Antitumor effect of proanthocyanidin induced apoptosis in human colorectal cancer (HT-29) cells and its molecular docking studies.

Proanthocyanidin (PAC) is a promising compound that has displayed its potent antineoplastic properties with a specific intrinsic pathway. This precise us to explore the phyto-preventive effect of PAC against colon cancer (HT-29). The results showed that PAC inhibited the cell growth and GI50 value was found to be 6.25 µM for 24 h exposure, when correlated to the normal cell line does not have toxicity was noticed. The linguistic differences, similarly membrane blebbing, cell shrinkage fragmented nuclear bodies and mitochondrial membrane were observed in AO/EtBr and DAPI staining. The features of regular mechanical apoptotic characterization was analyzed by DNA fragmentation. The cell cycle arrest at G2/M phases was detected using FACS analysis. The early and late apoptotic cells were observed by using Annexin V/PI staining. The ligand-protein interaction and docking studies were performed using Schrodinger's software. The QPLD analysis of docking studies revealed that PAC exhibited better binding affinity of - 5.23, - 5.17 and - 4.43, - 4.47 kcal/mol against BCL-XL, CDK2 and were compared with 5-FU respectively, which significantly reveals the anticancerous activity of Proanthocyanidin compound. Thus, the PAC compound provides future application of therapeutic option in the treatment of colon cancers.

Mitochondrial dysfunction mediated apoptosis of HT-29 cells through CS-PAC-AgNPs and investigation of genotoxic effects in zebra (Danio rerio) fish model for drug delivery.

The present study reports the validation of cancer nanotherapy using proanthocyanidin (PAC). Nowadays, in vitro and in vivo deliveries of nanoparticle (NPs) drugs have been paid more attention, intensively. Moreover, the current chemotherapeutic drugs have few first rate drawbacks including lack of specificity and requirement of excessive drug doses. To overcome this problem of chemotherapy, the attainment of high drug loading in combination with degradable polymer nanoparticles (for instance,chitosan) is a trending research in cancer biology. Hence, in this study, the synthesized PAC-AgNPs were successfully crosslinked with chitosan nanoparticles (CS-PAC-AgNPs), which were found to be spherical or polygonal in shape with a median size of 70.68 nm and 52.16 nm as observed by FTIR, FESEM and TEM analysis; thus, being suitable for drug delivery. CS-PAC-AgNPs were taken up via endocytosis by cancer cells and enabled the release cytochrome-C from mitochondria, followed by dysregulation of anti-apoptotic protein Bcl2 family, inducing the apoptotic mediated activation of caspase 9 and 3. To identify the genotoxicity of the synthesized CS-PAC-AgNPs, the mortality, hatching rate, malformation and abnormalities of embryo/larvae of the vertebrate zebra fish model (Danio rerio) were observed in a dose-time-dependent manner. This improved cancer nanotherapy can thus be utilized as a novel nanocombination for inducing apoptosis in vitro and in vivo.