/10.1039/C4FO00709C
  8. d-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB vol.71, pp.2, 2015, https://doi.org/10.1007/s13105-015-0397-9
  9. Effects of Epothilone A in Combination with the Antidiabetic Drugs Metformin and Sitagliptin in HepG2 Human Hepatocellular Cancer Cells: Role of Transcriptional Factors NF-κB and p53 vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.993
  10. 4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling vol.32, pp.3, 2016, https://doi.org/10.1002/tox.22274
  11. Circadian clock gene Per2 plays an important role in cell proliferation, apoptosis and cell cycle progression in human oral squamous cell carcinoma vol.35, pp.6, 2016, https://doi.org/10.3892/or.2016.4724
  12. Oleanolic acid rejuvenates testicular function through attenuating germ cell DNA damage and apoptosis via deactivation of NF-κB, p53 and p38 signalling pathways vol.69, pp.3, 2016, https://doi.org/10.1111/jphp.12668
  13. Psoralidin inhibits proliferation and enhances apoptosis of human esophageal carcinoma cells via NF-κB and PI3K/Akt signaling pathways vol.12, pp.2, 2016, https://doi.org/10.3892/ol.2016.4716
  14. In Vitro and In Vivo Inhibitory Effect of Gujin Xiaoliu Tang in Non-Small Cell Lung Cancer vol.2018, pp.1741-4288, 2018, https://doi.org/10.1155/2018/8936108