Abstract
BackgroundNorcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study.MethodsTwo human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis.ResultsNCTD induced cell cycle arrest at G2/M phase in both cell lines. The early and late apoptosis was also observed. Further investigation indicated that NCTD suppressed not only the expression of the total EGFR and the phosphorylated EGFR but also the expression of the total c-Met and the phosphorylated c-Met in colon cancer cells. Moreover, EGFR expression could be mostly restored by co-treatment with MG132, a proteasome inhibitor. In addition, NCTD-induced cell death was comparable to that of the anti-cancer drug gefitinib, a tyrosine kinase inhibitor for EGFR, based on the immunoblot analysis of the expressed proteins after the drug treatment.ConclusionsNCTD might be a useful and inexpensive drug candidate to substitute for gefitinib to serve the treatment needs of cancer patients.
Highlights
Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment
The anti-cancer activity of NCTD relies on its ability in activation of the caspase signaling pathway that leads to apoptosis [7] accompanied with a decreased ratio of Bcl2/Bax [8, 9], the changes in the expression of cell cyclerelated proteins are co-related with cell cycle arrest [10], the interruption of DNA synthesis [11], inhibition of tumor invasion and metastasis [12, 13], MAPK activation, and protein kinase C pathway activation [14]
We demonstrated that NCTD suppressed the expressing level and phosphorylation of both c-Met and EGFR
Summary
Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. CTD has been identified as the active compound in Mylabris phalerata Pall with anti-tumor activity [1,2,3,4]. It causes severe side effects in the urinary system both in animals and in human [5]. The anti-cancer activity of NCTD relies on its ability in activation of the caspase signaling pathway that leads to apoptosis [7] accompanied with a decreased ratio of Bcl2/Bax [8, 9], the changes in the expression of cell cyclerelated proteins are co-related with cell cycle arrest [10], the interruption of DNA synthesis [11], inhibition of tumor invasion and metastasis [12, 13], MAPK activation, and protein kinase C pathway activation [14].
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