ABSTRACT
This study aims to determine the antitumor potential of cashew gum in vitro and in vivo. The cashew gum (CG) structure is similar to already showed in literature. The cytotoxicity effect of CG was performed by MTT assay, and B16-F10 melanoma model was used to evaluate antitumor effect. The tumor inhibition was calculated based on tumor weight. Hematological, histopathological, FTIR, oxidative stress and Western Blot analysis were performed to elucidate the mechanism of inhibition and toxic effects. As results, CG did not demonstrate cytotoxicity in vitro, however showed a significant tumor inhibition in vivo, with about 36.9 to 43% of reduction in tumor mass, with no toxicity to organs. Animals treated with CG did not show toxicity in normal tissues, FTIR spectrum and oxidative stress analysis of the tumor tissue indicated that CG cause tumor inhibition with the presence of apoptosis morphotype cells, without alterations in the levels of antioxidants components. In addition, it was observed that CG reduced the expression of γH2AX without changing the expression of caspase-3. With this, we can suggest that this polymer can assist in the anticancer activity and/or decrease the side effects of standard drugs used in treatment of cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Plant Extracts/pharmacology , Plant Gums/pharmacology , Anacardium/chemistry , Animals , Apoptosis/drug effects , Cell Line, Tumor , Female , Humans , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effectsABSTRACT
The use of natural products in therapeutics has been growing over the years. Lignans are compounds with large pharmaceutical use, which has aroused interest in the search for new drugs to treat diseases. The present study evaluated the cytotoxicity of (-)-trachelogenin, a dibenzylbutyrolactone type lignan isolated from Combretum fruticosum, against several tumor and non-tumor cell lines using the MTT assay and its possible mechanism of action. (-)-Trachelogenin showed IC50 values ranging of 0.8-32.4µM in SF-295 and HL-60 cell lines, respectively and IC50 values >64µM in non-tumor cell lines. (-)-trachelogenin persistently induced autophagic cell death, with cytoplasmic vacuolization and formation of autophagosomes mediated by increasing LC3 activation and altering the expression levels of Beclin-1.
Subject(s)
4-Butyrolactone/analogs & derivatives , Antineoplastic Agents, Phytogenic/pharmacology , Autophagy/drug effects , Colonic Neoplasms/drug therapy , Combretum/chemistry , Drug Discovery , Plant Stems/chemistry , 4-Butyrolactone/adverse effects , 4-Butyrolactone/chemistry , 4-Butyrolactone/isolation & purification , 4-Butyrolactone/pharmacology , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Autophagosomes/drug effects , Autophagosomes/pathology , Beclin-1/agonists , Beclin-1/metabolism , Brazil , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Colonic Neoplasms/pathology , Combretum/growth & development , Ethnopharmacology , HCT116 Cells , Humans , Inhibitory Concentration 50 , Medicine, Traditional , Microtubule-Associated Proteins/agonists , Microtubule-Associated Proteins/metabolism , Molecular Structure , Neoplasm Proteins/agonists , Neoplasm Proteins/metabolism , Plant Stems/growth & development , Vacuoles/drug effects , Vacuoles/pathologyABSTRACT
In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO(2)) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF(4)) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO(2). QPhNO(2) caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO(2) treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry.
