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Honeybee venom synergistically enhances the cytotoxic effect of CNS drugs IN HT-29 colon and MCF-7 breast cancer cell lines

2022Journal article Open access
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dc.contributor.authorDuarte, Diana
dc.contributor.authorFalcão, Soraia
dc.contributor.authorEl Mehdi, Iouraouine
dc.contributor.authorVilas-Boas, Miguel
dc.contributor.authorVale, Nuno
dc.date.accessioned2022-03-14T09:58:32Z
dc.date.available2022-03-14T09:58:32Z
dc.date.issued2022
dc.description.abstract5-fluorouracil (5-FU) and doxorubicin (DOX) are potent anti-tumour agents commonly used for colon and breast cancer therapy, respectively. However, their clinical application is limited by their side effects and the development of drug resistance. Honeybee venom is a complex mixture of substances that has been reported to be effective against different cancer cells. Its active compound is melittin, a positively charged amphipathic peptide that interacts with the phospholipids of the cell membrane, forming pores that enable the internalization of small molecules with cytotoxic activities,. and consequently, causing cell death. Some central nervous system (CNS) drugs have recently demonstrated great anti-cancer potential, both in vitro, in vivo and in clinical trials, being promising candidates for drug repurposing in oncology. The present work evaluated the anti-cancer efficacy of honeybee venom in combination with chemotherapeutic or CNS drugs in HT-29 colon and MCF-7 breast cancer cell lines. The chemical characterization of a Portuguese sample of honeybee venom was done by LC-DAD-ESI/MSn analysis. For single treatments, cells were incubated with increasing concentrations of bee venom. For combination treatments, increasing concentrations of bee venom were first combined with the half-maximal inhibitory concentration (IC50) of 5-FU and DOX, in HT-29 and MCF-7 cells, respectively. Cells were also treated with increasing concentrations of bee venom in combination with the IC50 value of four CNS drugs (fluphenazine, fluoxetine, sertraline and thioridazine). Cytotoxicity was evaluated by MTT and SRB assays. The combination index (CI) value was calculated using CompuSyn software, based on the Chou–Talalay method. Synergy scores of different reference models (HSA, Loewe, ZIP and Bliss) were also calculated using SynergyFinder. The results demonstrate that honeybee venom is active against HT-29 colon and MCF-7 breast cancer cells, having better anti-tumour activity in MCF-7 cells. It was found that bee venom combined with 5-FU and fluphenazine in HT-29 cells resulted in less cytotoxic effects compared to the co-treatment of fluoxetine, sertraline and thioridazine plus bee venom, which resulted in less than 15% of viable cells for the whole range of concentrations. The combination of MCF-7 cells with repurposed drugs plus honeybee venom resulted in better anti-cancer efficacies than with DOX, notably for lower concentrations. A combination of fluoxetine and thioridazine plus honeybee venom resulted in less than 40% of viable cells for all ranges of concentrations. These results support that the combination of honeybee venom with repurposed drugs and chemotherapeutic agents can help improve their anti-cancer activity, especially for lower concentrations, in both cell lines. Overall, the present study corroborates the enormous bioactive potential of honeybee venom for colon and breast cancer treatments, both alone and in combination with chemotherapy or repurposed drugs.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationDuarte, Diana; Falcão, Soraia; El Mehdi, Iouraouine; Vilas-Boas, Miguel; Vale, Nuno (2022). Honeybee venom synergistically enhances the cytotoxic effect of CNS drugs IN HT-29 colon and MCF-7 breast cancer cell lines. Pharmaceutics ISSN 1999-4923. 14:3, p. 1-14pt_PT
dc.identifier.doi10.3390/pharmaceutics14030511pt_PT
dc.identifier.issn1999-4923
dc.identifier.urihttp://hdl.handle.net/10198/25209
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHoneybee Venompt_PT
dc.subjectMelittinpt_PT
dc.subjectColorectal cancerpt_PT
dc.subjectBreast cancerpt_PT
dc.subjectDrug combinationpt_PT
dc.subjectAntineoplastic drugspt_PT
dc.subjectCNS drugspt_PT
dc.subjectDrug repurposingpt_PT
dc.titleHoneybee venom synergistically enhances the cytotoxic effect of CNS drugs IN HT-29 colon and MCF-7 breast cancer cell linespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue3pt_PT
oaire.citation.startPage511pt_PT
oaire.citation.titlePharmaceuticspt_PT
oaire.citation.volume14pt_PT
person.familyNameFalcão
person.familyNameVilas-Boas
person.givenNameSoraia
person.givenNameMiguel
person.identifier711432
person.identifier1693134
person.identifier.ciencia-idD41A-6BED-4CBB
person.identifier.ciencia-idA918-C6FF-81A4
person.identifier.orcid0000-0003-3735-6951
person.identifier.orcid0000-0002-8665-5280
person.identifier.ridI-5949-2013
person.identifier.scopus-author-id14832459200
person.identifier.scopus-author-id6602648497
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication5746ab3e-8ffe-4e26-9a41-8392cf031f28
relation.isAuthorOfPublicationf58280c8-298b-4e4c-9f7c-4517300d3382
relation.isAuthorOfPublication.latestForDiscovery5746ab3e-8ffe-4e26-9a41-8392cf031f28

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