Abstract
Recent studies indicate that β-elemene, a compound isolated from the Chinese herbal medicine Curcuma wenyujin, is capable of reversing tumor MDR, although the mechanism remains elusive. In this study, β-Elemene treatment markedly increased the intracellular accumulation of doxorubicin (DOX) and rhodamine 123 in both K562/DNR and SGC7901/ADR cells and significantly inhibited the expression of P-gp. Treatment of SGC7901/ADR cells with β-elemene led to downregulation of Akt phosphorylation and significant upregulation of the E3 ubiquitin ligases, c-Cbl and Cbl-b. Importantly, β-elemene significantly enhanced the anti-tumor activity of DOX in nude mice bearing SGC7901/ADR xenografts. Taken together, our results suggest that β-elemene may target P-gp-overexpressing leukemia and gastric cancer cells to enhance the efficacy of DOX treatment.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
-
Adaptor Proteins, Signal Transducing / metabolism*
-
Animals
-
Antineoplastic Agents / pharmacology
-
Antineoplastic Agents / therapeutic use*
-
Cell Line, Tumor
-
Curcuma / chemistry
-
Doxorubicin / pharmacology
-
Doxorubicin / therapeutic use*
-
Drug Resistance, Multiple / drug effects
-
Drug Resistance, Neoplasm / drug effects*
-
Gastric Mucosa / metabolism
-
Humans
-
Male
-
Mice
-
Mice, Inbred BALB C
-
Mice, Nude
-
Proto-Oncogene Proteins c-cbl / metabolism*
-
Sesquiterpenes / pharmacology
-
Sesquiterpenes / therapeutic use*
-
Signal Transduction / drug effects
-
Stomach / drug effects
-
Stomach Neoplasms / drug therapy*
-
Stomach Neoplasms / metabolism
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
Adaptor Proteins, Signal Transducing
-
Antineoplastic Agents
-
Sesquiterpenes
-
beta-elemene
-
Doxorubicin
-
CBLB protein, human
-
Proto-Oncogene Proteins c-cbl