Xanthohumol induces apoptosis in cultured 40-16 human colon cancer cells by activation of the death receptor- and mitochondrial pathway

Abstract

Xanthohumol (XN) is one of the major prenylflavonoids found in hop cones (Humulus lupulus L.). In this study, we investigated the cell growth inhibitory potential of XN on cultured human colon cancer cells. Cell proliferation was measured by sulforhodamine B staining. Poly(ADP-ribose)polymerase (PARP) cleavage, activation of caspases-3, -7, -8, and -9, and Bcl-2 family protein expression were detected by Western blot analyses. XN significantly reduced proliferation of the HCT 116-derived colon cancer cell line 40--16. Half-maximal inhibitory concentrations decreased from 4.1 microM after 24 h treatment to 3.6 and 2.6 microM after 48 and 72 h incubation, respectively. Treatment with 15 microM XN for 48 h and with 5 microM for 72 h led to the detection of the cleaved 89 kDa fragment of 116 kDa PARP as an indication of apoptosis induction. Concomitantly, we observed activation and cleavage of the effector caspases-3 and -7, induced by activation of the initiator caspases -8 and -9. Expression of anti-apoptotic Bcl-2 was down regulated when the cells were treated with XN for 48--72 h. We conclude that induction of apoptosis by downregulation of Bcl-2 and activation of the caspase cascade may contribute to the chemopreventive or therapeutic potential of XN.

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.…”

Synthesis and Biological Evaluation of Chalcones Possessing Ring Activating Groups as Potent of Anticancer Agents

“…Some prominent examples of this series of chalcones are Xanthohumol, Butein, Flavokawain A, B and C, Dimethyl amino chalcone etc. [3] Xanthohumol(1), a prenylated chalcone isolated from the hop cones, is suggested to exhibited broad spectrum anticancer properties against different types of human cancer cells like 40-16 human colon cancer cell through inhibition of the proliferation and induction of human cancer cell apoptosis [4,5]. Butein(2), isolated from the stems of Rhus verniciflua, has been shown to inhibit human colon adenocarcinoma cell proliferation and also it induces apoptosis in HL-60 cells [6].…”

“…Other natural chalcones such as Dimethyl amino chalcone(4) and cardamonin (5) have been reported to possess anticancer and anti-inflammatory activities [8]. The anticancer activity of chalcone is believed to be a result of binding to the tubulin assembly and thereby preventing it from polymerisation to microtubule [9].…”

Anti-Invasive and Anti-Angiogenic Effects of Xanthohumol and Its Synthetic Derivatives

“…It has strong anti-proliferative activity against cancer cell lines derived from breast, colon, ovary, and prostate (Miranda et al, 1999;Delmulle et al, 2006). In addition, it has also exhibited chemopreventive effects by inducing apoptosis of cancer cells and anti-initiating properties (Gerhauser et al, 2002;Pan et al, 2005). Furthermore, it has also been reported to inhibit cancer cell invasion (Barbara et al, 2005), inflammation and angiogenesis (Albini et al, 2006;Monteghirfo et al, 2008).…”