DOI QR코드

DOI QR Code

The Synergistic Anticancer Effect of Artesunate Combined with Allicin in Osteosarcoma Cell Line in Vitro and in Vivo

  • Jiang, Wei (Department of Orthopaedic, Wenling City Chinese Medicine Hospital) ;
  • Huang, Yong (Department of Orthopaedic, Wenling City Chinese Medicine Hospital) ;
  • Wang, Jing-Peng (Department of Orthopaedic, Wenling City Chinese Medicine Hospital) ;
  • Yu, Xiao-Yun (Department of Orthopaedic, Wenling City Chinese Medicine Hospital) ;
  • Zhang, Lin-Yi (Department of Orthopaedic, Wenling City Chinese Medicine Hospital)
  • 발행 : 2013.08.30

초록

Background: Artesunate, extracted from Artemisia annua, has been proven to have anti-cancer potential. Allicin, diallyl thiosulfinate, the main biologically active compound derived from garlic, is also of interest in cancer treatment research. This object of this report was to document synergistic effects of artesunate combined with allicin on osteosarcoma cell lines in vitro and in vivo. Methods: After treatment with artesunate and allicin at various concentrations, the viability of osteosarcoma cells was analyzed by MTT method, with assessment of invasion and motility, colony formation and apoptosis. Western Blotting was performed to determine the expression of caspase-3/9, and activity was also detected after drug treatment. Moreover, in a nude mouse model established with orthotopic xenograft tumors, tumor weight and volume were monitored after drug administration via the intraperitoneal (i.p.) route. Results: The viability of osteosarcoma cells in the combination group was significantly decreased in a concentration and time dependent manner; moreover, invasion, motility and colony formation ability were significantly suppressed and the apoptotic rate was significantly increased through caspase-3/9 expression and activity enhancement in the combination group. Furthermore, suppression of tumor growth was evident in vivo. Conclusion: Our results indicated that artesunate and allicin in combination exert synergistic effects on osteosarcoma cell proliferation and apoptosis.

