Phillygenin Exerts In Vitro and In Vivo Antitumor Effects in Drug-Resistant Human Esophageal Cancer Cells by Inducing Mitochondrial-Mediated Apoptosis, ROS Generation, and Inhibition of the Nuclear Factor kappa B NF-κB Signalling Pathway

Abstract

Background Esophageal cancer causes considerable mortality and is ranked as the 6 th most prevalent type of cancer across the world. At present, there is no effective esophageal cancer chemotherapy without adverse effects. Moreover, emergence of drug resistance among cancer is another obstacle in the treatment of esophageal cancer. Novel molecules of plant origin may prove beneficial in the development of chemotherapy for esophageal carcinoma. In this study we examined the anticancer effects of phillygenin against the vindesine-resistant esophageal cancer cell line SH-1-V1. Material/Methods The proliferation rate of SH-1-V1 cells was determined by WST-1 assay. Apoptosis was confirmed by propidium iodide (PI) staining. Cell cycle analysis, ROS, and MMP determination were performed by flow cytometery. Protein expression was assessed by Western blot analysis. Results We found that phillygenin inhibited the growth of SH-1-V1 cells and exhibited an IC 50 of 6 μM. Investigation of the underlying mechanism revealed that phillygenin triggered apoptotic cell death of the SH-1-V1 cells, which was also associated with enhancement of Bax expression and decreased expression of Bcl-2. Moreover, the expression of cleaved caspase 3 and 9 also increased upon phillygenin treatment. Phillygenin also caused a significant increase in ROS production, concomitant with decreased MMP levels. Phillygenin also caused arrest of cells in the G2/M phase of the cell cycle. In vivo evaluation of phillygenin revealed that it can inhibit tumor weight and volume, suggesting the anticancer potential of phillygenin. Conclusions In brief, phillygenin inhibited in vitro and in vivo cancer cell growth in drug-resistant human esophageal cancer cells, and these effects were mediated via apoptosis, ROS generation, mitochondrial membrane potential loss, and activation of the NF-κB signalling pathway.

Targeting Cancer Metabolism to Resensitize Chemotherapy: Potential Development of Cancer Chemosensitizers from Traditional Chinese Medicines

“…Phillygenin is a plant-derived tetrahydrofurofuran lignan. He et al reported that it could inhibit the in vitro and in vivo growth of vindesine-resistant esophageal cancer cells via inducing ROS generation and apoptosis [121]. As a natural product derived from bees, propolis was commonly used for a long time due to its various bioactivities.…”

Anticancer activity of Callicarpa arborea Roxb. extracts against Type-II human lung adenocarcinoma cell line, A549

“…induced cytotoxic effects in cancer cells by increasing ROS production. Bioactive compounds such as phillygenin and plumbagin which are isolated from plants also induced cell death in cancer cells through the generation of intracellular ROS, resulting in apoptosis via a p53 dependent pathway (De et al, 2019;He et al, 2019). Understanding the nature of cell death induced by CACE and the mechanisms involved would be the next important step.…”

Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer

“…The anticancer effects of polyphenols depend not only on their chemical structure and concentration but also on the type of cancer. Lignans considered to be phytoestrogens are bioactive compounds exhibiting various anticancer properties, such as apoptosis induction and tumor growth reduction (15). Xanthones, such as α-mangostin, mediate cytotoxicity mainly via cell cycle arrest and reactive oxygen species (ROS)-induced apoptosis (16).…”