ABSTRACT
Background: Cancer constitutes a major hurdle worldwide and its treatment mainly relies onchemotherapy.Objectives: The present study was designed to evaluate the cytotoxicity of eleven naturally occurringcompounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normalCRL2120 fibroblasts.Materials and methods: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of thecompounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrialmembrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygenspecies (ROS) was measured by spectrophotometry.Results: Chalcones: 20,40-dihydroxy-60-methoxychalcone (1); 40,60-dihydroxy-20,50-dimethoxychalcone(2); 20,40,60-trihydroxy-50-methoxychalcone (3); 20,60-diacetate-40-methoxychalcone (4), trachylobanediterpenoids: 2,6,19-trachylobanetriol; (ent-2a,6a)-form (10) and 2,18,19-trachylobanetriol; (ent-2a)-form (11) as well as doxorubicin displayed IC50 values below 110 mM in the six tested cancer cell lines. TheIC50 values of the most active compounds were between 6.30 mM and 46.23 mM for compound 1respectively towards breast adenocarcinoma MCF-7 cells and small lung cancer A549 cells and between0.07 mM and 1.01 mM for doxorubicin respectively against SPC212 cells and A549 cells. Compounds 1induced apoptosis in MCF-7 cells mediated by increasing ROS production and MMP loss.Conclusion: Chalcones 1e3 are potential cytotoxic phytochemicals that deserve more investigations todevelop novel anticancer drugs against human carcinoma.© 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
ABSTRACT
The aims of this study are the investigation of the effects of fibronectin and type IV collagen extracellular matrix proteins and the role of caspase-3 and -9 on cis-platin induced U2-OS apoptosis were studied. First the cytotoxic effects of cis-platin on cell system were investigated by colorimetric method and than morphological and ELISA analysis were used for determination of cell apoptosis when induced with cis-platin. In addition, after adhering the cells to fibronection or type IV collagen proteins, the apoptotic rate and the effects of caspase-3 and -9 were also investigated by ELISA in presence of specific inhibitors. U2-OS cells showed 20% cytotoxicity after treatment with 2.4 µM of cis-platin for 48 h. Morphological and the numerical data showed that cis-platin was able to induced apoptosis on cells as a dose-dependent manner. Caspase-3 and -9 inhibitors inhibited cis-platin-induced apoptosis in U2-OS cells, respectively. The binding of cells to 10 µg/mL of fibronectin but not type IV collagen enhanced the apoptosis about 2.5 fold that effects inhibited with caspase-3 inhibitor. The caspase-3 and -9 are involved in the apoptotic signals induced by cis-platin in U2-OS. The binding to fibronectin, but not type IV collagen enhanced the apoptotic response of U2-OS and fibronectin-dependent apoptosis was activated by caspase-3. These finding might be useful for patients to fight against osteosarcoma.