Toxic profile of marinobufagin from poisonous Amazon toads and antitumoral effects on human colorectal carcinomas

Ferreira, Paulo Michel Pinheiro; Sousa, Lívia Queiroz de; Sousa, Rayran Walter Ramos de; Rodrigues, Domingos de Jesus; Filho, Evaldo dos Santos Monção; Chaves, Mariana Helena; Vieira-Júnior, Gerardo M.; Rizzo, Márcia dos Santos; Filgueiras, Lívia Alves; Mendes, Anderson Nogueira; Lima, Daisy Jereissati Barbosa; Pessoa, Cláudia; Sousa, João Marcelo de Castro e; Rodrigues, Ana Carolina Borges da Cruz; Soares, Milena Botelho Pereira; Bezerra, Daniel Pereira

doi:10.1016/j.jep.2023.116406

Cited by 3 publications

(1 citation statement)

References 76 publications

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“…In this context, natural products have been used as a source of novel anticancer [12][13][14] and antinociceptive [15] agents. Among them, Casearia (Salicaceae) comprises about 180 species distributed in sub-tropical and tropical regions [16] and has promising anticancer effects [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings

Silva,

Beserra Filho,

Acha

et al. 2024

Pharmaceuticals

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Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12–39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.

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Section: Introductionmentioning

confidence: 99%

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings

Silva,

Beserra Filho,

Acha

et al. 2024

Pharmaceuticals

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Hellebrigenin triggers death of promyelocytic leukemia cells by non-genotoxic ways

Cavalcanti,

Soares,

Barreto

et al. 2024

Toxicon

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Ethnozoological importance of Eisenia fetida and experimental validation of its anticancer activity in ascites Dalton’s lymphoma (DL) bearing mice

Borah,

Prasad

2024

Futur J Pharm Sci

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Eisenia fetida, commonly known as the red earthworm, holds significant ethnozoological importance due to its traditional use in various cultures as a medicinal agent. This study aims to explore the potential anticancer effects of Eisenia fetida paste (EFP) and evaluate its therapeutic efficacy in mice with ascites Dalton's lymphoma (DL). The EFP extract demonstrated a significant antitumour effect, possibly by initiating programmed cell death and mitochondrial changes in the tumour cells. The viability of tumour cells exhibited a reduction over time due to EFP treatment. Comparative analysis with the reference drug cisplatin revealed that EFP exhibited fewer or no adverse effects on mutagenicity, hepatotoxicity, and nephrotoxicity in tumour-bearing hosts. EFP treatment was found to show progressive increase in the quantity of apoptotic DL cells over time suggesting a time-dependent impact on the induction of apoptosis in the treated groups. These results imply that EFP might serve as a safer substitute for cancer treatment and hold promise for developing new and improved therapeutic strategies against cancer. The main implication of the study is that EFP might serve as a safer substitute for cancer treatment. It suggests a promising avenue for developing new and improved therapeutic strategies against cancer, with the potential to enhance treatment outcomes while minimising adverse effects. Graphical abstract

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Toxic profile of marinobufagin from poisonous Amazon toads and antitumoral effects on human colorectal carcinomas

Cited by 3 publications

References 76 publications

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings

Hellebrigenin triggers death of promyelocytic leukemia cells by non-genotoxic ways

Ethnozoological importance of Eisenia fetida and experimental validation of its anticancer activity in ascites Dalton’s lymphoma (DL) bearing mice

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