punicalagin and Lung-Neoplasms

Lung cancer is a noxious disease with substandard overall survival. Despite this, there are several treatment strategies for lung cancer include chemotherapy, radiotherapy, surgery; however, the overall survival remains poor. Punicalagin has been documented as a potential phytomedicine to selectively inhibit the progression and expansion of numerous cancers. In the present study, we evaluated the antiproliferative ability of punicalagin against lung cancer A549 cells by inducing apoptosis by inhibiting STAT-3 activation. Punicalagin induces toxic effects of A549 cells in a dose-associated manner after 24 h treatment. And we also observed that punicalagin (10, 20, and 30 μM) induced reactive oxygen species generation, alters the mitochondrion membrane potential and apoptotic morphological changes in A549 cells. The STAT-3 overexpression regulates apoptosis, proliferation, and angiogenesis. Here, the punicalagin inhibited STAT-3 translocation and thereby induces apoptosis by inhibiting expression Bcl-2 and enhanced expression of Bax, cytochrome-c, caspase-9, and caspase-3 in A549 cells. Hence, we stated that the punicalagin is a possible therapy for non-small cell lung, malignancies. Altogether, the punicalagin is a promising phytomedicine in malignancy treatment and further endeavors are needed to unveil the complete potential.

Topics: A549 Cells; Apoptosis; Humans; Hydrolyzable Tannins; Lung Neoplasms; Neoplasm Proteins; Protein Transport; Reactive Oxygen Species; STAT3 Transcription Factor

Lung cancer is the most common cause of cancer-related deaths worldwide. Punicalagin is an ellagitannin mostly found in pomegranate husk and shows very strong antitumoral activity. The purpose of this study was to investigate the mechanism in which punicalagin acts as an antiproliferative agent on A549 cell line (adenocarcinomic human alveolar basal epithelial cells) and MRC-5 cell line (normal lung fibroblast cells). The cultured cells were treated with punicalagin at concentrations of 1-100 μM for 24 h. For this aim, cell growth inhibition, percentage of apoptotic cells, cell cycle distribution, morphological changes, cellular and mitochondrial reactive oxygen species (ROS) production, and expression of apoptotic proteins were evaluated. Cell viability test and morphological examinations showed that punicalagin at 50 and 75 µM concentrations exhibited toxic effect against lung cancer cells but not toxic against normal lung cells. Cytoplasmic ROS production decreased with the application of punicalagin, while the level of ROS released from mitochondria increased due to mitochondrial dysfunction. Studies of apoptosis indicated that both punicalagin concentrations induced apoptotic process in A549 cells. However, cell cycle was arrested in the G1/S phase after punicalagin treatment. These findings suggest that punicalagin has antiproliferative and apoptotic properties in these concentrations.

Topics: A549 Cells; Apoptosis; Cell Line, Tumor; Cell Survival; Humans; Hydrolyzable Tannins; Lung Neoplasms; Membrane Potential, Mitochondrial; Mitochondria; Reactive Oxygen Species

Most conventional treatments on non-small cell lung carcinoma always accompany with awful side effects, and the incidence and mortality rates of this cancer are increasing rapidly worldwide. The objective of this study was to examine the anticancer effects of extract of Punica granatum (pomegranate) leaves extract (PLE) on the non-small cell lung carcinoma cell line A549, H1299 and mouse Lewis lung carcinoma cell line LL/2 in vitro, and explore its mechanisms of action. Our results have shown that PLE inhibited cell proliferation in non-small cell lung carcinoma cell line in a concentration- and time-dependent manner. Flow cytometry (FCM) assay showed that PLE affected H1299 cell survival by arresting cell cycle progression in G2/M phase in a dose-dependent manner and inducing apoptosis. Moreover, PLE could also decrease the reactive oxygen species (ROS) and the mitochondrial membrane potential (ΔYm), indicating that PLE may induce apoptosis via mitochondria-mediated apoptotic pathway. Furthermore, PLE blocked H1299 cell migration and invasion, and the reduction of matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed in vitro. These results suggested that PLE could be an effective and safe chemotherapeutic agent in non-small cell lung carcinoma treatment by inhibiting proliferation, inducing apoptosis, cell cycle arrest and impairing cell migration and invasion.

Topics: Animals; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Shape; Cell Survival; Chlorocebus aethiops; Ellagic Acid; HEK293 Cells; Humans; Hydrolyzable Tannins; Linear Models; Lung Neoplasms; Lythraceae; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Membrane Potential, Mitochondrial; Mice; Mitochondria; Neoplasm Invasiveness; Plant Extracts; Plant Leaves; Reactive Oxygen Species; Signal Transduction; Vero Cells