Browsing by Author "Wang, Su-Pei"

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A novel EGFR inhibitor SP101 blocks survivin and tumor growth in the human non-small cell lung carcinoma
(2015-04-01)
Chao, Jui-I
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Wang, Su-Pei
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Wu, Ya-Hui
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Yang, Jinn-Moon
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Chen, Chinpiao
Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells
(2013-04-25)
Yu, Sheng-Yi
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Liu, Huei-Fang
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Wang, Su-Pei
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Chang, Chia-Ching
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Tsai, Chuan-Mei
Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), has been used to treat numerous cancers; however, evidence has shown that cancer cells can become resistant to gefitinib during therapy. Here, we report a human proto-oncogene, securin, which displays resistance to death in cancer cells. Gefitinib treatment decreases securin levels at the protein level by inducing protein instability but did not affect on the securin gene expression. Treatment with gefitinib induced cytotoxicity in various human cancer cell types, including RKO (colon cancer), A549 (lung cancer), BFTC905 (bladder cancer), MCF7 (breast cancer) and A375 (skin cancer). BFTC905 and A549 cells expressed relatively high levels of the phosphorylated and total EGFR proteins; however, A375, MCF7 and RKO cells did not markedly express these proteins. Moreover, following treatment with gefitinib, the securin-wild type cancer cells were more resistant to apoptotic induction than the securin-null cancer cells. Surprisingly, both the securin-wild type and securin-null cancer cells expressed the EGFR protein at similar levels. Treatment with gefitinib induced mitochondrial dysfunction, cytochrome c release, caspase-3 activation and poly (ADP-ribose) polymerase protein cleavage, indicating that apoptosis occurred in these cancer cells. The transfection of a GPF-securin expression vector increased both the proliferation rates and resistance to gefitinib-induced death in these cancer cells. Taken together, these findings demonstrate that the presence of securin promotes resistance to gefitinib-induced apoptosis via an EGFR-independent pathway in human cancer cells. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Optimization of gefitinib analogues with potent anticancer activity
(2014-11-15)
Yin, Kai-Hao
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Hsieh, Yi-Han
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Sulake, Rohidas S.
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Wang, Su-Pei
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Chao, Jui-I.
The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues. (C) 2014 Elsevier Ltd. All rights reserved.
SP-101, a novel gefitinib derivative induces apoptosis and tumor inhibition
(2013-04-01)
Chao, Jui-i
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Wang, Su-Pei
;
Chen, Chinpiao
;
Yang, Jinn-Moon
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生物科技學系