title: 2'-Hydroxycinnamaldehyde induces apoptosis through HSF1-mediated BAG3 expression.
abstract: BAG3, a member of BAG co-chaperone family, is induced by stressful stimuli such as heat shock and heavy metals. Through interaction with various binding partners, BAG3 is thought to play a role in cellular adaptive responses against stressful conditions in normal and neoplastic cells. 2'-Hydroxycinnamaldehyde (HCA) is a natural derivative of cinnamaldehyde and has antitumor activity in various cancer cells. In the present study, for the first time, we identified that HCA induced BAG3 expression and BAG3-mediated apoptosis in cancer cells. The apoptotic cell death induced by HCA was demonstrated by caspase-7, -9 and PARP activation, and confirmed by Annexin V staining in both SW480 and SW620 colon cancer cells. Notably, both the mRNA and protein levels of BAG3 were largely induced by HCA in a dose- and time-dependent manner. By showing transcription factor HSF1 activation, we demonstrated that HCA induces the expression of BAG3 through HSF1 activation. More importantly, knockdown of BAG3 expression using siRNA largely inhibited HCA-induced apoptosis, suggesting that BAG3 is actively involved in HCA-induced cancer cell death. Considering the importance of the stress response mechanism in cancer progression, our results strongly suggest that BAG3 could be a potential target for anticancer therapy.
authors.affiliation: Department of Biochemistry, Dongguk University College of Oriental Medicine, Gyeongju 780-714, Republic of Korea.
authors.forename: Hai-Anh
authors.initials: HA
authors.lastname: Nguyen
authors.affiliation: Department of Biochemistry, Dongguk University College of Oriental Medicine, Gyeongju 780-714, Republic of Korea.
authors.forename: Soo-A
authors.initials: SA
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D000076249:Heat Shock Transcription Factors; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D002934:Cinnamates; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; C117045:p-hydroxycinnamaldehyde