Selective cytotoxicity of squamocin on T24 bladder cancer cells at the S-phase via a Bax-, Bad-, and caspase-3-related pathways.
Annonaceous acetogenins are a group of potential anti-neoplastic agents isolated from Annonaceae plants. We purified squamocin, a cytotoxic bis-tetrahydrofuran acetogenin, from the seeds of Annona reticulata and analyzed its biologic effects on cancer cells. We showed that squamocin was cytotoxic to all the cancer lines tested. Furthermore, squamocin arrested T24 bladder cancer cells at the G1 phase and caused a selective cytotoxicity on S-phase-enriched T24 cells. It induced the expression of Bax and Bad pro-apoptotic genes, enhanced caspase-3 activity, cleaved the functional protein of PARP and caused cell apoptosis. These results suggest that squamocin is a potentially promising anticancer compound.
Yuan
Shyng-Shiou F
SS
Department of Medical Research, E-DA Hospital, I-Shou University, Kaoshiung County, Taiwan 824, ROC. yuanssf@ms33.hinet.net
Chang
Hsueh-Ling
HL
Chen
Hsiao-Wen
HW
Kuo
Fu-Chen
FC
Liaw
Chih-Chuang
CC
Su
Jinu-Huang
JH
Wu
Yang-Chang
YC
D029061:Annonaceae / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D005663:Furans / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000633:toxicity*; D010936:Plant Extracts / Q000633:toxicity; D016196:S Phase / Q000187:drug effects*; D012639:Seeds / Q000737:chemistry; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C494826:BAX protein, human; D005663:Furans; D007783:Lactones; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C059660:squamocin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases