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

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 RPF15...

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Bibliographic Details
Published in:Tumor biology 2015-09, Vol.36 (9), p.7251-7267
Main Authors: Ferreira, Adilson Kleber, Tavares, Maurício Temotheo, Pasqualoto, Kerly Fernanda Mesquita, de Azevedo, Ricardo Alexandre, Teixeira, Sarah Fernandes, Ferreira-Junior, Wilson Alves, Bertin, Ariane Matiello, de-Sá-Junior, Paulo Luiz, Barbuto, José Alexandre Marzagão, Figueiredo, Carlos Rogério, Cury, Yara, Damião, Mariana Celestina Frojuello Costa Bernstorff, Parise-Filho, Roberto
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - drug effects
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer Research
Capsaicin - administration & dosage
Capsaicin - analogs & derivatives
Capsaicin - chemistry
Cell Cycle - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Female
Gene Expression Regulation, Neoplastic - drug effects
Herbal medicine
Humans
Mice
Models, Molecular
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
Protein Binding
Proteins
Research Article
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1010-4283
1423-0380
DOI:10.1007/s13277-015-3441-z