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Enhanced Anti-tumor Efficacy of Aspirin Combined with Triptolide in Cervical Cancer Cells

  • Chen, Rong-Hui (Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University) ;
  • Tian, Yong-Jie (Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University)
  • Published : 2013.05.30

Abstract

Background: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. Methods: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. Results: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. Conclusion: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.

Keywords

Aspirin;triptolide;cervical cancer cells;combined treatment;synergy

References

  1. Borja-Cacho D, Yokoyama Y, Chugh RK, et al (2010). TRAIL and triptolide: an effective combination that induces apoptosis in pancreatic cancer cells. J Gastrointest Surg, 14, 252-60. https://doi.org/10.1007/s11605-009-1065-6
  2. Carter BZ, Mak DH, Schober WD, et al (2008). Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5. Blood, 111, 3742-50. https://doi.org/10.1182/blood-2007-05-091504
  3. Chen YW, Lin GJ, Chia WT, et al (2009). Triptolide exerts antitumor effect on oral cancer and KB cells in vitro and in vivo. Oral Oncol, 45, 562-8. https://doi.org/10.1016/j.oraloncology.2008.10.007
  4. Clawson KA, Borja-Cacho D, Antonoff MB, Saluja AK, Vickers SM (2010). Triptolide and TRAIL combination enhances apoptosis in cholangiocarcinoma. J Surg Res, 163, 244-9. https://doi.org/10.1016/j.jss.2010.03.067
  5. De Luna-Bertos E, Ramos-Torrecillas J, Garcia-Martinez O, Diaz-Rodriguez L, Ruiz C (2012). Effect of aspirin on cell growth of human MG-63 osteosarcoma line. ScientificWorldJournal, 2012, 834246.
  6. Dhillon PK, Kenfield SA, Stampfer MJ, Giovannucci EL, Chan JM (2012). Aspirin use after a prostate cancer diagnosis and cancer survival in a prospective cohort. Cancer Prev Res (Phila), 5, 1223-8. https://doi.org/10.1158/1940-6207.CAPR-12-0171
  7. El Kebir D, Filep JG (2013). Modulation of Neutrophil Apoptosis and the Resolution of Inflammation through $\beta2$ Integrins. Front Immunol, 4, 60.
  8. Gadducci A, Barsotti C, Cosio S, Domenici L, Riccardo Genazzani A (2011). Smoking habit, immune suppression, oral contraceptive use, and hormone replacement therapy use and cervical carcinogenesis: a review of the literature. Gynecol Endocrinol, 27, 597-604. https://doi.org/10.3109/09513590.2011.558953
  9. Green JA, Kirwan JM, Tierney JF, et al (2001). Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and metaanalysis. Lancet, 358, 781-6. https://doi.org/10.1016/S0140-6736(01)05965-7
  10. Hsieh CC, Hernandez-Ledesma B, de Lumen BO (2010). Lunasin, a novel seed peptide, sensitizes human breast cancer MDAMB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact, 186, 127-34. https://doi.org/10.1016/j.cbi.2010.04.027
  11. Huang M, Zhang H, Liu T, et al (2013). Triptolide inhibits MDM2 and induces apoptosis in acute lymphoblastic leukemia cells through a p53-independent pathway. Mol Cancer Ther, 12, 184-94. https://doi.org/10.1158/1535-7163.MCT-12-0425
  12. 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
  13. Kodela R, Chattopadhyay M, Goswami S, et al (2013). Positional isomers of aspirin are equally potent in inhibiting colon cancer cell growth: differences in mode of cyclooxygenase inhibition. J Pharmacol Exp Ther, 345, 85-94. https://doi.org/10.1124/jpet.112.201970
  14. Lea JS, Lin KY (2012). Cervical cancer. Obstet Gynecol Clin North Am, 39, 233-53. https://doi.org/10.1016/j.ogc.2012.02.008
