Advanced search
Start date
Betweenand
Related content
(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

Full text
Author(s):
Show less -
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
Affiliation:
[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
Abstract

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