title: Terrein induces apoptosis in HeLa human cervical carcinoma cells through             p53 and ERK regulation.
abstract: Terrein, a fungal metabolite derived from Aspergillus terreus, has been             shown to have a variety of biological activities in human cells including inhibition             of melanogenesis, as well as anti-inflammatory, antioxidant and anticancer properties.             In the present study, terrein was shown to have marked anticancer activity on             HeLa human cervical carcinoma cells. Terrein exhibited inhibition of proliferation             within the same ranges for other cancer cell types with an IC50 at 0.29 mM. The             growth inhibition that induced cell death was via apoptosis mechanisms. Chromatin             condensation was observed using the Hoechst 33342 stain, a DNA-specific dye. The             increase of DNA fragmentation or the sub-G0 peak was also detected by flow cytometry.             The signaling used by terrein to induce apoptosis was via the death-receptor and             mitochondrial pathways; the cleavage of specific fluorogenic substrates by caspase-3,             -8 and -9 activities are clearly demonstrated. The mitochondria were damaged as             demonstrated by the decrease of the red/green ratio of the JC-1 staining and the             increase of the Bax/Bcl-2 expression ratio. Further analysis of the upstream signaling             by the quantitative real-time polymerase chain reaction showed that p53, p21 and             ERK were upregulated which indicates the importance of their roles on terrein             signaling. This study is the first to show that terrein has an effect on the anticancer             properties in cervical cancer cells by inducing apoptosis through p53 and ERK             regulation. Our data may help expand the function of the terrein compound and             may also aid in the discovery of new anticancer agents.
authors: Department of Microbiology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
authors: Yuwarat
authors: Y
authors: Porameesanaporn
authors: Wanlaya
authors: W
authors: Uthaisang-Tanechpongtamb
authors: Faongchat
authors: F
authors: Jarintanan
authors: Suchada
authors: S
authors: Jongrungruangchok
authors: Benjamas
authors: B
authors: Thanomsub Wongsatayanon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001230:Aspergillus / Q000737:chemistry; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003517:Cyclopentanes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C439087:terrein