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Apoptosis induced by chamaejasmine in human osteosarcoma cells through p53 pathway

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Tumor Biology

Abstract

Osteosarcoma cancer is one of the most lethal malignancies, and there is no effective preventive measure to date. Chamaejasmine is the major ingredient in Stellera chamaejasme L. Except its potent pain-relieving efficacy as reported, chamaejasmine also exerted its anti-tumor activity in several tumor models. Here, we reported that chamaejasmine had a profound anti-proliferative effect on human osteosarcoma cells in a concentration-dependent and time-dependent manner, which was associated with an increase of p21 and bax and a decrease of bcl-2 and consequently increased caspase-3 activity. The main mechanism of anti-tumor potency was mainly attributed to the induction of p53. Chamaejasmine hugely elevated the expression of p53. The results of p53 shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to chamaejasmine, implicating the important role of p53 played in chamaejasmine’s anti-tumor activity. In conclusion, results showed chamaejasmine induced apoptosis in MG63 cells and could be a candidate drug for osteosarcoma cancer chemoprevention.

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References

  1. Hegyi M, Semsei AF, Jakab Z, Antal I, Kiss J, Szendroi M, et al. Good prognosis of localized osteosarcoma in young patients treated with limb-salvage surgery and chemotherapy. Pediatr Blood Cancer. 2011;57(3):415–22.

    Article  PubMed  Google Scholar 

  2. Jaffe N. Osteosarcoma: review of the past, impact on the future. Cancer Treat Res. 2009;152:239–62.

    Article  PubMed  Google Scholar 

  3. Ferguson WS, Goorin AM. Current treatment of osteosarcoma. Cancer Invest. 2001;19:292–315.

    Article  CAS  PubMed  Google Scholar 

  4. Bacci G, Lari S. Adjuvant and neoadjuvant chemotherapy in osteosarcoma. Chir Organi Mov. 2001;86:253–68.

    CAS  PubMed  Google Scholar 

  5. Biermann JS, Baker LH. The future of sarcoma treatment. Semin Oncol. 1997;24:592–7.

    CAS  PubMed  Google Scholar 

  6. La Quaglia MP. Osteosarcoma. Specific tumor management and results. Chest Surg Clin N Am. 1998;8:77–95.

    PubMed  Google Scholar 

  7. Ma QG, Liu WZ, Wu HM, Zhou TX, Qin GW. Phytochemistry. 1997;44:663–6.

    Article  CAS  Google Scholar 

  8. Che CT, Ma QG, Qin GW, Williams ID, Wu HM. Phytochemistry. 1999;52:117–21.

    Article  CAS  Google Scholar 

  9. Lee SH, Tanaka T, Nonaka GI, Nishioka I, Zhang B. Phytochemistry. 1991;30:1251–3.

    Article  CAS  Google Scholar 

  10. Tu SJ, Wang P, Wei A. Chin J Integr Trad West Med. 1984;4:46–7.

    Google Scholar 

  11. Marina N, Gebhardt M, Teot L, Gorlick R. Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 2004;9:422–41.

    Article  PubMed  Google Scholar 

  12. Papagelopoulos PJ, Galanis EC, Vlastou C, Nikiforidis PA, Vlamis JA, Boscainos PJ, et al. Current concepts in the evaluation and treatment of osteosarcoma. Orthopedics. 2000;23:858–67.

    CAS  PubMed  Google Scholar 

  13. Yang C, Ji D, Weinstein EJ, Choy E, Hornicek FJ, Wood KB, et al. The kinase Mirk is a potential therapeutic target in osteosarcoma. Carcinogenesis. 2010;31:552–8.

    Article  CAS  PubMed  Google Scholar 

  14. Los M, De Craen MV, Penning LC, Schenk H, Westendorp M, Baeuerle PA, et al. Schulze-Osthoff, requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature. 1995;375:81–3.

    Article  CAS  PubMed  Google Scholar 

  15. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 1995;376(6535):37–43.

    Article  CAS  PubMed  Google Scholar 

  16. Petros AM, Olejniczak ET, Fesik SW. Structural biology of the Bcl-2 family of proteins. Biochim Biophys Acta. 2004;1644:83–94.

    Article  CAS  PubMed  Google Scholar 

  17. Enneking WF, Springfield DS. Osteosarcoma. Orthop Clin North Am. 1977;8:785–803.

    CAS  PubMed  Google Scholar 

  18. Delling G. Diagnosis of bone tumors. Verh Dtsch Ges Pathol. 1998;82:121–32.

    CAS  PubMed  Google Scholar 

  19. Federman N, Bernthal N, Eilber FC, Tap WD. The multidisciplinary management of osteosarcoma. Curr Treat Options Oncol. 2009;10:82–93.

    Article  PubMed  Google Scholar 

  20. Wang Y, Zhao Y, Liu Y, Tian L, Jin D. Chamaejasmine inactivates Akt to trigger apoptosis in human HEp-2 larynx carcinoma cells. Molecules. 2011;16:8152–64.

    Article  CAS  PubMed  Google Scholar 

  21. Fang W, Liu S, Nie Y. Anticancer activity of chamaejasmine: effect on tubulin protein. Molecules. 2011;16:6243–54.

    Article  CAS  PubMed  Google Scholar 

  22. Cooper JD, Michaelidis TM, Tzimagiorgis GZ, Sendtner M, Meyer M, Thoenen H. Cholinergic neuron-specific overexpression of Bax in ChAT Bax transgenic mice. Soc Neurosci Abstr. 1996;22:570.

    Google Scholar 

  23. Kobayashi T, Ruan S, Clodi K, Kliche KO, Shiku H, Andreeff M, et al. Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis induced by selective chemotherapeutic agents. Oncogene. 1998;16:1587–91.

    Article  CAS  PubMed  Google Scholar 

  24. Cmielová J, Rezáčová M. p21Cip1/Waf1 protein and its function based on a subcellular localization. J Cell Biochem. 2011;112(12):3502–6.

    Article  PubMed  Google Scholar 

  25. Liu WK, Cheung FW, Liu BP, Li C, Ye W, Che CT. Involvement of p21 and FasL in induction of cell cycle arrest and apoptosis by neochamaejasmin a in human prostate LNCaP cancer cells. J Nat Prod. 2008;71:842–6.

    Article  CAS  PubMed  Google Scholar 

  26. Zhang T, Yu H, Dong G, Cai L, Bai Y. Chamaejasmine arrests cell cycle, induces apoptosis and inhibits nuclear NF-κB translocation in the human breast cancer cell line MDA-MB-231. Molecules. 2013;18:845–58.

    Article  CAS  PubMed  Google Scholar 

  27. Yu H, Zhang T, Cai L, Qu Y, Hu S, Dong G, et al. Chamaejasmine induces apoptosis in human lung adenocarcinoma A549 cells through a Ros-mediated mitochondrial pathway. Molecules. 2011;16:8165–80.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Xiaoping Ren.

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Yang, D., Wang, P. & Ren, X. Apoptosis induced by chamaejasmine in human osteosarcoma cells through p53 pathway. Tumor Biol. 36, 5433–5439 (2015). https://doi.org/10.1007/s13277-015-3209-5

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  • DOI: https://doi.org/10.1007/s13277-015-3209-5

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