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P01.40. A new approach for quantifying chemosensitizing effects from herb-drug combinations: assessment of Tripterygium Wilfordii-Docetaxel in prostate cancer

Purpose

Resistance to cancer chemotherapy is a major problem. Herb-drug combinations can offer a new potential to overcome such resistance. To quantitatively assess chemosensitizing effects of herb-drug combinations (HDC), a new approach that takes into account both the chemosensitizing effect (CE) and “safety” considerations of the HDC is proposed and used in describing the cytotoxic activity of Tripterygium wilfordii-docetaxel (TW-Dtx) combination on prostate cancer cell lines.

Methods

The effect of two extracts of TW with Dtx on Dtx resistant PC3 and DU145 cell lines were compared. Cell viability (cytotoxicity) was determined using sulforhodamine B assay after incubation of the cell line. The IC50 of herb (H), drug (D) alone and in combination (IC50H, IC50D, and IC50CD respectively) in resistant cells were obtained. CE and chemosensitizing utility index (CUI) were calculated as: CE = IC50D IC50CD; CUI=CE (IC50H/ConH) whereas ConH is the H concentration in the combination.

Results

The values for CE (fold change), CUI (fold change), and IC50CD (nM) from TW extract A-Dtx treatment in resistant PC3 cells were 3.8 , 5.8, and 5.8, respectively versus 17.1, 22.0, and 1.5, respectively from TW extract B-Dtx treatment when low ConH relative to IC50H was used. The corresponding values from extract A versus B-Dtx treatment in resistant DU145 cells were >1.3, >4.5 and 75.3 versus >27.6, >55.2 and 3.63, respectively. However, CE values can dramatically increase with higher ConH.

Conclusion

Based on the above CE, CUI or ICCD values, TW extract B-Dtx appeared to be consistently superior to extract A-Dtx combination. However, assessment based on CE value alone may be misleading since it can change dramatically with ConH used. CUI together with IC50CD are preferred and may prove to be a useful practical tool for assessing chemosensitizing effect of other HDCs.

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Correspondence to Z Wang.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Wang, Z., Yeung, S., Tran, T. et al. P01.40. A new approach for quantifying chemosensitizing effects from herb-drug combinations: assessment of Tripterygium Wilfordii-Docetaxel in prostate cancer. BMC Complement Altern Med 12, P40 (2012). https://doi.org/10.1186/1472-6882-12-S1-P40

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Keywords

  • Public Health
  • Cancer Cell
  • Internal Medicine
  • Prostate Cancer
  • Cell Viability