Resveratrol induces apoptotic cell death in rat H4IIE hepatoma cells but necrosis in C6 glioma cells

Michels, G.; Wätjen, Wim; Weber, Nadine; Niering, Petra; Chovolou, Yvonni; Kampkötter, Andreas; Proksch, Peter; Kahl, Regine

doi:10.1016/j.tox.2006.05.014

Cited by 55 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it was Sun et al (24) who provided the direct evidence that resveratrol up-regulated the apoptotic signaling pathway during its cytotoxic effects in H22 hepatoma cells. Furthermore, support for the involvement of the apoptotic pathway as the primary cytotoxic mechanism underlying resveratrol's anticancer effect was demonstrated in H4IIE cells (25). The activation of the p53 pathway upon resveratrol treatment as observed in the present study is in agreement with an earlier report (26).…”

Section: Discussionsupporting

confidence: 93%

Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats

et al. 2011

View full text Add to dashboard Cite

Abstract. Resveratrol, a phytochemical compound abundant in red wine and grapes, is known to affect cancer cells both in vitro and in vivo. A great amount of data have indicated the therapeutic benefits of resveratrol against cancer. However, it remains unclear whether these benefits are similar and equally effective in both the early and advanced stages of cancer or carcinogenesis. In this study, we report the effects of resveratrol in the early and advanced stages of hepatocarcinogenesis in a model of N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) of male Wistar rats. For the experiment, rats were divided into different groups and treated with resveratrol either from day 1 of DEN administration for 15 days (pre-HCC), or after the development of HCC, i.e., 15-16 weeks after DEN administration (post-HCC), and compared to untreated HCC-bearing rats. Biochemical analysis of α-fetoprotein, the known serum marker for HCC, and other serum and liver marker enzymes also demonstrated a decreased level upon resveratrol treatment compared to the untreated HCC-bearing rats. H&E staining of tissue sections from the liver showed alteration or transformation of liver parenchymatous tissue in DEN-induced HCC (at 15-16 weeks). Resveratrol treatment during early (on day 1 of DEN-induction) and advanced (weeks 17-18) HCC showed a marked difference in the tissue architecture compared to untreated HCC. Immunoblot analysis revealed that resveratrol intervention at both the early and advanced stages of DEN-induced HCC activated the apoptotic markers, such as PARP cleavage, caspase-3 activation, p53 up-regulation and cytochrome-c release. In addition, semiquantitative RT-PCR and immunoblot analysis demonstrated the up-and downregulation of key apoptotic regulators, such as Bax and Bcl 2 , respectively, in a resveratrol treatment-dependent manner. Our results indicate that the administration of resveratrol either at the early or advanced stages of hepatocarcinogenesis is equally effective and involves the activation of the apoptotic pathway in male Wistar rats.

show abstract

Section: Discussionsupporting

confidence: 93%

Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Resveratrol is a member of the phytoalexin family, which are low molecular weight, secondary metabolites produced by plants as a defensive mechanism against certain stresses, such as attack by pathogens, wounds and ultraviolet irradiation. Numerous studies in the literature have indicated that resveratrol exhibits anticancer, anti-inflammatory, anti-oxidative and antiasthmatic effects (26,27,35,36), suppresses metastasis in several cancers (37), inhibits platelet aggregation in cardiovascular diseases, and regulates mucin, inflammatory mediators [monocyte chemoattractant protein-1, interleukin (IL)-6 and IL-8] and matrix-metalloprotease-9 expression in chronic obstructive pulmonary disease (38)(39)(40). Another study revealed that resveratrol inhibits the Hh signaling pathway in prostate cancer (32).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis

et al. 2015

View full text Add to dashboard Cite

Abstract. The hedgehog (Hh) signaling pathway is vital to vertebrate development, the homeostatic process and tumorigenesis. Epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, which in turn promotes cancer metastasis and invasion. Resveratrol is a natural polyphenolic compound found in grapes, a variety of berries, peanuts and other plants. Numerous studies have demonstrated that the Hh signaling pathway is able to regulate the EMT, and that resveratrol can suppress carcinoma invasion and metastasis. In addition, certain studies have indicated that resveratrol can inhibit the Hh signaling pathway and EMT in cancers other than gastric cancer. The purpose of the present study was to investigate the inhibitory effect of resveratrol on the Hh signaling pathway and EMT in gastric cancer in vitro. Gastric cancer SGC-7901 cells were treated with resveratrol or cyclopamine at different concentrations. The viability of the cells was assessed using an MTT assay. The expression of Gli-1, a key component of the Hh signaling pathway, and Snail, E-cadherin and N-cadherin, key components of EMT, was detected by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The invasion and metastasis of the cells were observed by performing a cell scratch test. The RT-PCR and western blotting showed a decrease in Gli-1, Snail and N-cadherin expression, and an increase in E-cadherin expression in the resveratrol and cyclopamine group compared with the control group, suggesting that resveratrol inhibited the Hh pathway and EMT, as did cyclopamine. The MTT assay indicated that the viability of the SGC-7901 cells was significantly decreased in a concentration-dependent manner following resveratrol and cyclopamine treatment. The cell scratch test showed slower cell invasion and metastasis in the resveratrol and cyclopamine groups. These findings indicated that resveratrol was able to inhibit the Hh signaling pathway and EMT, and suppress invasion and metastasis in gastric cancer in vitro.

show abstract

“…The increase of fluorescence was analysed for 3 h. We further investigated nuclear fragmentation (Hoechst 33342 staining) as a further feature of apoptotic cell death, as well as ethidium bromide/acridine orange staining as feature of necrotic cell death according to Michels et al 22 . The apoptotic/necrotic index (defined as percentage of cells with fragmented nuclei/ethidium bromide staining in a randomly selected visual field) was determined by analysing three cell culture dishes for each measurement (four visual fields counted per dish) in triplicate.…”

Section: Resultsmentioning

confidence: 99%

Prenylated flavanone derivatives isolated from Erythrina addisoniae are potent inducers of apoptotic cell death

et al. 2015

View full text Add to dashboard Cite

Extracts of Erythrina addisoniae are frequently used in the traditional medicine of Western Africa, but only insufficient information about active compounds is available. From the stem bark of Erythrina addisoniae, three new (1, 2, 4) and three known (3, 5, 6) flavanones were isolated: addisoniaflavanones I and II, containing either a 2´´,3´´-epoxyprenyl moiety (1) or a 2´´,3´´-dihydroxyprenyl moiety (2) were shown to be highly toxic (MTT-assay: EC 50 -values of 5.25 +/-13.5 and 8.5 +/-15.2 µM, respectively) against H4IIE hepatoma cells. The cytotoxic potential of the other isolated flavanones was weaker (range of EC 50 -values between 15 and >100 µM). Toxic effects of addisoniaflavanone I and II were detectable after 3 h (MTT assay). Both compounds induced an apoptotic cell death (caspase 3/7 activation, nuclear fragmentation) in the hepatoma cells and, at high concentrations, also necrosis (membrane disruption: ethidium bromide staining), Formation of DNA strand breaks was not detectable after incubation with these compounds (comet assay). In conclusion, the new prenylated flavanones addisoniaflavanones I and II may be of interest for pharmacological purposes (e.g. potential use as cytostatic drugs) due to their high cytotoxic and pro-apoptotic potential.

show abstract

Resveratrol induces apoptotic cell death in rat H4IIE hepatoma cells but necrosis in C6 glioma cells

Cited by 55 publications

References 32 publications

Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats

Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats

Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis

Prenylated flavanone derivatives isolated from Erythrina addisoniae are potent inducers of apoptotic cell death

Contact Info

Product

Resources

About