A synthetic cantharidin analog for the enhancement of doxorubicin suppression of stem cell-derived aggressive sarcoma.
Failure to cure many cancers once they are disseminated has been attributed to the presence of resistant cancer stem cells. Cantharidin, a natural compound isolated from the beetles and other insects has been traditionally used as anticancer agent, but limited by its significant toxicity. It has shown that cantharidin can force cancer cells prematurely into cell cycle and subsequently induce apoptotic cell death through the inhibition of protein phosphatase 2A (PP2A). In this study, we showed that a synthesized analog of cantharidin, LB1, with significant PP2A inhibition activity but without apparent toxicity, greatly enhanced the effectiveness of the standard anti-sarcoma chemotherapeutic agent, doxorubicin (DOX), in the xenograft growth inhibition and lung metastases prevention of an aggressive sarcoma derived from transformed mesenchymal stem cells in syngeneic rats. We report here on the possibility of, pharmacologic inhibition of PP2A with low toxicity cantharidin derivatives may be a useful strategy to enhance the effectiveness of DNA-damaged chemotherapeutic drugs against stem cell-derived cancer.
Zhang
Chao
C
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, 30 Gaotanyan Road, Chongqing 400038, China.
Peng
Yi
Y
Wang
Fengchao
F
Tan
Xu
X
Liu
Nan
N
Fan
Song
S
Wang
Dechun
D
Zhang
Lilong
L
Liu
Dengqun
D
Wang
Tao
T
Wang
Shaojun
S
Zhou
Yue
Y
Su
Yongping
Y
Cheng
Tianmin
T
Zhuang
Zhengping
Z
Shi
Chunmeng
C
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002193:Cantharidin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology*; D039902:Multipotent Stem Cells / Q000378:metabolism; D009362:Neoplasm Metastasis; D051381:Rats; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D015415:Biomarkers; D004317:Doxorubicin; D002193:Cantharidin