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
Authors: Yiling Wang
Qingbo Yang
Jiantao He
Wei Wei
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: Esophageal cancer; chemotherapy; drug resistance; phillygenin; vindesine-resistant
Affiliations: Department of Thoracic Surgery, Shanghai Tenth People's Hospital, Shanghai, China (mainland)., Department of Emergency, Shanghai Tenth People's Hospital, Shanghai, China (mainland).

Abstract:  BACKGROUND Esophageal cancer causes considerable mortality and is ranked as the 6th 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 AND 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 IC50 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-kB signalling pathway. 

Retracted: Yes

PubPeer comments:
 Figure 3.  Phillygenin triggers apoptotic cell death of SH-1-V1 cells, as depicted by propidium iodide staining . Multiple copies of cells suggest that the images are composites. ![file] , 
 Figure 8.  Effect of phillygenin on the expression of NF-kB expression. ![file] NF-kB band is unexpectedly similar to the Bcl-2 bands in *[left]* Figure 5 from [Luo et al (2019)] .  Effect of ferruginol on the expression apoptosis associated proteins as depicted by the western blot analysis . *[right]* Figure 6 from [Zhang et al (2019)] .  Effect of Trifolirhizin on the expression of Bax and Bcl-2 proteins as depicted by western blot analysis. The image shows that Trifolirhizin increased Bax and decreased Bcl-2 expression. ![file] Here the same bands appear in a broader context: Figure 3 from [Zhou Hu (2018)] .  Effect of different concentrations of Evodiamine on the protein expression of apoptosis-related proteins as determined by Western blotting. Other manifestations are linked in that thread. ![file] , 
 Retracted [25 March 2021] .  An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. ,