23-Hydroxybetulinic acid from Pulsatilla chinensis (Bunge) Regel synergizes the antitumor activities of doxorubicin in vitro and in vivo

Ethnopharmacological revelancePulsatilla chinensis (Bunge)Regel has been used as adjuvant in chemotherapy in traditional Chinese medicine. 23-Hydroxybetulinic acid, an isolated pentacyclic triterpene, is the major active constituent of Pulsatilla chinensis (Bunge) Regel.Aim of this studyTo evaluate the combinational anticancer effect of 23-hydroxybetulinic acid and doxorubicin in vitro and in vivo.Materials and methodsThe effect of combination treatment with 23-hydroxybetulinic acid and doxorubicin was evaluated with a quantitative combination index method based on the median-effect analysis in various cancer cell lines. And in vivo efficacy of combination chemotherapy was also evaluated using ICR mice bearing sarcoma 180 carcinoma tumors.Results23-Hydroxybetulinic acid showed a synergistic cytotoxic effect on multiple cancer cell lines by combined use with doxorubicin. In vivo studies further demonstrated that co-administration of 23-HBA significantly improved the sensitivity of the tumor to doxorubicin through increasing intra-tumor doxorubicin concentration and inhibiting doxorubicin-induced up-regulation of P-gp in tumor.ConclusionThese results suggest that the combined therapy with 23-hydroxybetulinic acid and doxorubicin may be a new promising strategy to promote the clinical chemotherapy, which needs further verification.

Figure optionsDownload as PowerPoint slide