Asian Pacific Journal of Cancer Prevention

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

DOI QR Code

Radio-Sensitization by Piper longumine of Human Breast Adenoma MDA-MB-231 Cells in Vitro

  • Yao, Jian-Xin (Department of Medical Imaging, Nanjing Health college of Jiangsu Union Technical Institute) ;
  • Yao, Zhi-Feng (Department of Radiation Oncology, The Second Affiliated Hospital of Nanjing Medical University) ;
  • Li, Zhan-Feng (Department of Medical Imaging, Nanjing Health college of Jiangsu Union Technical Institute) ;
  • Liu, Yong-Biao (Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University)
  • Published : 2014.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Materials and Methods: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose ($D_0$), quasi-threshold dose ($D_q$) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM). Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. Results: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Conclusions: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA-MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

Keywords

References

  1. Bauer KR, Brown M, Cress RD, et al (2007). Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer, 109, 1721-28. https://doi.org/10.1002/cncr.22618
  2. Bezerra FCF, Filho JTS, de Oliveira Souza LE (2007). Piplartine, an amide alkaloid from Piper tuberculatum, presents anxiolytic and antidepressant effects in mice. Phytomedicine, 14, 605-12. https://doi.org/10.1016/j.phymed.2006.12.015
  3. Bezerra DP, Militao GC, de Castro FO, et al (2007). Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways. Toxicol In Vitro, 21, 1-8. https://doi.org/10.1016/j.tiv.2006.07.007
  4. Corvo R, Antognoni P, Sanguineti G (2001). Biological predictors of response to radiotherapy in head and neck cancer: recent advances and emerging perspectives. Tumor, 87, 355-63.
  5. Dent R, Trudeau M, Priitchard KI, et al (2007). Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res, 13, 4429-34. https://doi.org/10.1158/1078-0432.CCR-06-3045
  6. Durackova Z (2010). Some current insights into oxidative stress. Physiol Res, 59, 459-69.
  7. de Moraes J, Nascimento C, Lopes POMV, et al (2011). Schistosoma mansoni: In vitro schistosomicidal activity of piplartine. Exp Parasitol, 127, 357-64. https://doi.org/10.1016/j.exppara.2010.08.021
  8. Fontenele JB, Leal LK, Silveira ER, et al (2009). Antiplatelet effects of piplartine, an alkaloid isolated from Piper tuberculatum: possible involvement of cyclooxygenase blockade and antioxidant activity. Pharm Pharmacol, 61, 511-5. https://doi.org/10.1211/jpp.61.04.0014
  9. Grant CM (2001). Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Mol Microbiol, 39, 533-41. https://doi.org/10.1046/j.1365-2958.2001.02283.x
  10. Hara T, Omura-Minamisawa M, Chao C et al (2005). Bcl-2 inhibitors potentiate the cytotoxic effects of radiation in Bcl-2 over-expressing radio-resistant tumor cells. Int J Radiat Oncol Biol Phys, 61, 517-28. https://doi.org/10.1016/j.ijrobp.2004.10.008
  11. Jabs T (1999). Reactive oxygen intermediates asmediators of programmed cell death in plants and animals. Biochem Pharmacol, 57, 231-45. https://doi.org/10.1016/S0006-2952(98)00227-5
  12. Ji Z, Tang QJ, Zhang JS, et al (2011). Oridonin-induced apoptosis in SW620 human colorectal adenocarcinoma cells. Oncol Lett, 2, 1303-7. https://doi.org/10.3892/ol.2011.408
  13. Kong EH, Kim YJ, Kim YJ, et al (2008). Piplartine induces caspase-mediated apoptosis in PC-3 human prostate cancer cells. Oncol Rep, 20, 785-92.
  14. Lee SE, Park BS, Bayman P, et al (2007). Suppression of ochratoxin biosynthesis by naturally occurring alkaloids. Food Addit Contam, 24, 391-7. https://doi.org/10.1080/02652030601053147
  15. Meyn RE, Stephens LC, Ang KK, et al (1993). Heterogeneity in the development of apoptosis in irradiated routine tumors of different histologies. Int J Radiat Biol Phys, 64, 583. https://doi.org/10.1080/09553009314551801
  16. Mrtrailler-Ruchonnet I, Pagano A, Carnesecchi, et al (2007). Bcl-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria-dependent pathway. Free Radic Biol Med, 42, 1062-74. https://doi.org/10.1016/j.freeradbiomed.2007.01.008
