Xanthohumol Induces Different Cytotoxicity and Apoptotic Pathways in Malignant and Normal Astrocytes

Abstract

Cytotoxicity and the mechanisms of cell death induced by xanthohumol (XN) were compared in normal and cancerous human cells as the differences may be relevant for the potential use of XN in cancer therapy. The cancer cells seemed to be more susceptible to the cytotoxicity of XN than normal cells, but a significant difference was observed only in astrocytic cells. XN induced a higher rate of apoptosis in glioblastoma cells than in normal astrocytes, which was associated with activation of p53 and an elevated Bax/Bcl-2 ratio in glioblastoma cells, indicating an intrinsic caspase-dependent apoptotic pathway. In contrast, a reduced Bax/Bcl-2 ratio was observed in normal human astrocytes. This was also associated with higher expression of the cell cycle inhibitor, p21, in glioblastoma cells than in normal astrocytes. In addition, at a lower, non-cytotoxic concentration, XN partially inhibited the invasiveness of glioblastoma cells. Due to the selective sensitivity of astrocytic cells to XN, this compound should be studied further as a candidate for adjuvant therapy in the treatment of glioma.

Dose-Dependent Protective and Inductive Effects of Xanthohumol on Oxidative DNA Damage in Saccharomyces cerevisiae

“…The capacity of xanthohumol to induce intracellular ROS was shown to activate the mitochondrial apoptotic pathway in human malignant glioblastoma cells (9). Other studies support this fi nding, showing that it is able to inhibit the growth and to induce apoptosis in several cancer cell lines: prostate (10), ovarian (11), glioblastoma and malignant astrocytes (9,12), lymphocytic leukaemia (13) and colon (14).…”

“…Anticarcinogenic and antioxidant properties of xanthohumol present in Humulus lupulus L. have been reported before (3,5,(9)(10)(11)(12)(13)(14)(37)(38)(39). However, scarce information is available on the eff ect of xanthohumol on yeast cells.…”

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

“…These results are in accordance with those reported by Pan et al (27), which demonstrated that xanthohumol induces apoptosis of human colon cancer cells via caspase-3, -8 and -9. Furthermore, Zajc et al (15) reported that xanthohumol induces different cytotoxic and apoptotic pathways via Bax/Bcl-2 in malignant and normal astrocytes. Kunnimalaiyaan et al (28) demonstrated that xanthohumol inhibits induces apoptosis via the anti-apoptotic markers, survivin, cyclin D1 and Mcl-1, in hepatocellular carcinoma.…”

“…Recent studies investigating xanthohumol have predominantly focused on the prevention and treatment of cancer (13,14). Studies have demonstrated that xanthohumol inhibits tumor cell growth of colon cancer, prostate cancer, cervical cancer, liver cancer and leukemia cells (15)(16)(17). Therefore, the aim of the present study was to investigate the effect of xanthohumol on the proliferation of human laryngeal squamous cell carcinoma.…”

Study of Electrochemical Oxidation of Xanthohumol by Ultra-Performance Liquid Chromatography Coupled to High Resolution Tandem Mass Spectrometry and Ion Mobility Mass Spectrometry

“…In the past few years, the brewing industry has been interested in producing XN-enriched beers, mainly due to the recognized health benefits. XN possesses a large spectrum of chemopreventive mechanisms in a wide variety of cancers, such as breast [4], colon [5], colorectal [6], brain [7], ovarian [8], leukemia [9,10] and prostate [11][12][13] cancer, with no effects on major organ functions after oral administration [14]. A recent study reported that XN-supplemented beer helps reducing inflammation, oxidative stress and angiogenesis, ameliorating the wound healing process [15].…”