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Curcumin based combination therapy for anti-breast cancer: from in vitro drug screening to in vivo efficacy evaluation

  • Sunhui Chen 1 ,
  • Qiuling Liang 1 ,
  • Shuping Xie 1 ,
  • Ergang Liu 2 ,
  • Zhili Yu 1 ,
  • Lu Sun 1 ,
  • Meong Cheol Shin 3 ,
  • Seung Jin Lee 4 ,
  • Huining He , 1 ,
  • Victor C. Yang , 1,5,6
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  • 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China
  • 2. Collaborative Innovation Center of Chemical Science and Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
  • 3. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinjudaero, Jinju, Gyeongnam 660-751, Republic of Korea
  • 4. Department of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Republic of Korea
  • 5. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, MI, USA
  • 6. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Republic of Korea

Received date: 08 Apr 2016

Accepted date: 10 May 2016

Published date: 23 Aug 2016

Copyright

2016 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

While drug resistance appears to be an inevitable problem of an increasing number of anticancer drugs in monotherapy, combination drug therapy has become a prosperous method to reduce the administered total drug dosages as well as overcome the drug resistance of carcinoma cells. Curcumin, considered to possess multi-faceted roles in cancer treatment according to its multiple anti-neoplastic mechanisms as a depressor of chemo-resistance, can significantly facilitate its anti-cancer functions and improve therapeutic effects via combination usage with a variety of other drugs with different reaction mechanisms. To explore this possibility, four anti-cancer chemotherapeutic agents that all possess a certain degree of drug resistance problems, including three tyrosine kinase inhibitors (erlotinib, sunitinib and sorafenib) that are acting on different cell pathways and a typical anticancer drug doxorubicin, were combined with curcumin individually to examine the synergistic anti-tumor effect both in vitro and in vivo. Results revealed that sunitinib combined with curcumin at the molar ratio of 0.46 yielded the most potent synergistic effect in vitro, and was therefore chosen for further animal evaluation. To further enhance the anti-cancer effect, bovine serum albumin (BSA) nanoparticles were utilized as a carrier to deliver the selected drug combination in situ. Preliminary in vivo findings confirmed our hypothesis of being able to maintain a similar injected drug ratio for prolonged time periods in tested animals by our approach, thereby maximizing the therapeutic potency yet minimizing the toxicity of these drugs. This work could open up a new avenue on combination drug therapy and realization the clinical utility of such drugs.

Cite this article

Sunhui Chen , Qiuling Liang , Shuping Xie , Ergang Liu , Zhili Yu , Lu Sun , Meong Cheol Shin , Seung Jin Lee , Huining He , Victor C. Yang . Curcumin based combination therapy for anti-breast cancer: from in vitro drug screening to in vivo efficacy evaluation[J]. Frontiers of Chemical Science and Engineering, 2016 , 10(3) : 383 -388 . DOI: 10.1007/s11705-016-1574-2

Acknowledgement

This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 81402856, A3 project-81361140344, and 21402143). Professors Lee SJ and Shin MC are participants from the Korean A3 Foresight Program sponsored by NRF. This research was also partially sponsored by Tianjin Municipal Science and Technology Commission (15JCYBJC28700 and 15JCQNJC13600). This research was partially supported by grants from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology Grants NRF-2015R1A6A3A01020598 and NRF-2015R1C1A1A02036781.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11705-016-1574-2 and is accessible for authorized users.
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