ABSTRACT
The down-regulation or loss of epithelial markers is often accompanied by the up-regulation of mesenchymal markers. E-cadherin generally suppresses invasiveness, whereas N-cadherin promotes invasion and metastasis in vitro. The aim of this work is to investigate the role of biflorin, a naphthoquinone with proven anticancer properties, on the expression of N-cadherin and AKT proteins in MDA-MB-435 invasive melanoma cancer cells after 12h of exposure to 1, 2.5 and 5 µM biflorin. Biflorin inhibited MDA-MB-435 invasion in a dose-dependent manner (p<0.01). Likewise, biflorin down-regulated N-cadherin and AKT-1 expression in a dose-dependent manner. Biflorin did not inhibit the adhesion of MDA-MB-435 cells to any tested substrates. Additionally, biflorin blocked the invasiveness of cells by down-regulating N-cadherin, most likely via AKT-1 signaling. As such, biflorin may be a novel anticancer agent and a new prototype for drug design.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cadherins/antagonists & inhibitors , Down-Regulation/drug effects , Melanoma/drug therapy , Naphthoquinones/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Signal Transduction/drug effects , Animals , Antineoplastic Agents, Phytogenic/adverse effects , Cadherins/metabolism , Cell Adhesion/drug effects , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Melanocytes/cytology , Melanocytes/drug effects , Melanocytes/metabolism , Melanoma/metabolism , Melanoma/pathology , Mice , Naphthoquinones/adverse effects , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions or infusions of the stem bark of Byrsonima japurensis A. Juss. (Malpighiaceae) are widely used as an anti-inflammatory drug in folk medicine of Amazonas State (Brazil). AIM OF THE STUDY: To evaluate the pharmacological potential of an aqueous extract of the stem bark of Byrsonima japurensis (BJEA) to scientifically verify of its traditional use. MATERIALS AND METHODS: Anti-inflammatory, antihyperalgesic and antiulcer activities were evaluated in Wistar rats, a Hippocratic screening was performed in Swiss mice to evaluate the toxic effects, and antiplatelet evaluation was performed in human platelet rich plasma assay. Additionally, antioxidant activity was evaluated by superoxide radical scavenging method and ß-carotene bleaching test. RESULTS: Anti-inflammatory, antihyperalgesic and gastroprotective activities were observed in rats treated orally with different doses of BJEA. While signals of toxicity were observed in the mice treated with a very high dose of extract (5000mg/kg), no death occurred. BJEA also showed expressive antiplatelet and antioxidant activities in vitro. CONCLUSION: According to our results, it was concluded that stem bark of Byrsonima japurensis has significant and safe anti-inflammatory activity, which is closely related with their potent antioxidant activity, supporting the folk medicinal use of this species.
