DOI QR코드

DOI QR Code

Betaine Effects on Morphology, Proliferation, and p53-induced Apoptosis of HeLa Cervical Carcinoma Cells in Vitro

  • Guo, Yu (Bioscience Department, Department of Biochemistry and Molecular Biology, Bengbu Medical College) ;
  • Xu, Li-Sha (Bioscience Department, Department of Biochemistry and Molecular Biology, Bengbu Medical College) ;
  • Zhang, Ding (Bioscience Department, Department of Biochemistry and Molecular Biology, Bengbu Medical College) ;
  • Liao, Ya-Ping (Bioscience Department, Department of Biochemistry and Molecular Biology, Bengbu Medical College) ;
  • Wang, Hai-ping (Bioscience Department, Department of Biochemistry and Molecular Biology, Bengbu Medical College) ;
  • Lan, Zhi-Hui (Bioscience Department, Department of Biochemistry and Molecular Biology, Bengbu Medical College) ;
  • Guan, Wei-Jun (Institute of Animal Science, Chinese Academy of Agricultural Science) ;
  • Liu, Chang-Qing (Bioscience Department, Department of Biochemistry and Molecular Biology, Bengbu Medical College)
  • 발행 : 2015.04.29

초록

Objectives: To investigate the effects of betaine on HeLa cell growth and apoptosis and molecular mechanisms. Materials and Methods: Concentrations of 0.1, 1.0, 5.0, 20.0, 100.0 mg/ml of betaine were used to evaluate the anticancer efficacy for HeLa cells respectively, and MCF-10A was also detected as a normal diploid cell control. Results: We found that proliferation of HeLa cells was inhibited significantly upon exposure to increasing betaine levels with the MTT test (p<0.05). The percentage of S phase cells in the low dose groups (<5mg/ml) were distinctly higher than in high dose groups, and the rates of Sub-G1 phase were the opposite (p<0.01); A high concentration of betaine (>5.0mg/ml) significantly promoted the apoptosis of HeLa cells (p<0.01). SOD activities of the low dose groups were slightly higher than the control group (p<0.05) and there were obvious synchronicity and correlation among the expression of promoting apoptosis genes Bax, P53, Caspase 3 and apoptosis suppression gene Bcl-2. In response to an apoptosis-inducing stimulus, p53 and cyclin D1 could be activated with blockage of the cell cycle at G1/S or S/G2 checkpoints. Conclusions: Our data showed that betaine could promote HeLa cells proliferation in vitro at low concentrations. In contrast, high concentrations could significantly inhibit cell growth and migration, and induce apoptosis of HeLa cells through caspase 3 signaling and further promoted necrosis. This might imply that betaine exhibits tumoricidal effects and acts as a biological response modifier in cancer treatment by inducing apoptosis and cell cycle arrest in a dose and time-dependent manner.

