Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells

Machado, Kátia da Conceição; Sousa, Lívia Queiroz de; Lima, Daisy Jereissati Barbosa; Soares, Bruno Moreira; Cavalcanti, Bruno C.; Maranhão, Sarah Sant’Anna; Noronha, Janaina da Costa de; Rodrigues, Domingos de Jesus; Militão, Gardênia Carmen Gadelha; Chaves, Mariana Helena; Vieira-Júnior, Gerardo M.; Pessoa, Cláudia; Moraes, Manoel Odoríco de; Sousa, João Marcelo de Castro e; Melo‐Cavalcante, Ana Amélia de Carvalho; Ferreira, Paulo Michel Pinheiro

doi:10.1016/j.toxlet.2017.12.018

Cited by 21 publications

(15 citation statements)

References 70 publications

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“…Bufalin was also observed to induce apoptosis (Watabe et al 1998;Han et al 2007), mitochondrial dysfunction and increase radiosensitivity in glioblastoma cells (Zhang et al 2017) and to reverse acquired resistance to antineoplastic agents (Sun et al 2017). Marinobufagin showed cytotoxic activity in tests with four tumor cell lines (HL-60, HCT-116, OVCAR-8 and SF-295), as well as toxicity, cytotoxicity and genotoxicity in the root meristem of Allium cepa, through changes in root growth, inhibition of mitotic index, and chromosomal aberrations (Machado et al 2018).…”

Section: Resultsmentioning

confidence: 98%

Evaluation of antimutagenic and cytotoxic activity of skin secretion extract of Rhinella marina and Rhaebo guttatus (Anura, Bufonidae)

et al. 2019

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The skin secretion from toads of the Bufonidae family has great potential in the search for new active compounds to be used as drug candidates in treating some diseases, among them cancer. In this context, this study aimed to evaluate the cytotoxic and antimutagenic activity of the parotoid gland secretion extracts of Rhinella marina and Rhaebo guttatus, as well as biochemically analyze transaminases and serum creatinine for liver and renal damage, respectively. Cytotoxicity was performed by the colorimetric method based on MTT (3- [4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide) with different concentrations of the extracts in Walker or splenic tumor cell cultures from rats and mice. The micronucleus test was performed with male Swiss mice treated orally with the extracts for 15 days, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg kg-1). Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. The extracts showed cytotoxic activity in the evaluated cells. There was a significant reduction in the frequency of MNPCE (R. marina = 56% and R. guttatus = 75%, p < 0.001), indicating antimutagenic potential of the extracts. The groups treated only with extract showed an increase in MNPCE frequency, evidencing mutagenic potential. Biochemical analyzes showed no significant difference between treatments. Thus, under our experimental conditions, the extracts of R. marina and R. guttatus skin secretions presented chemopreventive potential for cancer.

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Section: Resultsmentioning

confidence: 98%

Evaluation of antimutagenic and cytotoxic activity of skin secretion extract of Rhinella marina and Rhaebo guttatus (Anura, Bufonidae)

et al. 2019

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“…These compounds are responsible for a large panel of potential therapeutic indications such as cardiotonic/anti-arrhythmic, antidiabetic, immunomodulatory, antibacterial/antifungal, antiprotozoal, antiviral, antineoplastic, sleep inducing, analgesic, contraceptive, endocrine activity, behavioral changes or wound healing [19,20]. Among antiproliferative activities, some specific ones have already been highlighted on melanoma cells [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the Compounds of Two Different Venoms

Soumoy

Wells

Najem

et al. 2020

Biology

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Melanoma is the most common cancer in young adults, with a constantly increasing incidence. Metastatic melanoma is a very aggressive cancer with a 5-year survival rate of about 22−25%. This is, in most cases, due to a lack of therapies which are effective on the long term. Hence, it is crucial to find new therapeutic agents to increase patient survival. Toad venoms are a rich source of potentially pharmaceutically active compounds and studies have highlighted their possible effect on cancer cells. We focused on the venoms of two different toad species: Bufo bufo and Rhinella marina. We screened the venom crude extracts, the fractions from crude extracts and isolated biomolecules by studying their antiproliferative properties on melanoma cells aiming to determine the compound or the combination of compounds with the highest antiproliferative effect. Our results indicated strong antiproliferative capacities of toad venoms on melanoma cells. We found that these effects were mainly due to bufadienolides that are cardiotonic steroids potentially acting on the Na+/K+ ATPase pump which is overexpressed in melanoma. Finally, our results indicated that bufalin alone was the most interesting compound among the isolated bufadienolides because it had the highest antiproliferative activity on melanoma cells.

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“…When levels of MBG are increased, levels of Fli1 decrease and a Col-1 gene promoter is released from the nucleus and procollagen-1 and collagen become activated [32]. While many studies have demonstrated that Fli1 is a pro-cancer factor [68,69], CS including MBG are becoming attractive anti-cancer drug candidates [70,71]. It is generally accepted that PE is associated with a low risk of cancer, which is not surprising considering that endogenous levels of MBG and other CS are dramatically increased in PE patients [27,28] and therefore suppress the growth of tumors in vivo and in vitro [72][73][74].…”

Section: Interaction Of Cs and Fli1 And A Hint For Cancermentioning

confidence: 99%

Preeclampsia: Cardiotonic Steroids, Fibrosis, Fli1 and Hint to Carcinogenesis

Agalakova

Kolodkin

Adair

et al. 2021

IJMS

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Despite prophylaxis and attempts to select a therapy, the frequency of preeclampsia does not decrease and it still takes the leading position in the structure of maternal mortality and morbidity worldwide. In this review, we present a new theory of the etiology and pathogenesis of preeclampsia that is based on the interaction of Na/K-ATPase and its endogenous ligands including marinobufagenin. The signaling pathway of marinobufagenin involves an inhibition of transcriptional factor Fli1, a negative regulator of collagen synthesis, followed by the deposition of collagen in the vascular tissues and altered vascular functions. Moreover, in vitro and in vivo neutralization of marinobufagenin is associated with the restoration of Fli1. The inverse relationship between marinobufagenin and Fli1 opens new possibilities in the treatment of cancer; as Fli1 is a proto-oncogene, a hypothesis on the suppression of Fli1 by cardiotonic steroids as a potential anti-tumor therapeutic strategy is discussed as well. We propose a novel therapy of preeclampsia that is based on immunoneutralization of the marinobufagenin by monoclonal antibodies, which is capable of impairing marinobufagenin-Na/K-ATPase interactions.

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Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells

Cited by 21 publications

References 70 publications

Evaluation of antimutagenic and cytotoxic activity of skin secretion extract of Rhinella marina and Rhaebo guttatus (Anura, Bufonidae)

Evaluation of antimutagenic and cytotoxic activity of skin secretion extract of Rhinella marina and Rhaebo guttatus (Anura, Bufonidae)

Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the Compounds of Two Different Venoms

Preeclampsia: Cardiotonic Steroids, Fibrosis, Fli1 and Hint to Carcinogenesis

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