Abstract

Purpose: To investigate the capacity of aqueous Pseuderanthemum paltiferum leaf extracts (PPA) to induce apoptosis in A549 human lung cancer cells and the possible mechanisms of action. Methods: Human lung cancer A549 cells were cultured in the presence of PPA (0 - 1000 μg/mL). Cell viability was assessed by MTT assay while morphological alterations in the cells were observed by Hoechst 33342/PI double staining. Intracellular reactive oxygen species (ROS) levels and subsequent changes of mitochondrial membrane potential were also investigated. Involvement of caspase-3 activation in the apoptotic pathway was determined. Results: PPA inhibited the growth of A549 cells in a concentration- and time-dependent manner. Major phenotypic apoptotic cell death was evidenced in microscopic images. Furthermore, treatment of A549 cells with PPA resulted in a significant increase in the production of ROS accompanied by attenuation of mitochondrial membrane potential, thus inducing the activation of caspase-3 activity ( p < 0.05). Conclusion: PPA exerts anti-cancer activity by suppression of cell viability and induction of ROSmediated mitochondrial dependent apoptosis in A549 cells, and may be a potential candidate for the development of a therapeutic agent for lung cancer. Keywords: Pseuderanthemum palatiferum , Apoptosis, Reactive oxygen species, Mitochondria, Lung cancer

Highlights

  • Lung cancer causes significant devastating morbidity and mortality among men and women worldwide [1]

  • The disruption of membrane potential (MMP) plays a major role in the apoptosis mechanism we examined, by Tetramethyl rhodamine ethyl ester (TMRE) assay, whether Pseuderanthemum paltiferum leaf extracts (PPA) mediated A549 cell

  • Since the increased levels of active caspase-3 are consistent with luminescence assay, our results suggested the role of PPA induced apoptosis in human lung cancer A549 cells was dependent on the activation caspase-3

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Summary

Introduction

Lung cancer causes significant devastating morbidity and mortality among men and women worldwide [1]. It is clinically categorized into small cell and non-small cell lung cancer (NSCLC) subtypes. Incidence of non-small cell lung cancer (NSCLC) revealed nearly 80 % among other subtypes. Cisplatin (cis-diamminedichloroplatinum (II); CDDP) and CDDP-based combinations have been the first line chemotherapeutic agents targeting NSCLC. New approaches are needed for the development of therapeutic drugs with low toxicities and fewer side effects to overcome cancer more effectively. A large number of anti-cancer therapeutic agents derived from plant sources have been found to be potent in the treatment and prevention of cancers [5,6]

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