Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Abstract

Abstract. Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required.

Anticancer Activity and Mechanism of Xanthohumol: A Prenylated Flavonoid From Hops (Humulus lupulus L.)

“…It has been reported that Xn treatment reduced the cell viability of LSCC cells (RK33 and RK45), but had very low or no toxicity in normal cells (rat oligodendroglia-derived cells, OLN-93 and human skin fibroblasts, HSF) ( Slawinska-Brych et al, 2015 ). Moreover, Xn exhibited potent cytotoxicity in SCC4 cells, which may be associated with suppression on Mcl-1 and Bcl-2 expression, as well as PARP, p53, and AIF activation ( Li et al, 2016 ). Although changes in these protein expressions or activities have been observed upon Xn treatment, lack of knockdown or overexpression methods to further determine the molecular target of Xn in LSCC.…”

Hop-derived Xanthohumol Induces HL-60 Leukemia Cells Death

“…Hop plant cones contain prenylated flavonoids among which XN have been shown to have cytotoxic effects and to modulate carcinogenesis [39][40]41]. Numerous studies analyzing biological activity showed that XN is antiproliferative and antitumor [42][43][44]41]. The mechanisms through which XN exerts its antitumor properties includes inhibition of alkaline phosphates and upregulation of cell cycle genes in the G0/G1 phase including p21 [40,44].…”

Modulation of Adenosine Receptors by Hops and Xanthohumol in Cell Cultures

“…76,77 The same proapoptotic effect was observed in Ca Ski, 78 LNCaP, 79 and SCC4 cells. 80 However, XN was unable to exhibit antioxidant effects probably as a consequence of an increase in ROS as it has been described in human glioblastoma cells T98G. 75 There are few published studies about the neuroprotective capacity of XN.…”