Norcantharidin Inhibits cell growth by suppressing the expression and phosphorylation of both EGFR and c-Met in human colon cancer cells

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.

Anti-EGFR-Coated Gold Nanoparticles In Vitro Carry 5-Fluorouracil to Colorectal Cancer Cells

“…This difference may have happened due to significantly higher EGFR expression on the surface of HT-29 cells than on the surface of HCT-116 cells. In fact, HT-29 cells are poorly sensitive to anti-EGFR, whereas HCT-116 cells are resistant to this antibody, a fact that reinforces the specificity and efficiency of the selected antibody to drive particles towards target cells [33], as well as the positive effect of it conjugation on AuNP.…”

Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells

“…Previous studies have reported that NCTD is a synthetic anticancer compound that inhibits c‐Met in human colon cancers . Increasing evidence has demonstrated that overactive c‐Met signaling is a key driver of tumor progression .…”

“…Previous studies have reported that NCTD is a synthetic anticancer compound that inhibits c-Met in human colon cancers. 11 Increasing evidence has demonstrated that overactive c-Met signaling is a key driver of tumor progression. 12 We next explored the effects of NCTD on the c-Met signaling pathway by examining the expression of c-Met and phosphorylated c-Met (p-c-Met) by western blotting.…”

Analysis of contribution of protein phosphorylation in the development of the diseases

“…Разработаны и испытываются множество малых ингибиторных молекул, которые нацелены на АТР связывающую область доменов тирозинкиназных рецепторов и препятствуют автофосфорилированию. Например, ингибиторы EGFR, такие как гефитиниб, эрлотиниб и другие, продемонстрировали свою эффективность для лечения EGFR-зависимых немелкоклеточного рака лёгкого [42], рака молочной железы [43,44], колоректального рака [45], глиобластомы [46,47]. Ингибиторы сигнальных каскадов PDGFR показали положительный эффект в клинических испытаниях при лечении миелоидного лейкоза и желудочно-кишечных стромальных опухолей [48], менингиомы [49].…”