Inhibition of Nasopharyngeal Carcinoma by Beta-Lapachone Occurs by Targeting the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Pathway, Reactive Oxygen Species (ROS) Production, and Autophagy Induction
Authors: Yongqing Han
Jingao Li
Dayou Shi
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: Beta-lapachone; anti-cancer effects; HNE1 cells; autophagy; mTOR/PI3K/AKT signaling pathway
Affiliations: Department of Oncology, Nanchang University, Nanchang, Jiangxi, China (mainland)., Department of Oncology, Jiujiang First People's Hospital, Jiujiang, Jiangxi, China (mainland)., Department of Radiotherapy, Jiangxi Tumor Hospital, Nanchang, Jiangxi, China (mainland).

Abstract:  BACKGROUND Beta-lapachone has been shown to exhibit potent anti-cancer effects against various cell lines. In the present study, we examined the anti-cancer effects of beta-lapachone, a quinone, against human HNE1 nasopharyngeal carcinoma cells, and also assessed its effects on cellular migration and invasion, autophagy, mTOR/PI3K/AKT signalling pathway, and ROS production. MATERIAL AND METHODS CCK-8 cell counting assay was used to assess cell viability effects after lapachone treatment. Its effects on the mTOR/PI3K/AKT biochemical pathway were examined by Western blot analysis. Transmission electron microscopy was used to study autophagy induced by beta-lapachone. Effects on cell invasion and cell migration were evaluated by Transwell method. RESULTS The results revealed that beta-lapachone suppresses the proliferation of HNE1 cells, with an IC₅₀ of 30 µM. These growth-inhibitory effects of beta-lapachone were found to be dose-dependent. The investigation of the effects of beta-lapachone on the mTOR/PI3KAKT signalling pathway showed that beta-lapachone blocked this pathway in a concentration-dependent manner. Beta-lapachone also inhibited the migration and invasion of HNE1 nasopharyngeal cancer cells, as shown by Transwell assay. The fluorescence microscopy analysis showed that beta-lapachone increased production of reactive oxygen species (ROS), which is also linked with a concentration-dependent decrease in mitochondrial membrane potential (MMP) levels. Electron microscopy analysis showed that beta-lapachone caused the development of the autophagosomes, and the frequency of the autophagosomes increased with increased dosage of beta-lapachone. The beta-lapachone-triggered autophagy was also associated with increased protein levels of LC3 II and decreased levels of p62. CONCLUSIONS The findings of this study suggest that beta-lapachone inhibits the growth of nasopharyngeal cancer cells by promoting autophagy, and it may be useful in cancer drug discovery paradigms. 

Retracted: Yes

PubPeer comments:
 * Funnel plot and Beggeru2019s test showed that there exited significantly publication bias in the meta-analysis for the operative duration of total thyroidectomy * The paper refers **nine times** to  Funnel plot and Beggeru2019s test . No Begger s Test exists. Its use is a recognised indicator that a purported meta-analytical paper was churned out by a papermill. https: retractionwatch.com 2020 08 21 beggers-cant-be-choosers-as-another-meta-analysis-is-retracted ,