DOI: 10.1073/pnas.95.7.3380. Anticancer action of cubé insecticide: Correlation for rotenoid constituents between inhibition of NADH:ubiquinone oxidoreductase and induced ornithine decarboxylase activities

Anticancer action of cubé insecticide: Correlation for rotenoid constituents between inhibition of NADH:ubiquinone oxidoreductase and induced ornithine decarboxylase activities

10.1073/pnas.95.7.3380

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Rotenone and rotenoid-containing botanicals, important insecticides and fish poisons, are reported to have anticancer activity in rats and mice. The toxic action of rotenone is attributed to inhibition of NADH:ubiquinone oxidoreductase activity and the purported cancer chemopreventive effect of deguelin analogs has been associated with inhibition of phorbol ester-induced ornithine decarboxylase (ODC) activity. This study defines a possible relationship between these two types of activity important in evaluating the toxicology of rotenoid pesticides and the suitability of the anticancer model. Fractionation of cubé resin (the commercial rotenoid pesticide) establishes that the activity in both assays is due primarily to rotenone (IC 50 = 0.8–4 nM), secondarily to deguelin, and in small part to rotenolone and tephrosin. In addition, the potency of 29 rotenoids from cubé insecticide for inhibiting NADH:ubiquinone oxidoreductase in vitro assayed with bovine heart electron transport particles satisfactorily predicts their potency in vivo in the induced ODC assay using noncytotoxic rotenoid concentrations with cultured MCF-7 human breast cancer cells ( r = 0.86). Clearly the molecular features of rotenoids essential for inhibiting NADH:ubiquinone oxidoreductase are similar to those for blocking ODC induction. This apparent correlation extends to 11 flavonoids and stilbenoids from cubé resin ( r = 0.98) and genistein and resveratrol except for lower potency and less selectivity than the rotenoids relative to cytotoxicity. These findings on cubé insecticide constituents and our earlier study comparing rotenone and pyridaben miticide indicate that inhibition of NADH:ubiquinone oxidoreductase activity lowers the level of induced ODC activity leading to the antiproliferative effect and anticancer action.

Bibliography

Fang, N., & Casida, J. E. (1998). Anticancer action of cubÃ© insecticide: Correlation for rotenoid constituents between inhibition of NADH:ubiquinone oxidoreductase and induced ornithine decarboxylase activities. Proceedings of the National Academy of Sciences, 95(7), 3380â3384.

Authors 2

Nianbai Fang (first)
John E. Casida (additional)

References 29 Referenced 144

W O Negherbohn Handbook of Toxicology (Saunders, Philadelphia) III, 661–673 (1959). / Handbook of Toxicology by Negherbohn W O (1959)
H Fukami, M Nakajima Naturally Occurring Insecticides, eds M Jacobson, D G Crosby (Dekker, New York), pp. 71–97 (1971). / Naturally Occurring Insecticides by Fukami H (1971)
Lake Davis Northern Pike Eradication Project, January 1997, Final Environmental Impact Report (The Resources Agency, Sacramento, CA, 1997). / Lake Davis Northern Pike Eradication Project, January 1997, Final Environmental Impact Report (1997)
10.1007/978-1-4899-2212-0_10
R M Hollingworth, K I Ahammadsahib Rev Pestic Toxicol 3, 277–302 (1995). / Rev Pestic Toxicol by Hollingworth R M (1995)
10.1016/0304-3835(95)03869-X
10.1016/0041-008X(65)90038-4
10.1038/nm0395-260
10.1016/S0031-9422(00)89755-1
10.1016/0014-2964(73)90140-0
M Gosálvez, R García-Cañero, M Blanco, C Gurucharri-Lloyd Cancer Treat Rep 60, 1–8 (1976). / Cancer Treat Rep by Gosálvez M (1976)
Gerhäuser C. Kosmeder J. W. II Lee S. K. Mar W. Moriarity R. M. & Pezzuto J. M. (1996) Am. Chem. Soc. Abstr. 211 (1–2) MEDI 81.
J C Rowlands, J E Casida The Toxicologist 36, 235 (1997). / The Toxicologist by Rowlands J C (1997)
E P Killip, A C Smith J Washington Acad Sci 20, 74–81 (1930). / J Washington Acad Sci by Killip E P (1930)
10.1021/jo961604h
10.1021/tx9700432
G O Udeani, C Gerhäuser, C F Thomas, R C Moon, J W Kosmeder, A D Kinghorn, R M Moriarty, J M Pezzuto Cancer Res 57, 3424–3428 (1997). / Cancer Res by Udeani G O (1997)
10.3181/00379727-208-43843
10.1126/science.275.5297.218
10.1006/pest.1996.0017
10.1016/0006-3002(56)90058-0
10.1002/jcp.1041130312
E Geoffroy Ann Inst Colon Marseille 2, 1–86 (1895). / Ann Inst Colon Marseille by Geoffroy E (1895)
10.1021/np50044a013
10.1016/0031-9422(96)00134-3
10.1039/p19730001285
10.1039/p19920000839
10.1584/jpestics.19.4_S243
G L Law, R-S Li, D R Morris Polyamines: Regulation and Molecular Interaction, ed R A Casero (Landes, Austin, TX), pp. 5–26 (1995). / Polyamines: Regulation and Molecular Interaction by Law G L (1995)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:46 p.m.)
Indexed	1 month ago (July 22, 2025, 6:35 a.m.)
Issued	27 years, 4 months ago (March 31, 1998)
Published	27 years, 4 months ago (March 31, 1998)
Published Online	27 years, 4 months ago (March 31, 1998)
Published Print	27 years, 4 months ago (March 31, 1998)

Funders 0

None

BibTeX

@article{Fang_1998, title={Anticancer action of cubé insecticide: Correlation for rotenoid constituents between inhibition of NADH:ubiquinone oxidoreductase and induced ornithine decarboxylase activities}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.7.3380}, DOI={10.1073/pnas.95.7.3380}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Fang, Nianbai and Casida, John E.}, year={1998}, month=mar, pages={3380–3384} }

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