Cytotoxic profile of natural and some modified bufadienolides from toad Rhinella schneideri parotoid gland secretion

Cunha-Filho, Geraldino; Resck, Inês S.; Cavalcanti, Bruno C.; Pessoa, Cláudia; Moraes, Manoel Odoríco de; Ferreira, José R.O.; Rodrigues, Felipe Augusto Rocha; Santos, Maria Lucília dos

doi:10.1016/j.toxicon.2010.03.021

Cited by 79 publications

(45 citation statements)

References 74 publications

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“…A recent paper of Cunha-Filho and colleagues on compounds not listed in the present review (among them telocinobufagin) confirms this observation [99].…”

supporting

confidence: 81%

Cardiotonic Steroids-Mediated Targeting of the Na+/K+-ATPase to Combat Chemoresistant Cancers

Mijatovic¹,

Dufrasne²,

Kiss

2012

CMC

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A large proportion of cancer patients fail to respond to conventional chemotherapy because of the intrinsic resistance of their cancer to pro-apoptotic stimuli and/or the acquisition of a multidrug resistant (MDR) phenotype during chronic chemotherapy. A new angle in chemotherapeutics against these cancer types associated with dismal prognoses would be the targeting of specific ion channels and pumps over expressed by cancer cells as compared to normal cells. Several reports suggest that the alpha subunits of the Na(+)/K(+)-ATPase (referred as sodium pump from now on) could be such targets, using cardiotonic steroids (CS) including cardenolides and bufadienolides. A significant proportion of non-small-cell-lung cancers (NSCLCs), glioblastomas (GBMs), melanomas and kidney cancers overexpresses the alpha-1 subunit of the sodium pump as compared to corresponding normal tissues, while colon cancers overexpress the alpha-3 subunit. Thus, a deeper knowledge of the structure-activity relationship (SAR), in terms of CS-mediated anticancer effects, to the sodium pump alpha subunits might enable the identification of potent anticancer agents with limited cardiotoxicity. The current review provides an in depth SAR analysis with respect to cardenolide- versus bufadienolide-mediated anticancer effects. Moreover, pharmacological data from in vitro and in vivo experiments, as well as pre-clinical and clinical trials regarding cardenolides to combat cancers associated with dismal prognoses are presented.

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“…A recent paper of Cunha-Filho and colleagues on compounds not listed in the present review (among them telocinobufagin) confirms this observation [99].…”

supporting

confidence: 81%

Cardiotonic Steroids-Mediated Targeting of the Na+/K+-ATPase to Combat Chemoresistant Cancers

Mijatovic¹,

Dufrasne²,

Kiss

2012

CMC

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“…The bufadienolides telocinobufagin and marinobufagin were isolated from the Brazilian toad Rhinella schneideri parotoid glands secretion by chromatographic separation on neutral aluminum oxide column and chemically characterized by spectrometric data, as previously described (Cunha-Filho et al, 2010). Digoxin and ouabain were obtained from Sigma-Aldrich (USA).…”

Section: Drugsmentioning

confidence: 99%

Inhibitory effect of combinations of digoxin and endogenous cardiotonic steroids on Na+/K+-ATPase activity in human kidney membrane preparation

et al. 2011

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Considering the extensive use of digoxin in the treatment of heart failure and the recent findings that endogenous cardiac glycosides may have altered levels in many diseases, including heart failure, the demonstration of additive effect between cardiac glycosides can help in the understanding of recent clinical observations, including that lower than usual doses of cardiac glycosides are necessary for decreasing mortality in these patients.

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“…This species is found in South America and is characterized by the presence of parotoid glands in the postorbital region (Jared et al, 2009). Few studies have described the isolation and biological and toxic effects of molecules from the parotoid secretion of R. schneideri (Cunha-Filho et al, 2010;Anjolette et al, 2011). In the literature, only one study has described the peptide profile of this secretion .…”

mentioning

confidence: 99%

Biochemical Profile, Biological Activities, and Toxic Effects of Proteins in the Rhinella schneideri Parotoid Gland Secretion

Sousa-Filho¹,

Freitas²,

Lobo

et al. 2016

J. Exp. Zool.

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Parotoid glands of amphibians are known for the production of several biologically active compounds having pharmacological and toxic effects in mammals. In the present work, a protein fraction obtained from Rhinella schneideri parotoid gland (RsPP) was characterized to study its biological and toxic effects. Rhinella schneideri parotoid secretion is composed of up to 30% (w/w) of soluble proteins. Tandem mass spectrometric analysis of the RsPP identified 104 proteins, including actin, beta-actin, ribosomal proteins, catalase, galectin, and uncharacterized proteins; however, no peptidases were found, and this result was reinforced by the absence of proteolytic activity. In addition, RsPP did not exhibit pro-coagulant or antibacterial effects. However, pretreatment of mice with different doses of RsPP intraperitoneally inhibited carrageenan-induced paw edema and increased tissue myeloperoxidase activity. RsPP also reduced interleukin 1β levels in the peritoneal cavities and cell migration in the peritoneal cavities of an animal model of carrageenan-induced peritonitis. Subchronic treatment of animals with RsPP for 7 consecutive days did not alter the serum biochemical, renal, or liver parameters. However, a significant reduction in blood leukocyte count was observed. Our results showed that R. schneideri parotoid secretion contains proteins with anti-inflammatory and slight toxic effects.

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Cytotoxic profile of natural and some modified bufadienolides from toad Rhinella schneideri parotoid gland secretion

Cited by 79 publications

References 74 publications

Cardiotonic Steroids-Mediated Targeting of the Na+/K+-ATPase to Combat Chemoresistant Cancers

Cardiotonic Steroids-Mediated Targeting of the Na+/K+-ATPase to Combat Chemoresistant Cancers

Inhibitory effect of combinations of digoxin and endogenous cardiotonic steroids on Na+/K+-ATPase activity in human kidney membrane preparation

Biochemical Profile, Biological Activities, and Toxic Effects of Proteins in the Rhinella schneideri Parotoid Gland Secretion

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