title: Role of altholactone in inducing type II apoptosis signalling pathway and expression of cancer-related genes in cervical carcinoma HeLa cell line.
abstract: Goniothalamus species (Annonaceae) is a shrub that grows in the rainforest of tropical Asia. Several compounds have been isolated and exhibit the potential use for cancer treatment. In this work, altholactone isolated from Goniothalamus macrophyllus was investigated for its cytotoxicity, apoptosis signalling and the expression of cancer-related genes in the cervical carcinoma HeLa cells. Cytotoxicity was evaluated by MTT assay. Apoptotic characteristics were evaluated by morphological studies. Caspase-3 activity was detected using a fluorogenic substrate. Cytochrome c release from mitochondria and protein Bid were determined by Western blotting and cancer-related genes expression by RT-PCR. The results demonstrated that altholactone was cytotoxic to HeLa (IC50  = 9.6 μg/mL), and apoptotic cell death was manifested by appearance of chromatin condensation and caspase-3 activation, which was inhibited by specific inhibitors of both caspase-8 and -9. Release into the cytosol of cytochrome and cleavage of Bid occurred. Altholactone also caused a decrease in bcl-2 and an increase in p53 expression. These unique properties of altholactone suggest a potential for cancer chemotherapy.
authors.affiliation: Faculty of Medicine, Department of Biochemistry, Srinakharinwirot University, Bangkok 10110, Thailand. wanlaya@swu.ac.th
authors.forename: Wanlaya
authors.initials: W
authors.lastname: Uthaisang-Tanechpongtamb
authors.forename: Promjit
authors.initials: P
authors.lastname: Sriyabhaya
authors.forename: Prapon
authors.initials: P
authors.lastname: Wilairat
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000737:chemistry / Q000378:metabolism; D053453:Caspase 9 / Q000737:chemistry / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D054335:Goniothalamus / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D005663:Furans; D019253:Proto-Oncogene Proteins c-bcl-2; D011753:Pyrones; D016159:Tumor Suppressor Protein p53; C459359:altholactone; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9