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SP‐101, a novel gefitinib derivative induces apoptosis and tumor inhibition
Author(s) -
Chao JuiI,
Wang SuPei,
Chen Chinpiao,
Yang JinnMoon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb100
Subject(s) - gefitinib , survivin , apoptosis , cancer research , epidermal growth factor receptor , lung cancer , poly adp ribose polymerase , chemistry , transfection , microbiology and biotechnology , biology , receptor , medicine , oncology , polymerase , biochemistry , dna , gene
Gefitinib, a tyrosine kinase inhibitor blocks epidermal growth factor receptor (EGFR) activity, has been used in lung cancer therapy. Here, we show a novel gefitinib derivative compound, named as SP‐101, exerts apoptosis and tumor inhibition in human lung cancer. SP‐101 was more effective in inducing the cell death than gefitinib and other derivatives in human lung cancer cell lines, including A549, H1299 and CL3. SP‐101 induced the caspase 3 activation and poly ADP‐ribose polymerase (PARP) protein cleavage. SP‐101 was more sensitive on the inhibition of survivin and cell growth than gefitinib. Transfection with a survivin‐expressed vector reduced the SP‐101‐induced cell death. More importantly, SP‐101 reduced the tumor size and survivin protein levels in the xenografted human lung tumors of nude mice. Besides, a molecular computational docking model shows that SP‐ 101 interacts with the ATP binding site of EGFR kinase domain. These results demonstrate that SP‐101 is a novel gefitinib derivative, which displays apoptosis induction and tumor suppression associated with the blockage of survivin.