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

doi:10.1007/s11705-016-1574-2

Front. Chem. Sci. Eng.

2016, Vol. 10

Issue (3) : 383-388 https://doi.org/10.1007/s11705-016-1574-2

COMMUNICATION

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

Sunhui Chen¹,Qiuling Liang¹,Shuping Xie¹,Ergang Liu²,Zhili Yu¹,Lu Sun¹,Meong Cheol Shin³,Seung Jin Lee⁴,Huining He^1,^*(

),Victor C. Yang^1,^5,^6,^*(

)

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

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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.

Keywords curcumin sunitinib synergistic effect bovine serum albumin (BSA) nano-carriers

Corresponding Author(s): Huining He,Victor C. Yang

Just Accepted Date: 01 June 2016 Online First Date: 30 June 2016 Issue Date: 23 August 2016

Cite this article:

Sunhui Chen,Qiuling Liang,Shuping Xie, et al. Curcumin based combination therapy for anti-breast cancer: from in vitro drug screening to in vivo efficacy evaluation[J]. Front. Chem. Sci. Eng., 2016, 10(3): 383-388.

URL:

https://academic.hep.com.cn/fcse/EN/10.1007/s11705-016-1574-2
https://academic.hep.com.cn/fcse/EN/Y2016/V10/I3/383

Fig.1 In vitro screening of synergistic anti-tumor potency of four drugs when used in combination with curcumin. (a) Inhibition on the growth of MCF-7 cells exposed to curcumin formulated with other drugs at different ratios and drug regimens, and (b) viability of MCF-7 cells treated with drugs alone or in combination with curcumin. Unless otherwise stated, curcumin concentration was maintained at 27 mmol/L, and the drug ratio was referred to the molar ratio between the test drug versus CUR

Fig.2 Calculated combination index (CI) values of curcumin in combination with other drugs at different molar ratios (a) to (d) referred to the combination of curcumin with doxorubincin, erlotinib, sunitinib, and sorafenib, respectively. The meaning of CI was interpreted as: CI>1, antagonistic effect; CI= 1, additive effect; and CI<1, synergistic effect. The drug ratios were referred to the molar ratios between the test drug versus CUR

Fig.3 In vitro test of MCF-7 cells incubated with SUN, CUR, SUN+CUR or their encapsulated formulations in BSA nano-particles, respectively. It should be noted that SC represented the abbreviation of SUN+CUR

Fig.4 In vivo test after tumor treated with SUN, CUR, SUN+CUR or their encapsulated formulations in BSA nano-particles, respectively. The tumor volume was measured, and the symbols of ***, **, and * represented P <0.005, P <0.01, and P<0.05, respectively. The term of SC represented the abbreviation of SUN+CUR

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