title: Capsaicin induces apoptosis in PC12 cells through ER stress.
abstract: Capsaicin, the pungent agent in chili peppers, has been shown to act as a tumor-suppressor in cancer. In our previous study, capsaicin was shown to induce apoptosis in the rat pheochromocytoma cell line (PC12 cells). Thus, the aim of the present study was to determine the potential mechanism by which capsaicin induces apoptosis. We treated PC12 cells with 50, 100 and 500 µM capsaicin and measured the reticular calcium content and expression of the reticular calcium transport systems. These results were correlated with endoplasmic reticulum (ER) stress markers CHOP, ATF4 and X-box binding protein 1 (XBP1), as well as with apoptosis induction. We observed that capsaicin decreased reticular calcium in a concentration-dependent manner. Simultaneously, expression levels of the sarco/endoplasmic reticulum pump and ryanodin receptor of type 2 were modified. These changes were accompanied by increased ER stress, as documented by increased stress markers. Thus, from these results we propose that in PC12 cells capsaicin induces apoptosis through increased ER stress.
authors: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, 833 34 Bratislava, Slovak Republic.
authors: Olga
authors: O
authors: Krizanova
authors: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, 833 34 Bratislava, Slovak Republic.
authors: Iveta
authors: I
authors: Steliarova
authors: Molecular Medicine Center, Slovak Academy of Sciences, 831 01 Bratislava, Slovak Republic.
authors: Lucia
authors: L
authors: Csaderova
authors: Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic.
authors: Michal
authors: M
authors: Pastorek
authors: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, 833 34 Bratislava, Slovak Republic.
authors: Sona
authors: S
authors: Hudecova
mesh_terms: D051701:Activating Transcription Factor 4 / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000982:Antipruritics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D000071701:Regulatory Factor X Transcription Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000071717:X-Box Binding Protein 1
chemical_list: D000982:Antipruritics; C497110:Atf4 protein, rat; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D019837:Ryanodine Receptor Calcium Release Channel; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D002211:Capsaicin; D002118:Calcium