키워드

참고문헌

  1. Arditti FD, Rabinkov A, Miron T, et al (2005). Apoptotic killing of B-chronic lymphocytic leukemia tumor cells by allicin generated in situ using a rituximab-alliinase conjugate. Mol Cancer Ther, 4, 325-31.
  2. Bacci G, Ferrari S, Bertoni F, et al (2000). Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the istituto ortopedico rizzoli according to the istituto ortopedico rizzoli/osteosarcoma-2 protocol: an updated report. J Clin Oncol, 18, 4016-27.
  3. Bachmeier B, Fichtner I, Killian PH, et al (2011). Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells. PLoS One, 6, e20550. https://doi.org/10.1371/journal.pone.0020550
  4. Bat-Chen W, Golan T, Peri I, Ludmer Z, Schwartz B (2010). Allicin purified from fresh garlic cloves induces apoptosis in colon cancer cells via Nrf2. Nutr Cancer, 62, 947-57. https://doi.org/10.1080/01635581.2010.509837
  5. Benassi MS, Chiechi A, Ponticelli F, et al (2007). Growth inhibition and sensitization to cisplatin by zoledronic acid in osteosarcoma cells. Cancer Lett, 250, 194-205. https://doi.org/10.1016/j.canlet.2006.10.004
  6. Berdelle N, Nikolova T, Quiros S, Efferth T, Kaina B (2011). Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells. Mol Cancer Ther, 10, 2224-33. https://doi.org/10.1158/1535-7163.MCT-11-0534
  7. Cha JH, Choi YJ, Cha SH, Choi CH, Cho WH (2012). Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway. Oncol Rep, 28, 41-8.
  8. Chano T, Mori K, Scotlandi K, et al (2004). Differentially expressed genes in multidrug resistant variants of U-2 OS human osteosarcoma cells. Oncol Rep, 11, 1257-63.
  9. Cheng R, Li C, Li C, et al (2013). The artemisinin derivative artesunate inhibits corneal neovascularization by inducing ROS-dependent apoptosis in vascular endothelial cells. Invest Ophthalmol Vis Sci, 54, 3400-9. https://doi.org/10.1167/iovs.12-11068
  10. Choeyprasert W, Natesirinilkul R, Charoenkwan P, Sittipreechacharn S (2013). Carboplatin and Doxorubicin in Treatment of Pediatric Osteosarcoma: A 9-year Single Institute Experience in the Northern Region of Thailand. Asian Pac J Cancer Prev, 14, 1101-6. https://doi.org/10.7314/APJCP.2013.14.2.1101
  11. Du JH, Zhang HD, Ma ZJ, Ji KM (2010). Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo. Cancer Chemother Pharmacol, 65, 895-902. https://doi.org/10.1007/s00280-009-1095-5
  12. Hamacher-Brady A, Stein HA, Turschner S, et al (2011). Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production. J Biol Chem, 286, 6587-601. https://doi.org/10.1074/jbc.M110.210047
  13. Hauben EI, Arends J, Vandenbroucke JP, et al (2003). Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma. Eur J Hum Genet, 11, 611-8. https://doi.org/10.1038/sj.ejhg.5201012
  14. Huang T, Gong WH, Li XC, et al (2012). Efficient killing effect of osteosarcoma cells by cinobufacini and cisplatin in combination. Asian Pac J Cancer Prev, 13, 2847-51. https://doi.org/10.7314/APJCP.2012.13.6.2847
  15. Jiang Z, Chai J, Chuang HH, et al (2012). Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells. Anticancer Drugs, 23, 606-13. https://doi.org/10.1097/CAD.0b013e328350e8ac
  16. Jin M, Shen X, Zhao C, et al (2013). In vivo study of effects of artesunate nanoliposomes on human hepatocellular carcinoma xenografts in nude mice. Drug Deliv, 20, 127-33. https://doi.org/10.3109/10717544.2013.801047
  17. Li LN, Zhang HD, Yuan SJ, et al (2007). Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/beta-catenin pathway. Int J Cancer, 121, 1360-5. https://doi.org/10.1002/ijc.22804
  18. Li PC, Lam E, Roos WP, et al (2008). Artesunate derived from traditional Chinese medicine induces DNA damage and repair. Cancer Res, 68, 4347-51. https://doi.org/10.1158/0008-5472.CAN-07-2970
  19. Li S, Xue F, Cheng Z, et al (2009). Effect of artesunate on inhibiting proliferation and inducing apoptosis of SP2/0 myeloma cells through affecting NFkappaB p65. Int J Hematol, 90, 513-21. https://doi.org/10.1007/s12185-009-0409-z
  20. Li T, Chen H, Yang Z, Liu XG, et al (2013). Evaluation of the immunosuppressive activity of artesunate in vitro and in vivo. Int Immunopharmacol, 16, 306-12. https://doi.org/10.1016/j.intimp.2013.03.011
  21. Louis XL, Murphy R, Thandapilly SJ, Yu L, Netticadan T (2012). Garlic extracts prevent oxidative stress, hypertrophy and apoptosis in cardiomyocytes: a role for nitric oxide and hydrogen sulfide. BMC Complement Altern Med, 12, 140. https://doi.org/10.1186/1472-6882-12-140
  22. Marina N, Gebhardt M, Teot L, Gorlick R (2004). Biology and therapeutic advances for pediatric osteosarcoma. Oncologist, 9, 422-41. https://doi.org/10.1634/theoncologist.9-4-422
  23. Meyers PA, Gorlick R, Heller G, et al (1998). Intensification of preoperative chemotherapy for osteogenic sarcoma: results of the Memorial Sloan-Kettering (T12) protocol. J Clin Oncol, 16, 2452-8.
  24. Miron T, Wilchek M, Shvidel L, Berrebi A, Arditti FD (2012). S-allyl derivatives of 6-mercaptopurine are highly potent drugs against human B-CLL through synergism between 6-mercaptopurine and allicin. Leuk Res, 36, 1536-40. https://doi.org/10.1016/j.leukres.2012.08.023
  25. Mota TC, Cardoso PC, Gomes LM, et al (2011). In vitro evaluation of the genotoxic and cytotoxic effects of artesunate, an antimalarial drug, in human lymphocytes. Environ Mol Mutagen, 52, 590-4. https://doi.org/10.1002/em.20659
  26. Oommen S, Anto RJ, Srinivas G, Karunagaran D (2004). Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. Eur J Pharmacol, 485, 97-103. https://doi.org/10.1016/j.ejphar.2003.11.059
  27. Padilla-Camberos E, Zaitseva G, Padilla C, Puebla AM (2010). Antitumoral activity of allicin in murine lymphoma L5178Y. Asian Pac J Cancer Prev, 11, 241-4.
  28. Park SY, Cho SJ, Kwon HC, et al (2005). Caspase-independent cell death by allicin in human epithelial carcinoma cells: involvement of PKA. Cancer Lett, 224, 123-32. https://doi.org/10.1016/j.canlet.2004.10.009
  29. Sertel S, Eichhorn T, Simon CH, et al (2010). Pharmacogenomic identification of c-Myc/Max-regulated genes associated with cytotoxicity of artesunate towards human colon, ovarian and lung cancer cell lines. Molecules, 15, 2886-910. https://doi.org/10.3390/molecules15042886
  30. Wang Z, Liu Z, Cao Z, Li L (2012). Allicin induces apoptosis in EL-4 cells in vitro by activation of expression of caspase-3 and -12 and up-regulation of the ratio of Bax/Bcl-2. Nat Prod Res, 26, 1033-7. https://doi.org/10.1080/14786419.2010.550894
  31. Youns M, Efferth T, Reichling J, et al (2009). Gene expression profiling identifies novel key players involved in the cytotoxic effect of Artesunate on pancreatic cancer cells. Biochem Pharmacol, 78, 273-83. https://doi.org/10.1016/j.bcp.2009.04.014
  32. Zhang W, Ha M, Gong Y, et al (2010). Allicin induces apoptosis in gastric cancer cells through activation of both extrinsic and intrinsic pathways. Oncol Rep, 24, 1585-92.
  33. Zhang ZM, Zhong N, Gao HQ, et al (2006). Inducing apoptosis and upregulation of Bax and Fas ligand expression by allicin in hepatocellular carcinoma in Balb/c nude mice. Chin Med J (Engl), 119, 422-5.
  34. Zhou C, Pan W, Wang XP, Chen TS (2012). Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells. J Cell Physiol, 227, 3778-86. https://doi.org/10.1002/jcp.24086

