title: The anticancer effects of actinoporin RTX-A from the sea anemone Heteractis crispa (=Radianthus macrodactylus).
abstract: Four isoforms of actinoporins were isolated in 2002-2004 from the tropical sea anemone Heteractis crispa (=Radianthus macrodactylus). Their potent hemolytic activities and effects on Ehrlich ascites carcinoma bearing mice were also studied. In this study, the individual actinoporin (RTX-A) demonstrated potential cancer-preventive activity at extremely low and non-cytotoxic concentrations. The substance suppressed the malignant transformation of mouse JB6 P(+) Cl41 cells stimulated by epidermal growth factor (EGF) in soft agar with the inhibition of number of the colonies C(50) (INCC(50))=0.034 nM. Actinoporin RTX-A also was shown to inhibit the phenotype expression of HeLa human cancer cells with an INCC(50)=0.03 nM. The cytotoxic effect of RTX-A against JB6 P(+) Cl41 cells and HeLa, THP-1, MDA-MB-231, and SNU-C4 human tumor cell lines was high (IC(50)=0.57, 2.26, 1.11, 30.0 and 4.66 nM), but significantly less than their capacity to suppress tumor cell colony formation or phenotype expression. RTX-A also induced apoptosis and inhibited basal AP-1, NF-kappaB, and p53-dependent transcriptional activity in JB6 Cl41 cells. These results confirmed that actinoporin RTX-A from H. crispa, at least partially, might exhibit cancer-preventive and anticancer cytotoxic properties through the induction of p53-independent apoptosis and inhibition of the oncogenic AP-1 and NF-kappaB nuclear factors activity.
authors: Pacific Institute of Bioorganic Chemistry of the Far Eastern Branch of the Russian Academy of Sciences, pr. 100 let Vladivostoku, 159, Vladivostok 690022, Russia. fedorov@piboc.dvo.ru
authors: Sergey
authors: S
authors: Fedorov
authors: Sergey
authors: S
authors: Dyshlovoy
authors: Margarita
authors: M
authors: Monastyrnaya
authors: Larisa
authors: L
authors: Shubina
authors: Elena
authors: E
authors: Leychenko
authors: Emma
authors: E
authors: Kozlovskaya
authors: Jun-O
authors: JO
authors: Jin
authors: Jong-Young
authors: JY
authors: Kwak
authors: Ann M
authors: AM
authors: Bode
authors: Zigang
authors: Z
authors: Dong
authors: Valentin
authors: V
authors: Stonik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051379:Mice; D012615:Sea Anemones / Q000737:chemistry*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003064:Cnidarian Venoms; C549943:actinoporin RTX-A, Heteractis crispa; D004815:Epidermal Growth Factor