The anticancer effects of actinoporin RTX-A from the sea anemone Heteractis crispa (=Radianthus macrodactylus).
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.
Fedorov
Sergey
S
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
Dyshlovoy
Sergey
S
Monastyrnaya
Margarita
M
Shubina
Larisa
L
Leychenko
Elena
E
Kozlovskaya
Emma
E
Jin
Jun-O
JO
Kwak
Jong-Young
JY
Bode
Ann M
AM
Dong
Zigang
Z
Stonik
Valentin
V
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
D000970:Antineoplastic Agents; D003064:Cnidarian Venoms; C549943:actinoporin RTX-A, Heteractis crispa; D004815:Epidermal Growth Factor