Showing papers by "Yuan Soon Ho published in 2007"

NF‐κB pathway is involved in griseofulvin‐induced G2/M arrest and apoptosis in HL‐60 cells

Abstract: Griseofulvin (GF), an oral antifungal agent, has been shown to exert antitumorigenesis effect through G2/Mcellcyclearrestincoloncancercells.Buttheunderlyingmechanismsremainedobscure.Thepurposeofthisstudyis to test the cytotoxic effect of GF on HL-60 and HT-29 cells and elucidate its underlying molecular pathways. Dose- dependentandtime-coursestudiesbyflowcytometrydemonstratedthat30to60mMGFsignificantlyinducedG2/Marrest and to a less extend, apoptosis, in HL-60 cells. In contrast, only G2/M arrest was observed in HT-29 cells under similar condition. Pretreatment of 30 mM TPCK, a serine protease inhibitor, completely reversed GF-induced G2/M cell cycle arrest and apoptosis in HL-60 cells but not in HT-29 cells. The GF-induced G2/M arrest in HL-60 cells is reversible. Using EMSA and super-shift analysis, we demonstrated that GF stimulated NF-kB binding activity in HL-60 cells, which was completelyinhibitedbypretreatmentofTPCK.TreatmentofHL-60with30mMGFactivatedJNKbutnotERKorp38MAPK and subsequently resulted in phosporylation of Bcl-2. Pretreatment of TPCK to HL-60 cells blocked the GF-induced Bcl-2 phosphorylation but not JNK activation. Time course study demonstrated that activation of cdc-2 kinase activity by GF correlated with Bcl-2 phosphorylation. Taken together, our results suggest that activation of NF-kB pathway with cdc-2 activation andphosphorylation of Bcl-2 mightbeinvolvedin G2/M cellcyclearrest inHL-60 cells. J. Cell. Biochem. 101:

Antitumor Activity of Combination Treatment of Lentinus edodes Mycelium Extracts with 5-Fluorouracil against Human Colon Cancer Cells Xenografted in Nude Mice

Abstract: AIM: 5-Fluorouracil (5-FU) is one of the widely used chemotherapeutic drugs targeting various cancers, but its chemoresistance remains as a major obstacle in clinical settings. In this study, we evaluated the in vivo efficacy of Lentinus edodes mycelium extracts (designated as LEM), an edible mushroom extracts, as a 5-FU adjuvant agent. Furthermore, we intended to study the underlying mechanisms to account for the role of LEM. METHODS: Human colon cancer COLO 205 cells were treated with 5-FU, LEM, or combination of 5-FU with LEM. Induction of apoptosis and cell cycle arrest was demonstrated by DNA ladder electrophoresis and flow cytometry, respectively. Additionally, COLO 205 cells were transplanted into athymic nude mice as a tumor model for evaluation of the antitumor effect of combination treatment with LEM plus 5-FU. The mechanisms for altered cell cycle progression were investigated by immunoblotting analyses of the G 0 /G 1 -phase regulatory proteins. RESULTS: COLO 205 cells were markedly sensitized to apoptosis and G 0 /G 1 -phase arrest by combination treatment of 5-FU with LEM when compared with 5-FU alone. Our results furthermore indicated that LEM markedly enhanced the 5-FU-mediated upregulation of the p53, p21/Cip1 and p27/Kip1 proteins in COLO 205 cells-xenografted tumor tissues. In contrast, although the expression levels of cyclins B and D3 proteins were down regulated in the 5-FU-treated tumor tissues, no significant potentiation effect was observed in the tumors with 5-FU and LEM combination treatment. CONCLUSION: Our results suggest that combination of 5-FU with LEM may represent a novel chemotherapeutic strategy in colon cancers and that p53, p21/Cip1 and p27/Kip1 may play some important roles for the involvement in antitumor activity.