Diallyl disulfide induces apoptosis in human colon cancer cell line (COLO 205) through the induction of reactive oxygen species, endoplasmic reticulum stress, caspases casade and mitochondrial-dependent pathways.

In this study, we investigated the effects of DADS on human colon cancer cell line COLO 205 on cell cycle arrest and apoptosis in vitro. After 24 h treatment of COLO 205 cells with DADS, the dose- and time-dependent decreases of viable cells were observed and the IC50 was 22.47 microM. The decreased percentages of viable cells are associated with the production of ROS. Treatment of COLO 205 cells with DADS resulted in G2/M phase arrest and apoptosis occurrence through the mitochondrial-pathway (Bcl-2, Bcl-xL down-regulation and Bak, Bax up-regulation). DADS increased cyclin B, cdc25c-ser-216-9 and Wee1 but did not affect CDK1 protein and gene expression within 24 h of treatment. DADS-induced apoptosis was examined and confirmed by DAPI staining and DNA fragmentation assay. DADS promoted caspase-3, -8 and -9 activity and induced apoptosis were accompanied by increasing the levels of Fas, phospho-Ask1 and -JNK, p53 and decreasing the mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-9 and -3. The COLO 205 cells were pre-treated with JNK inhibitor before leading to decrease the percentage of apoptosis which was induced by DADS. Inhibition of caspase-3 activation blocked DADS-induced apoptosis on COLO 205 cells.

Crude extracts of Solanum lyratum induced cytotoxicity and apoptosis in a human colon adenocarcinoma cell line (colo 205).

The effects of the crude extract of Solanum lyratum (SLE) on human colon cancer colo 205 cells were investigated. The cell viability, morphological changes of the cells, cell cycle arrest, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (deltapsi(m)) and cell cycle- and apoptosis-associated protein levels and gene expressions were examined in colo 205 cells after exposure to various concentrations of SLE for different time periods. The results indicated that SLE decreased the percentage of viable colo 205 cells accompanied by morphological changes. The most effective concentration of SLE was 300 pg/ml (SLE 300) and this concentration was used for further investigations. SLE induced S-phase arrest and apoptosis (sub-G1) in the colo 205 cells and those effects were dose- and time-dependent. DAPI staining and DNA gel electrophoresis confirmed that SLE induced apoptosis in colo 205 cells. Flow cytometric analysis also showed that SLE 300 promoted ROS production and decreased the deltapsi(m). Western blotting analysis indicated that SLE 300 increased Bax levels and decreased Bcl-2 levels, which caused the loss of deltapsi(m) followed by cytochrome c release and caspase-9 and -3 activation, finally leading to apoptosis. SLE 300 also promoted p53 and p27, but decreased the levels of cyclin B1 thus causing S-phase arrest. The gene expression associated with those proteins was also confirmed by PCR methods. The findings show that SLE might be used as a colon cancer therapeutic agent in the future.

Diallyl disulfide induced signal transducer and activator of transcription 1 expression in human colon cancer colo 205 cells using differential display RT-PCR.

Diallyl disulfide is one of the components of garlic and has been demonstrated to induce apoptosis in many cancer cell lines, though it is not reported to be associated with signal transducer and activator of transcription 1 (STAT1) expression. Moreover the role of STAT1 does not directly affect apoptosis in cancer cells after exposure to chemotherapy agents, though some reports showed that STAT1 is associated with apoptosis. In this study, differential display RT-PCR was used to examine the effects of diallyl disulfide (DADS) on human colon cancer cells (colo 205). The results demonstrated that DADS induced the expression of STAT1 which was also confirmed using Western blotting. STAT1 decoy oligonucleotides were also used to block STAT1 mRNA and led to a decrease in the levels of STAT1 and to subsequence decrease in the percentage of apoptosis induced by DADS in examined colo 205 cells.

Synthesis and cytotoxic activity of certain 2,3,4,9-tetrahydrofuro [2,3-b] quinolin-3,4-dione and ethyl 2-(substituted aniline) -4-oxo-4,5-dihydrofuran-3-carboxylate derivatives in murine leukemia WEHI-3 cells.

A series of 2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione and ethyl 2-(substituted aniline) -4-oxo-4,5-dihydrofuran-3-carboxylate were synthesized and evaluated for cytotoxicity on murine leukemia WEHI-3 cells. The cytotoxic effects of most compounds tested were dose-dependent and the structure-activity relationships indicated that N-substituted benzyl derivatives displayed a stronger inhibitory activity against murine leukemia WEHI-3 cells compared to non-N-substituted benzyl substituted derivatives.

(-)-Menthol inhibits WEHI-3 leukemia cells in vitro and in vivo.

(-)-Menthol ([1-alpha]-5-methyl-2-[1-methylethyl]-cyclohexanol), is a widely used flavoring ingredient in mouthwash, foods, toothpaste and cigarettes. The studies reported here revealed that (-)-menthol induced cytotoxicity against murine leukemia WEHI-3 cells in vitro in a dose-dependent manner. The effects of (-)-menthol on WEHI-3 cells in vivo (BALBIc mice) were also examined, and it was observed that the Mac-3 and CD11b markers were decreased, indicating inhibition of differentiation of the precursor of macrophage and granulocyte. The weights of liver and spleen samples from mice treated with (-)-menthol were found to be decreased compared to untreated animals.

ROS mediates baicalin-induced apoptosis in human promyelocytic leukemia HL-60 cells through the expression of the Gadd153 and mitochondrial-dependent pathway.

BACKGROUND: Chemotherapy agents, particularly those that can induce apoptosis, are the major intervening strategy in the treatment of leukemia. In this study, we investigated the effects of baicalin (a compound obtained from Scutellaria baicalensis Georgi and S. rivularis Benth Labiateae) on the viability, induction of apoptosis and associated mechanism in human leukemia HL-60 cells. MATERIALS AND METHODS: The cell viability and apoptosis was examined by flow cytometric analysis. The results showed that baicalin induced cytotoxicity in a dose- and time-dependent manner through the activation of caspase-3, as shown by treatment of HL-60 cells with an inhibitor of caspase-3 (z-VAD-fmk). Baicalin increased the levels of ROS, Ca2+ and decreased mitochondrial membrane potential in HL-60 cells. Western blot demonstrated that baicalin promoted the levels of Gadd153, Bax, cytochrome c and caspase-3 and -12, but decreased the levels of Grp78 and Bcl-2 in HL-60 cells. CONCLUSION: Baicalin was found to induce apoptosis in HL-60 cells through multiple pathways.