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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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

Keywords

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

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    Fedorov, S., Dyshlovoy, S., Monastyrnaya, M., Shubina, L., Leychenko, E., Kozlovskaya, E., Jin, J. O., Kwak, J. Y., Bode, A. M., Dong, Z., & Stonik, V. (2010). The anticancer effects of actinoporin RTX-A from the sea anemone Heteractis crispa (=Radianthus macrodactylus). Toxicon, 55(4), 811-817. https://doi.org/10.1016/j.toxicon.2009.11.016