Abstract
Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant to identify novel drugs that can improve the treatment options for lung cancer. Natural products have been an important source for the discovery of new compounds with pharmacological potential including antineoplastic agents. We have previously isolated a prenylated benzophenone (7-epiclusianone) from Garcinia brasiliensis (Clusiaceae) that has several biological properties including antiproliferative activity against cancer cell lines. In continuation with our studies, the present work aimed to investigate the mechanisms involved with antiproliferative activity of 7-epiclusianone in A549 cells. Our data showed that 7-epiclusianone reduced the viability of A549 cells in a concentration-dependent manner (IC50 of 16.13 ± 1.12 μM). Cells were arrested in G1/S transition and apoptosis was induced. In addition, we observed morphological changes with cytoskeleton disorganization in consequence of the treatment. Taken together, the results showed that cell cycle arrest in G1/S transition is the main mechanism involved with antiproliferative activity of 7-epiclusianone. Our results are promising and open up the prospect of using this compound in further anticancer in vivo studies.
Highlights
Lung cancer is the leading cause of cancer deaths in the world [1] and can be divided in two main forms: non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), which represent, respectively, 85% and 15% of all diagnosed lung cancers [2]
7-Epiclusianone was isolated from ethanolic extract from fruit epicarps of G. brasiliensis by successive chromatographic steps and characterized by Nuclear Magnetic Resonance (NMR) and MS spectral analysis
Different dilutions of this compound were used to treat A549 lung cancer cells, and we found antiproliferative and pro-apoptotic effects in a concentration-dependent manner
Summary
Lung cancer is the leading cause of cancer deaths in the world [1] and can be divided in two main forms: non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), which represent, respectively, 85% and 15% of all diagnosed lung cancers [2]. NSCLC is composed of three histological subtypes: squamous cell carcinomas (SSCs), lung adenocarcinoma and large-cell lung carcinoma (LCLC). Among these subtypes, adenocarcinoma is the most prevalent [3]. A cell line derived from human lung cancer (A549) was used as a model to investigate the influence of 7-epiclusianone on cell cycle progression, apoptosis induction and cytoskeleton network. Our data open up the prospect of using 7-epiclusianone as a scaffold for the design of novel and selective drug candidates for further in vivo studies and it is a promising tool for the development of new therapeutic agents for lung cancer treatment
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