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dc.contributor.authorFan, Xing-Xing*
dc.contributor.authorYao, Xiao-Jun*
dc.contributor.authorXu, Su-Wei*
dc.contributor.authorWong, Vincent K-W.*
dc.contributor.authorHe, Jian-Xing*
dc.contributor.authorDing, Jian*
dc.contributor.authorXue, Wei-Wei*
dc.contributor.authorMujtaba, Tahira*
dc.contributor.authorMichelangeli, Francesco*
dc.contributor.authorHuang, Min*
dc.contributor.authorHuang, Jun*
dc.contributor.authorXiao, Da-Kai*
dc.contributor.authorJiang, Ze-Bo*
dc.contributor.authorZhou, Yan-Ling*
dc.contributor.authorKam, Richard K-T.*
dc.contributor.authorLiu, Liang*
dc.contributor.authorLeung, Elaine L-H.*
dc.date.accessioned2016-04-18T09:38:32Z
dc.date.available2016-04-18T09:38:32Z
dc.date.issued06/11/2015
dc.identifier.citationFan, X-X., et. al. (2015). (Z)3,4,5,4'-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level. Scientific Reports, 5, 16348. DOI: 10.1038/srep16348.
dc.identifier.doi10.1038/srep16348
dc.identifier.urihttp://hdl.handle.net/10034/605649
dc.description.abstractCalcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4′-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients.
dc.language.isoenen
dc.publisherNature Publishing Group
dc.relation.urlhttp://www.nature.com/articles/srep16348en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPharmacologyen
dc.subjectMolecular medicineen
dc.title(Z)3,4,5,4'-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level.en
dc.typeArticle
dc.identifier.eissn2045-2322
dc.contributor.departmentUniversity of Birmingham; Macau University; Chongqing University; University of Chester; Chinese Academy of Sciences; Shangai, University of Hong Kong
dc.identifier.journalScientific reportsen
dc.date.accepted2015-10-13
or.grant.openaccessYesen
rioxxterms.funderxxen
rioxxterms.identifier.projectxxen
rioxxterms.versionVoRen
rioxxterms.licenseref.startdate2215-11-06en
refterms.dateFCD2019-07-17T08:47:19Z
refterms.versionFCDVoR
refterms.dateFOA2018-08-13T21:39:00Z
html.description.abstractCalcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4′-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients.


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