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

Abstract

BackgroundBeta-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/MethodsCCK-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.ResultsThe 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.ConclusionsThe 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.

Reprogramming of erythrocyte lifespan by NFκB‐TNFα naphthoquinone antagonist β‐lapachone is regulated by calcium overload and CK1α

“…Intriguingly, these quinones, along with emodin (Mischitelli et al, 2016b) and NSC-95397 (Mischitelli et al, 2016a), cause redox imbalance in RBCs, which LAP does not (Figure 5). This is in contrast to the oxidative properties of LAP observed in nucleated cells (Bey et al, 2007;Han et al, 2019;Li et al, 2014;Park et al, 2011;Torrente et al, 2020), which may be accounted for by differences in metabolic demands between normal and cancer cells. Notably, we have previously shown that N,N-diethyl-3-methylbenzamide (DEET) and triclosan, two other pro-eryptotic compounds, similarly do not elicit oxidative stress in RBCs .…”

“…pyran-5,6-dione, C 15 H 14 O 3 ; LAP), a naphthoquinone that naturally occurs in extracts of Lapacho tree (Lamberti et al, 2013) (Figure 1a), possesses an antitumor activity in vitro and in vivo (Ferraz da Costa et al, 2020). Particularly, LAP has been shown to inhibit colon, prostate, nasopharyngeal, melanoma, hepatocellular, breast, glioma, lung, and pancreatic cancer growth (Bey et al, 2007;Han et al, 2019;Lamberti et al, 2013;Li et al, 2014;Park et al, 2011;Silvers et al, 2017;Yang et al, 2017).…”

Cytotoxicity assessment of beta-lapachone in endothelial cells

“…BLP effectively inhibited the growth of oral squamous cell carcinoma of the HN22 and HSC4 lines by promoting the DNA condensation and formation of apoptotic bodies in the cell nucleus (Jeon et al, 2015). This substance induced autophagy and suppressed the migration and invasion of HNE1 nasopharyngeal carcinoma cells (Han, Shi, & Li, 2019). In addition to the studies regarding human species, the cytotoxic action of this substance has recently been demonstrated in canine osteosarcoma cells (Cruz et al, 2018).…”

Autophagy-related signaling pathways are involved in cancer (Review)

“…It has been demonstrated that the mTOR/PI3K/Akt signaling pathway is triggered in tumor cells and is considered to be a key therapeutic target for the treatment of various cancer types ( 48 ). Han et al ( 49 ) demonstrated that β-rapazone may block the mTOR/PI3K/Akt signaling pathway, induce autophagy, and ultimately inhibit the migration and invasion of nasopharyngeal carcinoma cells. In addition, angiogenesis may provide nutrition and oxygen to tissues, which are essential for tumor growth and metastasis.…”