키워드

참고문헌

  1. Abrahim NN, Kanthimathi MS, Abdul-Aziz A (2012). Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase. BMC Complement Altern Med, 12, 220. https://doi.org/10.1186/1472-6882-12-220
  2. Du YP, Peng JS, Sun A, et al (2009). Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model. BMC Cancer, 9, 261. https://doi.org/10.1186/1471-2407-9-261
  3. Duong FH, Christen V, Filipowicz M, et al (2006). S-Adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro. Hepatology, 43, 796-806. https://doi.org/10.1002/hep.21116
  4. Franco R, Schoneveld O, Georgakilas AG, et al (2008). Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett, 266, 6-11. https://doi.org/10.1016/j.canlet.2008.02.026
  5. Gerile Sogawa C, Ohyama K, et al (2012). Inhibitory action of antidepressants on mouse betaine/GABA transporter (BGT1) heterologously expressed in cell cultures. Int J Mol Sci, 13, 2578-89. https://doi.org/10.3390/ijms13032578
  6. Guo Y, Liao YP, Zhang D, et al (2014). In vitro study of nucleostemin as a potential therapeutic target in human breast carcinoma SKBR-3 cells. Asian Pac J Cancer Prev, 15, 2291-5. https://doi.org/10.7314/APJCP.2014.15.5.2291
  7. Hamed AH, Shepard MK, Maglinte DD, et al (2012). Neoadjuvant chemotherapy followed by simultaneous robotic radical trachelectomy and reversal of tubal sterilization in stage IB2 cervical cancer. JSLS, 16, 650-3. https://doi.org/10.4293/108680812X13517013316555
  8. Hnilicova J, Hozeifi S, Duskova E, et al (2011). Histone deacetylase activity modulates alternative splicing. PLoS ONE, 6, 16727. https://doi.org/10.1371/journal.pone.0016727
  9. Iorio E, Ricci A, Bagnoli M, et al (2010). Activation of phosphatidylcholine cycle enzymes in human epithelial ovarian cancer cells. Cancer Res, 70, 2126-35. https://doi.org/10.1158/0008-5472.CAN-09-3833
  10. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  11. Ji Y, Gao S, Feng X, et al (2009). Calcium channel mechanism by which betaine promotes proliferation of lymphocytes in mice. Zhongguo Zhong Yao Za Zhi, 34, 1959-63 (in Chinese).
  12. Katz-Brull R, Seger D, Rivenson-Segal D, et al (2002). Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline-ether-phospholipid synthesis. Cancer Res, 62, 1966-70.
  13. Lai JC, Chou YJ, Huang N, et al (2013). Survival analysis of Stage IIA1 and IIA2 cervical cancer patients. Taiwan J Obstet Gynecol, 52, 33-8. https://doi.org/10.1016/j.tjog.2013.01.006
  14. Landry JJ, Pyl PT, Rausch T, et al (2013). The genomic and transcriptomic landscape of a HeLa cell line. G3 (Bethesda), 3, 1213-24. https://doi.org/10.1534/g3.113.005777
  15. Nagaraj N, Wisniewski JR, Geiger T, et al (2011). Deep proteome and transcriptome mapping of a human cancer cell line. Mol Syst Biol, 7, 548.
  16. Neumann B, Walter T, Heriche JK, et al (2010). Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Nature, 464, 721-7. https://doi.org/10.1038/nature08869
  17. Okazawa M, Mabuchi S, Isohashi F, et al (2013). Impact of the addition of concurrent chemotherapy to pelvic radiotherapy in surgically treated stage IB1-IIB cervical cancer patients with intermediate-risk or high-risk factors: a 13-year experience. Int J Gynecol Cancer, 23, 567-75. https://doi.org/10.1097/IGC.0b013e31828703fd
  18. Rupachandra S, Sarada DV (2014). Induction of apoptotic effects of antiproliferative protein from the seeds of Borreria hispida on lung cancer (A549) and cervical cancer (HeLa) cell lines. Biomed Res Int, 2014, 179836.
  19. Shao C, Sun W, Tan M, et al (2011). Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma. Clin Cancer Res, 17, 4320-30. https://doi.org/10.1158/1078-0432.CCR-10-2992
  20. Surh YJ (2003). Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer, 3, 768-80. https://doi.org/10.1038/nrc1189
  21. Tan AC, Konczak I, Sze DM, et al (2011). Molecular pathways for cancer chemoprevention by dietary phytochemicals. Nutr Cancer, 63, 495-505. https://doi.org/10.1080/01635581.2011.538953
  22. Ueland PM, Holm PI, Hustad S (2005). Betaine: a key modulator of one-carbon metabolism and homocysteine status. Clin Chem Lab Med, 43, 1069-75.
  23. Zhang LL, Wu J, Liu Q, et al (2014). MiR-886-5p Inhibition inhibits growth and induces apoptosis of MCF7 cells. Asian Pac J Cancer Prev, 15, 1511-5. https://doi.org/10.7314/APJCP.2014.15.4.1511

피인용 문헌

  1. Effects of niacin and betaine on bovine mammary and uterine cells exposed to thermal shock in vitro vol.100, pp.5, 2017, https://doi.org/10.3168/jds.2016-11876
  2. Stachydrine suppresses viability & migration of astrocytoma cells via CXCR4/ERK & CXCR4/Akt pathway activity vol.14, pp.15, 2018, https://doi.org/10.2217/fon-2017-0562
  3. The unusual reaction of alkylation of dicarboxylate phosphabetaines in alcohol media pp.1563-5325, 2019, https://doi.org/10.1080/10426507.2018.1547723