Glycoprotein Isolated fromSolanum nigrumL. Kills HT-29 Cells Through Apoptosis
- 1 June 2005
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Medicinal Food
- Vol. 8 (2), 215-226
- https://doi.org/10.1089/jmf.2005.8.215
Abstract
Solanum nigrum L. (SNL) has been used in folk medicine for its anti-inflammatory activity. We previously isolated glycoprotein from SNL and observed that it decreased viable HT-29 cell numbers at a low concentration (60 µg/mL). This study investigated the apoptotic signal pathway triggered by glycoprotein isolated from SNL in HT-29 cells. Treatment of HT-29 cells with SNL glycoprotein (60 µg/mL) for 4 hours resulted in a cytotoxic effect of more than 60%, compared with the control. To explain the apoptotic effects of SNL glycoprotein, we investigated its effects on 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated protein kinase C (PKC) α activity and DNA-binding activity of nuclear factor (NF) κB in HT-29 cells, using western blot analysis and electrophoretic mobility shift assays. Results from these experiments showed that SNL glycoprotein has remarkable inhibitory effects on the activities of TPA (100 nM)-stimulated PKCα and NF-κB in HT-29 cells. They also substantiated that PKCα is a part of the TPA-activated upstream signal pathway of NF-κB, since NF-κB activity was inhibited by staurosporine (a PKC inhibitor) and pyrrolidine dithiocarbamate (an NF-κB inhibitor) in a western blot analysis. Furthermore, to verify the triggering of apoptosis by the SNL glycoprotein, we performed DNA fragmentation, nuclear staining, and protein expression assays of apoptotic-related proteins. The amount of DNA fragmentation and apoptotic cell numbers increased in a dose-dependent manner after treatment with SNL glycoprotein. Apoptosis-related protein assays demonstrated that SNL glycoprotein-induced apoptosis is associated with the regulation of bcl-2 and Bax expression. Taken together, the results of this study showed that the activation of PKCα, NF-κB, and Bax expression by SNL glycoprotein is possibly involved in the apoptotic process. Consequently, these results indicate that SNL glycoprotein causes HT-29 cell death through apoptosis by its ability to modulate anti-apoptotic signals. We suggest that SNL glycoprotein is a natural anti-cancer agent due to its potential to induce apoptosis in HT-29 cells.Keywords
This publication has 50 references indexed in Scilit:
- Antiestrogenic and DNA Damaging Effects Induced by Tamoxifen and Toremifene MetabolitesChemical Research in Toxicology, 2003
- Antioxidative Effects of Glycoprotein Isolated from Solanum nigrum Linne on Oxygen Radicals and its Cytotoxic Effects on the MCF-7 CellJournal of Food Science, 2003
- ANTITUMORIGENIC AND CYTOTOXIC PROPERTIES OF AN ETHANOL EXTRACT DERIVED FROMRhus VernicifluaSTOKES (RVS)Journal of Toxicology and Environmental Health, Part A, 2001
- Colorectal cancer chemoprevention: biochemical targets and clinical development of promising agentsEuropean Journal of Cancer, 2001
- How NF-κB is activated: the role of the IκB kinase (IKK) complexOncogene, 1999
- Control of apoptosis by Rel/NF-κB transcription factorsOncogene, 1999
- Activators and target genes of Rel/NF-κB transcription factorsOncogene, 1999
- Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cellsBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1996
- Regulation of gene expression by tumor promotersPharmacology & Therapeutics, 1990
- Potent selective inhibitors of protein kinase CFEBS Letters, 1989