(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.

Hdl Handle:
http://hdl.handle.net/10034/605649
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.
Authors:
Fan, Xing-Xing; Yao, Xiao-Jun; Xu, Su Wei; Wong, Vincent K-W.; He, Jian-Xing; Ding, Jian; Xue, Wei-Wei; Mujtaba, Tahira; Michelangeli, Francesco; Huang, Min; Huang, Jun; Xiao, Da-Kai; Jiang, Ze-Bo; Zhou, Yan-Ling; Kam, Richard K-T.; Liu, Liang; Leung, Elaine L-H.
Abstract:
Calcium 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.
Affiliation:
University of Birmingham; Macau University; Chongqing University; University of Chester; Chinese Academy of Sciences; Shangai, University of Hong Kong
Citation:
Fan, 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.
Publisher:
Nature Publishing Group
Journal:
Scientific reports
Publication Date:
6-Nov-2015
URI:
http://hdl.handle.net/10034/605649
DOI:
10.1038/srep16348
Additional Links:
http://www.nature.com/articles/srep16348
Type:
Article
Language:
en
EISSN:
2045-2322
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorFan, Xing-Xingen
dc.contributor.authorYao, Xiao-Junen
dc.contributor.authorXu, Su Weien
dc.contributor.authorWong, Vincent K-W.en
dc.contributor.authorHe, Jian-Xingen
dc.contributor.authorDing, Jianen
dc.contributor.authorXue, Wei-Weien
dc.contributor.authorMujtaba, Tahiraen
dc.contributor.authorMichelangeli, Francescoen
dc.contributor.authorHuang, Minen
dc.contributor.authorHuang, Junen
dc.contributor.authorXiao, Da-Kaien
dc.contributor.authorJiang, Ze-Boen
dc.contributor.authorZhou, Yan-Lingen
dc.contributor.authorKam, Richard K-T.en
dc.contributor.authorLiu, Liangen
dc.contributor.authorLeung, Elaine L-H.en
dc.date.accessioned2016-04-18T09:38:32Zen
dc.date.available2016-04-18T09:38:32Zen
dc.date.issued2015-11-06en
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.en
dc.identifier.doi10.1038/srep16348en
dc.identifier.urihttp://hdl.handle.net/10034/605649en
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.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
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.typeArticleen
dc.identifier.eissn2045-2322en
dc.contributor.departmentUniversity of Birmingham; Macau University; Chongqing University; University of Chester; Chinese Academy of Sciences; Shangai, University of Hong Kongen
dc.identifier.journalScientific reportsen
dc.date.accepted2015-10-13en
or.grant.openaccessYesen
rioxxterms.funderxxen
rioxxterms.identifier.projectxxen
rioxxterms.versionVoRen
rioxxterms.licenseref.startdate2215-11-06en
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