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


OBJECTIVE
To evaluate the combinational anticancer effect of 23-hydroxybetulinic acid and doxorubicin in vitro and in vivo.


METHODS
The 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.


RESULTS
23-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.


CONCLUSIONS
These 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.
Zheng
Yuanting
Y
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
Zhou
Fang
F
Wu
Xiaolan
X
Wen
Xiaozhou
X
Li
Yannan
Y
Yan
Bei
B
Zhang
Jingwei
J
Hao
Gang
G
Ye
Wencai
W
Wang
Guangji
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000494:pharmacology; D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D031946:Pulsatilla / Q000737:chemistry*; D014315:Triterpenes; D015854:Up-Regulation / Q000187:drug effects
C468651:23-hydroxybetulinic acid; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014315:Triterpenes; D004317:Doxorubicin