  17. Meng FM, Yang JB, Yang CH, et al (2012). Vitexicarpin induces apoptosis in human prostate carcinoma PC-3 cells through G2/M phase arrest. Asian Pac J Cancer Prev, 13, 6369-74. https://doi.org/10.7314/APJCP.2012.13.12.6369
  18. Pompella A, Visvikis A, Paolicchi A et al (2003). The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol, 66, 1499-503. https://doi.org/10.1016/S0006-2952(03)00504-5
  19. Park BS, Son DJ, Park YH, et al (2007). Antiplatelet effects of acidamides isolated from the fruits of Piper longum L. Phytomedicine, 14, 853-5. https://doi.org/10.1016/j.phymed.2007.06.011
  20. Rodrigues RV, Lanznaster D, Longhi Balbinot DT, et al (2009). Antinociceptive effect of crude extract, fractions and three alkaloids obtained from fruits of Piper tuberculatum. Biol Pharm Bull, 32, 1809-12. https://doi.org/10.1248/bpb.32.1809
  21. Raj L, IdeT, Gurkar AU, et al (2011). Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature, 475, 231-4. https://doi.org/10.1038/nature10167
  22. Sekine I, Shimizu C, Nishio K, et al (2009). A literature review of molecular markers predictive of clinical response to cytotoxic chemotherapy in patients with breast cancer. Int J Clin Oncol, 14, 112-9. https://doi.org/10.1007/s10147-008-0813-z
  23. Song HY, Deng XH, Yuan GY, et al (2014). Expression of bcl-2 and p53 in induction of esophageal cancer cell apoptosis by ECRG2 in combination with cisplatin. Asian Pac J Cancer Prev, 15, 1397-401. https://doi.org/10.7314/APJCP.2014.15.3.1397
  24. Ueda S, Masutani H, Nakamura H, et al (2002). Redox control of cell death. Antioxid Redox Signal, 4, 405-14. https://doi.org/10.1089/15230860260196209
  25. Valko M, Leibfritz D, Moncol J, et al (2007). Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol, 39, 44-84. https://doi.org/10.1016/j.biocel.2006.07.001
  26. Yu J, Zhou XM, He XS, et al (2011). Curcumin induces apoptosis involving bax/bcl-2 in human hepatoma SMMC-7721 cells. Asian Pac J Cancer Prev, 12, 1925-9.
  27. Yao ZF, Yao JX, He X, et al (2013). Experimental study of piperlongumine inducing apoptosis of human breast adenoma MDA-MB-231 cells. Chinese-German J Clin Oncol, 12, 319-25. https://doi.org/10.1007/s10330-013-1144-8
  28. Yao ZF, Yao JX, Liu YB (2013). Antitumor effect of piplartine and its mechanism. Int J Oncol, 40, 259-63.
  29. Yao JX, Yao ZF, Liu YB (2013). Radiation enhancement of cetuximab on human breast adenoma MDA-MB-231 cells line. Chin J Cancer Prev Treat, 20, 898-903.
  30. Zou W, Liu X, Yue P, et al (2004). c-Jun NH2-terminal kinase-mediated up-regulation of death receptor 5 contributes to induction of apoptosis by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate in human lung cancer cells. Cancer Res, 64, 7570-8. https://doi.org/10.1158/0008-5472.CAN-04-1238
  31. Zhang YX, Guzalnur A, Jun W, et al (2014). Mechanisms of Hela cell apoptosis induced by abnormals avda munziq total phenolics combined with chemotherapeutic agents. Asian Pac J Cancer Prev, 15, 743-7. https://doi.org/10.7314/APJCP.2014.15.2.743

Cited by

  1. Dealing Naturally with Stumbling Blocks on Highways and Byways of TRAIL Induced Signaling vol.15, pp.19, 2014, https://doi.org/10.7314/APJCP.2014.15.19.8041
  2. Piperlongumine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane vol.6, pp.10, 2014, https://doi.org/10.3390/toxins6102975
  3. Radiosensitization Effects of a Zataria multiflora Extract on Human Glioblastoma Cells vol.16, pp.16, 2015, https://doi.org/10.7314/APJCP.2015.16.16.7285
  4. MicroRNA-190b confers radio-sensitivity through negative regulation of Bcl-2 in gastric cancer cells vol.39, pp.4, 2017, https://doi.org/10.1007/s10529-016-2273-2
  5. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence vol.17, pp.4, 2016, https://doi.org/10.3390/ijms17040616
  6. Targeted Inhibition of Glutamine-Dependent Glutathione Metabolism Overcomes Death Resistance Induced by Chronic Cycling Hypoxia vol.25, pp.2, 2016, https://doi.org/10.1089/ars.2015.6589
  7. Hypoxic Radioresistance: Can ROS Be the Key to Overcome It? vol.11, pp.1, 2019, https://doi.org/10.3390/cancers11010112