Open Access

A 20(S)‑protopanaxadiol derivative PPD12 reverses ABCB1‑mediated multidrug resistance with oral bioavailability and low toxicity

  • Authors:
    • Shunfeng Wei
    • Wantao Chen
    • Lihong Hu
    • Jinsong Pan
    • Xu Wang
  • View Affiliations

  • Published online on: August 21, 2018     https://doi.org/10.3892/ol.2018.9338
  • Pages: 5891-5899
  • Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The ATP‑binding cassette subfamily B member 1 (ABCB1) is a transporter that mediates multidrug resistance (MDR) against chemotherapy, which leads to decreased patient survival. To inhibit ABCB1 activity in MDR cancer cells, the authors previously designed and synthesized a derivative from 20(S)‑protopanaxadiol (PPD) PPD12 and verified its efficacy in ABCB1‑overexpressing cancer cells. In the present study, the reversal effect of PPD12 on MDR was further evaluated and its pharmacokinetics and toxicity in vitro and in vivo were investigated. Incubation with PPD12 may significantly ameliorate the drug resistance of KB/VCR cells in a short time and maintain its reversed MDR ability for increasing time periods. In assays on a series of CYP450 activities, PPD12 demonstrated slight inhibition effects on the majority of enzymes. The bioavailability of PPD12 was nearly 100% by oral administration in a mouse model. Single PPD12 oral gavage at either high doses or subchronic low doses, was well tolerated by the mice. In addition, PPD12 at the therapeutic dosage did not significantly increase the toxicity of the chemotherapeutic agent Adriamycin when mice received a combination of the two compounds. In conclusion, PPD12 represents a novel type of ABCB1 inhibitor that has significant bioactivity in terms of MDR, high oral bioavailability and low toxicity.
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November-2018
Volume 16 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Wei S, Chen W, Hu L, Pan J and Wang X: A 20(S)‑protopanaxadiol derivative PPD12 reverses ABCB1‑mediated multidrug resistance with oral bioavailability and low toxicity. Oncol Lett 16: 5891-5899, 2018
APA
Wei, S., Chen, W., Hu, L., Pan, J., & Wang, X. (2018). A 20(S)‑protopanaxadiol derivative PPD12 reverses ABCB1‑mediated multidrug resistance with oral bioavailability and low toxicity. Oncology Letters, 16, 5891-5899. https://doi.org/10.3892/ol.2018.9338
MLA
Wei, S., Chen, W., Hu, L., Pan, J., Wang, X."A 20(S)‑protopanaxadiol derivative PPD12 reverses ABCB1‑mediated multidrug resistance with oral bioavailability and low toxicity". Oncology Letters 16.5 (2018): 5891-5899.
Chicago
Wei, S., Chen, W., Hu, L., Pan, J., Wang, X."A 20(S)‑protopanaxadiol derivative PPD12 reverses ABCB1‑mediated multidrug resistance with oral bioavailability and low toxicity". Oncology Letters 16, no. 5 (2018): 5891-5899. https://doi.org/10.3892/ol.2018.9338