The anticancer effects of actinoporin RTX-A from the sea anemone Heteractis crispa (=Radianthus macrodactylus)

Sergey Fedorov, Sergey Dyshlovoy, Margarita Monastyrnaya, Larisa Shubina, Elena Leychenko, Emma Kozlovskaya, Jun O. Jin, Jong Young Kwak, Ann M. Bode, Zigang Dong, Valentin Stonik

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42 Scopus citations

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)=0.034nM. 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.

Original languageEnglish (US)
Pages (from-to)811-817
Number of pages7
JournalToxicon
Volume55
Issue number4
DOIs
StatePublished - Apr 1 2010

Bibliographical note

Funding 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).

Keywords

  • AP-1
  • Actinoporin
  • Anticancer activity
  • Apoptosis
  • Inhibition of malignant transformation
  • NF-κB
  • P53 nuclear factors

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