RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

Journal Article · Fri Feb 01 00:00:00 EST 2013 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2012.11.029· OSTI ID:22216052

Sá-Júnior, Paulo Luiz de ^[1]; Pasqualoto, Kerly Fernanda Mesquita ^[2]; Ferreira, Adilson Kleber ^[1]; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre de ^[2]; Câmara, Diana Aparecida Dias; Pereira, Alexandre; Madeiro de Souza, Dener ^[1]

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1. Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil)
2. Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil)

Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Capsaicin, which is the primary pungent compound in red peppers, was reported to selectively inhibit the growth of a variety tumor cell lines. Here, we report for the first time a novel synthetic capsaicin-like analogue, RPF101, which presents a high antitumor activity on MCF-7 cell line, inducing arrest of the cell cycle at the G2/M phase through a disruption of the microtubule network. Furthermore, it causes cellular morphologic changes characteristic of apoptosis and a decrease of Δψm. Molecular modeling studies corroborated the biological findings and suggested that RPF101, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. All these findings support the fact that RPF101 is a promising anticancer agent. -- Highlights: ► We report for the first time that RPF101 possesses anticancer properties. ► RPF101 induces apoptosis of human breast cancer cells. ► RPF 101 decreases mitochondrial potential and induces DNA fragmentation.

• OSTI ID: 22216052
• Journal Information: Toxicology and Applied Pharmacology, Vol. 266, Issue 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL CYCLE
DNA
MAMMARY GLANDS
MICROTUBULES
MITOCHONDRIA
NEOPLASMS
PEPPERS
TOXICITY
TUMOR CELLS