title: 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.
abstract: 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.
authors.affiliation: Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo, Brazil.
authors.forename: Paulo Luiz
authors.initials: PL
authors.lastname: de-Sá-Júnior
authors.forename: Kerly Fernanda Mesquita
authors.initials: KF
authors.lastname: Pasqualoto
authors.forename: Adilson Kleber
authors.initials: AK
authors.lastname: Ferreira
authors.forename: Maurício Temotheo
authors.initials: MT
authors.lastname: Tavares
authors.forename: Mariana Celestina Frojuello Costa Bernstorff
authors.initials: MC
authors.lastname: Damião
authors.forename: Ricardo Alexandre
authors.initials: RA
authors.lastname: de Azevedo
authors.forename: Diana Aparecida Dias
authors.initials: DA
authors.lastname: Câmara
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pereira
authors.forename: Dener Madeiro
authors.initials: DM
authors.lastname: de Souza
authors.forename: Roberto
authors.initials: R
authors.lastname: Parise Filho
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation; D005260:Female; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular
chemical_list: D002211:Capsaicin