7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS(+) scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.
- MeSH
- Antioxidants chemical synthesis chemistry pharmacology MeSH
- Benzothiazoles chemical synthesis chemistry pharmacology MeSH
- Madin Darby Canine Kidney Cells MeSH
- Flavonoids chemical synthesis chemistry pharmacology MeSH
- HeLa Cells MeSH
- Inhibitory Concentration 50 MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Drug Evaluation, Preclinical MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Dogs MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Dogs MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Mechanisms and pathways responsible for cytotoxicity of sulforaphane (SF) in colon cancer cells with deleted p53 were investigated during 48 h of exposure. SF showed dose-dependent cytotoxicity and proapoptotic activity in the present model. In addition, in HCT-116 p53KO cells SF induced DNA damage with the subsequent cellular response and signaling not including p53 and caspase-2 pathways. Conversely, in SF-treated cells JNK was activated which led to an early lysosomal membrane permeabilization, release of cathepsin B and D and activation of Bid by specific cleavage. Concomitantly, the expression of Bax increased in the presence of JNK-mediated Bcl-2 inhibition which was followed by mitochondrial release of cytochrome c and activation of apoptosis. These results suggest that SF may be useful as a chemopreventive agent in colon cancer with inactivated or lost p53.
- MeSH
- Anticarcinogenic Agents toxicity MeSH
- Time Factors MeSH
- Gene Deletion MeSH
- Stress, Physiological drug effects MeSH
- HCT116 Cells MeSH
- Humans MeSH
- Lysosomes drug effects metabolism MeSH
- MAP Kinase Kinase 4 genetics metabolism MeSH
- Mitochondria drug effects metabolism MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- Colonic Neoplasms genetics metabolism prevention & control MeSH
- DNA Damage drug effects MeSH
- Cell Proliferation drug effects MeSH
- bcl-2-Associated X Protein genetics metabolism MeSH
- Heat-Shock Proteins genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Thiocyanates toxicity MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Despite the reported cytotoxicity and apoptosis-inducing properties of sulforaphane (SF) in colon cancer cells, the details concerning individual mechanisms and signaling cascades underlying SF-mediated apoptosis remain unclear. To understand different aspects of SF-induced proapoptic signaling in advanced colon carcinoma, we investigated its mechanisms in metastatic SW620 cell line. Our results indicate that in SW620 cells SF acts to induce multivariate cascades including DNA-damage response pathway whose proapoptotic signaling is nevertheless reduced owing to the mutant status of p53 and caspase-2-JNK pathway which seems to complement and enhance p53-dependent signaling, however only in wild-type p53. Furthermore, both pathways require the active role of mitochondria and do not depend on generation of ROS, making SF an attractive chemopreventive agent whose antitumor properties should be further investigated in colon cancer.
- MeSH
- Anticarcinogenic Agents pharmacology MeSH
- Apoptosis drug effects MeSH
- Cytochromes c metabolism MeSH
- JNK Mitogen-Activated Protein Kinases metabolism MeSH
- Caspase 2 metabolism MeSH
- Humans MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- Colonic Neoplasms drug therapy metabolism pathology MeSH
- Oxidative Stress drug effects MeSH
- DNA Damage MeSH
- Drug Screening Assays, Antitumor MeSH
- Thiocyanates pharmacology MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
... Evaluation of the effect of individual additives 58 -- Method: Improving the efficiency of PCR amplification ... ... Methods for the isolation of RNA suitable for RT-PCR 91 -- XIII -- Method 1: Acid guanidinium thiocyanate-phenol-chloroform ... ... extraction 92 -- Method 2: Microadaption of the guanidinium-thiocyanate/CsCI ultracentrifugation method ...
271 s. : il.
- MeSH
- Clinical Laboratory Techniques MeSH
- Molecular Biology MeSH
- Polymerase Chain Reaction MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Biologické vědy
- NML Fields
- biologie
- MeSH
- Benzofurans MeSH
- Chlorates MeSH
- Liver physiology MeSH
- Iodine metabolism MeSH
- Rats MeSH
- Thiocyanates MeSH
- Thyroxine metabolism MeSH
- Research MeSH
- Check Tag
- Rats MeSH
- MeSH
- Rats MeSH
- Nitriles analogs & derivatives administration & dosage metabolism MeSH
- Radioisotopes urine MeSH
- Check Tag
- Rats MeSH
- MeSH
- Liver physiology MeSH
- Rats MeSH
- In Vitro Techniques MeSH
- Thyroxine MeSH
- Binding Sites MeSH
- Check Tag
- Rats MeSH
