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

doi:10.1016/j.toxicon.2009.11.016

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

The Hormel Institute

Research output: Contribution to journal › Article › peer-review

67 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 language	English (US)
Pages (from-to)	811-817
Number of pages	7
Journal	Toxicon
Volume	55
Issue number	4
DOIs	https://doi.org/10.1016/j.toxicon.2009.11.016
State	Published - 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).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Publisher link

10.1016/j.toxicon.2009.11.016

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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)=0.034nM. 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.",

keywords = "AP-1, Actinoporin, Anticancer activity, Apoptosis, Inhibition of malignant transformation, NF-κB, P53 nuclear factors",

author = "Sergey Fedorov and Sergey Dyshlovoy and Margarita Monastyrnaya and Larisa Shubina and Elena Leychenko and Emma Kozlovskaya and Jin, \{Jun O.\} and Kwak, \{Jong Young\} and Bode, \{Ann M.\} and Zigang Dong and Valentin Stonik",

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 {\textquotedblleft}Molecular and Cell Biology{\textquotedblright} 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). ",

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doi = "10.1016/j.toxicon.2009.11.016",

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T1 - The anticancer effects of actinoporin RTX-A from the sea anemone Heteractis crispa (=Radianthus macrodactylus)

AU - Fedorov, Sergey

AU - Dyshlovoy, Sergey

AU - Monastyrnaya, Margarita

AU - Shubina, Larisa

AU - Leychenko, Elena

AU - Kozlovskaya, Emma

AU - Jin, Jun O.

AU - Kwak, Jong Young

AU - Bode, Ann M.

AU - Dong, Zigang

AU - Stonik, Valentin

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Y1 - 2010/4/1

N2 - 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.

AB - 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.

KW - AP-1

KW - Actinoporin

KW - Anticancer activity

KW - Apoptosis

KW - Inhibition of malignant transformation

KW - NF-κB

KW - P53 nuclear factors

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

Abstract

Bibliographical note

UN SDGs

Keywords

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