Licochalcone A induces apoptosis in KB human oral cancer cells via a caspase-dependent FasL signaling pathway

Abstract

Licochalcone A (Lico-A) is a natural phenol licorice compound with multiple bioactivities, including anti-inflammatory, anti-microbial, anti-fungal and osteogenesis-inducing properties. In the present study, we investigated the Lico-A-induced apoptotic effects and examined the associated apoptosis pathway in KB human oral cancer cells. Lico-A decreased the number of viable KB oral cancer cells. However, Lico-A did not have an effect on primary normal human oral keratinocytes. In addition, the IC50 value of Lico-A was determined to be ~50 μM following dose-dependent stimulation. KB oral cancer cells stimulated with Lico-A for 24 h showed chromatin condensation by DAPI staining, genomic DNA fragmentation by agarose gel electrophoresis and a gradually increased apoptotic cell population by FACS analysis. These data suggest that Lico-A induces apoptosis in KB oral cancer cells. Additionally, Lico-A-induced apoptosis in KB oral cancer cells was mediated by the expression of factor associated suicide ligand (FasL) and activated caspase-8 and −3 and poly(ADP-ribose) polymerase (PARP). Furthermore, in the KB oral cancer cells co-stimulation with a caspase inhibitor (Z-VAD-fmk) and Lico-A significantly abolished the apoptotic phenomena. Our findings demonstrated that Lico-A-induced apoptosis in KB oral cancer cells involves the extrinsic apoptotic signaling pathway, which involves a caspase-dependent FasL-mediated death receptor pathway. Our data suggest that Lico-A be developed as a chemotherapeutic agent for the management of oral cancer.

Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells

“…To determine the cellular signaling pathway of Lico-A induced TRAIL expression in FaDu cancer cells, we examined the activation of mitogen-activated protein kinase (MAPK) signaling pathways that have previously been linked to Lico-A-mediated TRAIL expression in the KB human oral cancer cell line (Kim et al, 2014). As shown in Fig.…”

“…Treatment with 100 and 125 µM Lico-A decreased FaDu cell viability by 50% and 80%, respectively, compared to the non-treated control. Although Zheng et al, reported that the IC 50 value of Lico-A was estimated at approximately 300 µM in the human oral cancer SCC-25 cells (Zeng et al, 2014), the IC 50 value of Lico-A in FaDu cells was estimated at approximately 100 µM, a higher IC 50 value than the 50 µM IC 50 reported for KB human oral cancer cells (Kim et al, 2014). However, IC 50 values of Lico-A was estimated at various dose ranges in other cancer cells.…”

“…According to recent studies, Lico-A has antioxidant (Fu et al, 2013), antiviral (Adianti et al, 2014), anti-inflammatory (Chu et al, 2012; Fu et al, 2013), antimicrobial (Messier and Grenier, 2011), antimalarial (Mishra et al, 2009), antiangiogenic (Kim et al, 2010), and osteogenic activities (Kim et al, 2012). Furthermore, Lico-A reportedly has anticancer activity in various cancers types such as oral (Kim et al, 2014), bladder (Yuan et al, 2013), ovarian (Lee et al, 2012), gastric (Xiao et al, 2011), colon (Lee et al, 2008), and prostate (Fu et al, 2004; Yo et al, 2009) cancer as well as in hepatocellular carcinoma (Choi et al, 2014). Although the antitumor effects and cellular mechanism of Lico-A activity have been investigated in various cancers, little is known regarding its effect on HNSCC.…”

Chemopreventive Effects of Licorice and Its Components

“…LicA decreased the viability of KB human oral cancer cells but had no effect on primary normal human oral keratinocytes [90]. LicA appeared to act by inducing apoptosis that was mediated by the expression of factor associated suicide ligand (FasL) and activated caspases 8 and 3 and PARP [90].…”

Licochalcone A Induced Suicidal Death of Human Erythrocytes

“…Licochalcone A, an anti-inflammatory [1][2][3][4], immunomodulatory [5,6], and antimicrobial [3,5,[7][8][9] polyphenol extracted from Glycyrrhiza inflata [1][2][3]10], triggers apoptosis or inhibits proliferation and migration of tumor cells [11], including those of cervical cancer [12], oral squamous carcinoma [7,9,[13][14][15], esophageal carcinoma [16], gastric cancer [4,17,18], hepatocellular carcinoma [2,19], malignant pleural mesothelioma [20], bladder determined photometrically at 405 nm. The absorption of the supernatant of erythrocytes lysed in distilled water was defined as 100% hemolysis.…”