Browse > Article
http://dx.doi.org/10.7314/APJCP.2013.14.8.4615

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.8, 2013 , pp. 4615-4619 More about this Journal
Abstract
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.
Keywords
Artesunate; allicin; osteosarcoma cell line; apoptosis;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 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.   DOI   ScienceOn
2 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.   DOI
3 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.   DOI   ScienceOn
4 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.   DOI   ScienceOn
5 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.   DOI   ScienceOn
6 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.   DOI
7 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.   DOI   ScienceOn
8 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.   DOI   ScienceOn
9 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.   DOI   ScienceOn
10 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.   DOI
11 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.   DOI   ScienceOn
12 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.   DOI
13 Marina N, Gebhardt M, Teot L, Gorlick R (2004). Biology and therapeutic advances for pediatric osteosarcoma. Oncologist, 9, 422-41.   DOI   ScienceOn
14 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.
15 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.   DOI   ScienceOn
16 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.   DOI   ScienceOn
17 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.   DOI   ScienceOn
18 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.   DOI   ScienceOn
19 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.
20 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.   DOI   ScienceOn
21 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.   DOI   ScienceOn
22 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.   DOI   ScienceOn
23 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.
24 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.
25 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.   DOI   ScienceOn
26 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.   DOI   ScienceOn
27 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.
28 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.
29 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.   DOI
30 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.   DOI   ScienceOn
31 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.   DOI
32 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.
33 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.
34 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.   DOI