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)=0.034nM. Actinoporin RTX-A also was shown to inhibit the phenotype expression of HeLa human cancer cells with an INCC 50=0.03nM. 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 4.66nM), 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-κB, 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-κB nuclear factors activity.
Bibliographical noteFunding Information:
This work was supported in part by The Hormel Foundation and National Institutes of Health grants CA81064, CA77646 and CA88961; by the Grant 2813.2008.4 for Support of the Leading Russian Science Schools, Program of Presidium of RAS “Molecular and Cell Biology” 09-I-Π22-05 and 09-I-Π22-06, Grant RFBR 08-04-01052-a and FEB RAS Grants 09-III-B-05-155, 09-III-A-05-146, 09-III-A-05-141. The Korean co-authors are grateful for financial support from the National Research Foundation of Korea (NRF) (No. R13-2002-044-04001-0).
- Anticancer activity
- Inhibition of malignant transformation
- P53 nuclear factors