  15. Li H, Hui L, Xu W, et al (2012). Triptolide modulates the sensitivity of K562/A02 cells to adriamycin by regulating miR-21 expression. Pharm Biol, 50, 1233-40. https://doi.org/10.3109/13880209.2012.665931
  16. Lu L, Kanwar J, Schmitt S, et al (2011). Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vine'. Anticancer Res, 31, 1-10.
  17. Marrazzo JM, Koutsky LA, Kiviat NB, Kuypers JM, Stine K (2001). Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women. Am J Public Health, 91, 947-52. https://doi.org/10.2105/AJPH.91.6.947
  18. Messina ME Jr, Halaby R (2011). Does triptolide induce lysosomal-mediated apoptosis in human breast cancer cells? Med Hypotheses, 77, 91-3. https://doi.org/10.1016/j.mehy.2011.03.034
  19. Ou YQ, Zhu Wb, Li Y, et al (2010). Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity. Acta Pharmacol Sin, 31, 73-80. https://doi.org/10.1038/aps.2009.172
  20. Paavonen J (2007). Human papillomavirus infection and the development of cervical cancer and related genital neoplasias. Int J Infect Dis, 11, S3-9. https://doi.org/10.1016/S1201-9712(07)60015-0
  21. Park IS, Jo JR, Hong H, et al (2010). Aspirin induces apoptosis in YD-8 human oral squamous carcinoma cells through activation of caspases, down-regulation of Mcl-1, and inactivation of ERK-1/2 and AKT. Toxicol In Vitro, 24, 713-20. https://doi.org/10.1016/j.tiv.2010.01.010
  22. Pazhang Y, Ahmadian S, Javadifar N, Shafiezadeh M (2012). COX-2 and survivin reduction may play a role in berberineinduced apoptosis in human ductal breast epithelial tumor cell line. Tumour Biol, 33, 207-14. https://doi.org/10.1007/s13277-011-0263-5
  23. Pectasides D, Kamposioras K, Papaxoinis G, Pectasides E (2008). Chemotherapy for recurrent cervical cancer. Cancer Treat Rev, 34, 603-13. https://doi.org/10.1016/j.ctrv.2008.05.006
  24. Singh A, Rathaur S (2010). Combination of DEC plus aspirin induced mitochondrial mediated apoptosis in filarial parasite Setaria cervi. Biochimie, 92, 894-900. https://doi.org/10.1016/j.biochi.2010.03.018
  25. Tan BJ, Chiu GN (2013). Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis. Int J Oncol, 42, 1605-12.
  26. Westfall SD, Nilsson EE, Skinner MK (2008). Role of triptolide as an adjunct chemotherapy for ovarian cancer. Chemotherapy, 54, 67-76. https://doi.org/10.1159/000112419
  27. Xiaoxin M, Yingnan J, Yanxia L, et al (2009). Experimental research on the depressant effect of aspirin on Ishikawa adenocarcinoma endometrium cell growth. Int J Gynecol Cancer, 19, 1182-5. https://doi.org/10.1111/IGC.0b013e3181a12f91
  28. Yan F, He Q, Hu X, et al (2013). Direct regulation of caspase‑3 by the transcription factor AP‑$2\alpha$ is involved in aspirin‑induced apoptosis in MDA‑MB‑453 breast cancer cells. Mol Med Rep, 7, 909-14.
  29. Yang M, Huang J, Pan HZ, Jin J (2008). Triptolide overcomes dexamethasone resistance and enhanced PS-341-induced apoptosis via PI3k/Akt/NF-kappaB pathways in human multiple myeloma cells. Int J Mol Med, 22, 489-96.
  30. Zhao F, Chen Y, Zeng L, et al (2010). Role of triptolide in cell proliferation, cell cycle arrest, apoptosis and histone methylation in multiple myeloma U266 cells. Eur J Pharmacol, 646, 1-11. https://doi.org/10.1016/j.ejphar.2010.05.034
  31. Zhu W, Li J, Wu S, et al (2012). Triptolide cooperates with Cisplatin to induce apoptosis in gemcitabine-resistant pancreatic cancer. Pancreas, 41, 1029-38. https://doi.org/10.1097/MPA.0b013e31824abdc0
  32. Zhu W, Hu H, Qiu P, Yan G (2009). Triptolide induces apoptosis in human anaplastic thyroid carcinoma cells by a p53-independent but NF-kappaB-related mechanism. Oncol Rep, 22, 1397-401.

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