H6, a novel hederagenin derivative, reverses multidrug resistance in vitro and in vivo

Yanting Yang, Daokun Guan, Lei Lei, Jing Lu, Jia Qi Liu, Gangqiang Yang, Chunhong Yan, Rong Zhai, Jingwei Tian, Yi Bi, Fenghua Fu, Hongbo Wang

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Multidrug resistance (MDR) is a serious obstacle encountered in cancer treatment, in which the overexpression of P-glycoprotein (P-gp) plays an important role. Here, a novel α-hederagenin derivative, designated H6, was designed, synthesized and evaluated for its ability to reverse MDR. Our results showed that H6 could sensitize KBV and MCF7/T cells to paclitaxel and vincristine. Meanwhile, H6 could increase both rhodamine 123 and paclitaxel accumulation in MDR cells without affecting the expression of P-gp. Interestingly, siRNA knockdown of MDR1 further sensitized the cytotoxic activity of paclitaxel when co-administrated with H6. In addition, H6 could directly stimulate P-gp ATPase activity in vitro. Importantly, H6 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors in nude mice. Finally, H6 showed high binding affinity with P-gp with a high docking score. Overall, we show H6 is a novel and potent MDR reversal agent, which has the potential to be administered in combination with conventional anticancer drugs.

Original languageEnglish (US)
Pages (from-to)98-105
Number of pages8
JournalToxicology and Applied Pharmacology
StatePublished - Feb 15 2018


  • H6
  • Molecular docking
  • Multidrug resistance
  • P-glycoprotein
  • α-Hederagenin

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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