Homoharringtonine

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Homoharringtonine

CAS No. : 26833-87-4

MCE 国际站：Homoharringtonine

产品活性：Homoharringtonine (Omacetaxine mepesuccinate;HHT) 是具有抗肿瘤特性的细胞毒性生物碱，其通过抑制翻译延长来起作用。

研究领域：JAK/STAT Signaling  |  Stem Cell/Wnt

作用靶点：STAT

In Vitro: Homoharringtonine inhibits IL-6-induced STAT3 phosphorylation in a dose- and time-dependent manner. Homoharringtonine (HHT) inhibits cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. The cytotoxicity of Homoharringtonine on human NSCLC cell lines is investigated, A549 (wild type EGFR) and NCI-H1975 (H1975, mutant EGFR with L858R and T790M), Gefitinib is used as a control. By MTT assay, Homoharringtonine has moderate cytotoxicity to A549 with an IC₅₀ of 3.7 μM and H1975 cells are more sensitive to Homoharringtonine with an IC₅₀ of 0.7 μM. Homoharringtonine inhibits the cell proliferation and growth of A549 cells and H1975 cells in a time- and dose-dependent manner through MTT assay. By trypan blue exclusion assay, Homoharringtonine rapidly reduces viable A549 and H1975 cells in a dose- and time-dependent manner. Homoharringtonine significantly inhibits the clonogenic ability of A549 and H1975 cells.

In Vivo: Homoharringtonine (10 mg/kg) efficiently represses tumor growth compared to vehicle control or Gefitinib (P<0.05). Additionally, Homoharringtonine (HHT) treatment does not reduce the mice body weight, which suggests that Homoharringtonine has no apparent side effect. All the mice are euthanized, the tumors are isolated and imaged and the tumor sample cells are harvested to extract protein for determination if Homoharringtonine inhibits STAT3 phosphorylation via western blot. The level of STAT3 phosphorylation and MCL1 from Homoharringtonine treatment group is significantly decreased compared to vehicle control or Gefitinib treatment. Meanwhile, consistant with the results in the above, AKT1/2/3 and ERK1/2 phosphorylation is not inhibited with Homoharringtonine treatment. To further examine the STAT3 phosphorylation in the xenograft tumor samples with different treatments, the tumor samples are frozen and cutted into 10 μm sections for fluorescent immunohistochemistry. Homoharringtonine treatment inhibits STAT3 phosphorylation compared to vehicle control or Gefitinib treatment.

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