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. 2017 Aug 31;7:10298. doi: 10.1038/s41598-017-10972-0

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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CTRs effectively killed multidrug-resistant cancer cells, synergistically when combined with paclitaxel. (a,b) CTR-17 and CTR-20 effectively kill cells overexpressing MDR1 (a) or MRP1 (b). Note that the multidrug-resistant KB-C-2 and HEK293-MRP1 cells were developed from KB-3-1 cervical cancer cell line and HEK293 kidney cell line, respectively. Tax, Col and Vin denote paclitaxel, colchicine and vinblastine, respectively. (c,d) When combined with Tax, CTRs showed substantial synergistic cell-killing effects against KB-C-2 cells. The same concentrations were used for both single and combinational treatments. Combinational index (CI) < 1.0, CI = 1.0 and CI > 1.0 are synergistic, additive and antagonistic, respectively²⁷. (e) Both CTR-17 and CTR-20 effectively killed multidrug (paclitaxel)-resistant MDA-MB-231TaxR. The MDA-MB-231TaxR, which is 114 times more resistant to paclitaxel, was developed in house by culturing the MDA-MB-231 triple-negative metastatic breast cancer cell line in incrementally increased paclitaxel concentrations for over one-year period. (f) The combination of Tax and CTR-20 showed a strong synergistic effect against MDA-MB-231TaxR. The expression of MDR1 or MRP1 proteins in these cell lines are shown in Supplementary Fig. S7. Data presented are mean ± S.E.M value of triplicates of at least four independent experiments.