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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

RPF151, a novel capsaicin-like analogue: in vitro studies and in vivo preclinical antitumor evaluation in a breast cancer model

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Ferreira, Adilson Kleber [1] ; Tavares, Mauricio Temotheo [2] ; Mesquita Pasqualoto, Kerly Fernanda [3] ; de Azevedo, Ricardo Alexandre [1] ; Teixeira, Sarah Fernandes [1] ; Ferreira-Junior, Wilson Alves [4] ; Bertin, Ariane Matiello [1] ; de-Sa-Junior, Paulo Luiz [5] ; Marzago Barbuto, Jose Alexandre [6] ; Figueiredo, Carlos Rogerio [1] ; Cury, Yara [4] ; Costa Bernstorff Damio, Mariana Celestina Frojuello [2] ; Parise-Filho, Roberto [2]
Total Authors: 13
[1] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Lab Tumor Immunol, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Lab Design & Synth Bioact Subst LAPESSB, Dept Pharm, Fac Pharmaceut Sci, BR-05508000 Sao Paulo, SP - Brazil
[3] Butantan Inst, Biochem & Biophys Lab, Sao Paulo, SP - Brazil
[4] Butantan Inst, Lab Pain & Signaling, Sao Paulo, SP - Brazil
[5] Butantan Inst, Genet Lab, Sao Paulo, SP - Brazil
[6] Univ Sao Paulo, Fac Med, Cell & Mol Therapy Ctr NUCEL NETCEM, Sao Paulo, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: TUMOR BIOLOGY; v. 36, n. 9, p. 7251-7267, SEP 2015.
Web of Science Citations: 10

Capsaicin, the primary pungent component of the chili pepper, has antitumor activity. Herein, we describe the activity of RPF151, an alkyl sulfonamide analogue of capsaicin, against MDA-MB-231 breast cancer cells. RPF151 was synthetized, and molecular modeling was used to compare capsaicin and RPF151. Cytotoxicity of RPF151 on MDA-MB-231 was also evaluated by the 3-{[}4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis, by flow cytometry, and Western blot analysis of cycle-related proteins were used to evaluate the antiproliferative mechanisms. Apoptosis was evaluated by phosphatidyl-serine externalization, cleavage of Ac-YVAD-AMC, and Bcl-2 expression. The production of reactive oxygen species was evaluated by flow cytometry. RPF151 in vivo antitumor effects were investigated in murine MDA-MB-231 model. This study shows that RPF151 downregulated p21 and cyclins A, D1, and D3, leading to S-phase arrest and apoptosis. Although RPF151 has induced the activation of TRPV-1 and TRAIL-R1/DR4 and TRAIL-2/DR5 on the surface of MDA-MB-231 cells, its in vivo antitumor activity was TRPV-1-independent, thus suggesting that RPF151 should not have the same pungency-based limitation of capsaicin. In silico analysis corroborated the biological findings, showing that RPF151 has physicochemical improvements over capsaicin. Overall, the activity of RPF151 against MDA-MB-231 and its lower pungency suggest that it may have a relevant role in cancer therapy. (AU)

FAPESP's process: 13/07273-2 - Rational design and development of new prototypes derived of antitumor phospholipids as potential inhibitors of the enzyme CtP: phosphoethanolamine citidililtransferase and antitumor agents in non-small cell lung cancer
Grantee:Jose Alexandre Marzagão Barbuto
Support type: Regular Research Grants
FAPESP's process: 13/18160-4 - Novel anticancer candidates: design, synthesis, antitumoral activity and mode of action of novel capsaicinoids and capsinoids analogues
Grantee:Roberto Parise Filho
Support type: Regular Research Grants
FAPESP's process: 12/23233-8 - Novel anticancer candidates: synthesis and antitumoral activity of capsaicin-like sulfonate and sulfonamide analogues.
Grantee:Maurício Temotheo Tavares
Support type: Scholarships in Brazil - Master