피인용 문헌

  1. Cytotoxic and Apoptotic Effects of Extracts of Artemisia ciniformis Krasch. & Popov ex Poljakov on K562 and HL-60 Cell Lines vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7055
  2. Gemcitabine for the Treatment of Patients with Osteosarcoma vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7159
  3. Inhibitory Effects of 3-Bromopyruvate on Human Gastric Cancer Implant Tumors in Nude Mice vol.15, pp.7, 2014, https://doi.org/10.7314/APJCP.2014.15.7.3175
  4. Anti-cancer Properties of a Sesquiterpene Lactone-bearing Fraction from Artemisia khorassanica vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.863
  5. Role of p38 MAPK activation and mitochondrial cytochrome-c release in allicin-induced apoptosis in SK-N-SH cells vol.27, pp.4, 2016, https://doi.org/10.1097/CAD.0000000000000340
  6. Hypoxic conditions increases H2S-induced ER stress in A2870 cells vol.414, pp.1-2, 2016, https://doi.org/10.1007/s11010-016-2659-4
  7. Artesunate attenuates unilateral ureteral obstruction-induced renal fibrosis by regulating the expressions of bone morphogenetic protein-7 and uterine sensitization-associated gene-1 in rats vol.48, pp.4, 2016, https://doi.org/10.1007/s11255-016-1232-0
  8. Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives vol.12, pp.2, 2017, https://doi.org/10.1371/journal.pone.0171840
  9. Artesunate Activates the Intrinsic Apoptosis of HCT116 Cells through the Suppression of Fatty Acid Synthesis and the NF-κB Pathway vol.22, pp.8, 2017, https://doi.org/10.3390/molecules22081272
  10. MicroRNA-26a induces osteosarcoma cell growth and metastasis via the Wnt/β-catenin pathway vol.11, pp.2, 2015, https://doi.org/10.3892/ol.2015.4073
  11. Chinese Herbal Medicine for Osteosarcoma in the Mouse: A Systematic Review and Meta-Analysis pp.1993-0402, 2018, https://doi.org/10.1007/s11655-018-2565-6