OBJECTIVE: In the current scenario, the development of safe and effective drug delivery systems is the utmost concern of formulation development scientists as well as clinicians.
METHODS: Google, Web of Science, and PubMed portals have been searched for potentially relevant literature to get the latest developments and updated information related to different aspects of green synthesized AgNPs along with their biomedical applications, especially in the treatment of different types of cancers.
RESULTS: The present review highlights the latest published research regarding the different green approaches for the synthesis of AgNPs, their characterization techniques as well as various biomedical applications, particularly in cancer treatment. In this context, environment-friendly AgNPs are proving themselves as better candidates in terms of size, drug loading and release efficiency, targeting efficiency, minimal drug-associated side effects, pharmacokinetic profiling, and biocompatibility issues.
CONCLUSION: With continuous efforts by multidisciplinary team approaches, nanotechnology-based AgNPs will shed new light on diagnostics and therapeutics in various disease treatments. However, the toxicity issues of AgNPs need greater attention as unanticipated toxic effects must be ruled out for their diversified applications.
OBJECTIVE: The main objective of this study is to determine the potential anti-proliferative effect of KGM on cancer and normal human liver cell lines, HepG2 and WRL68, respectively.
METHOD: HepG2 and WRL68 cells were treated with KGM, D-mannose, KGM-D-mannose and 5-fluorouracil. The morphological changes in those treated cells were observed. Cytotoxic effect of the treatments on cell viability and proliferation, and apoptosis genes expression were assessed by cytotoxicity assay, flow cytometry and RT-PCR analyses.
RESULTS: The results show that KGM treatment resulted in reduced viability of HepG2 cells significantly, in line with the apoptosis-like morphological changes. Up-regulation of BAX and down-regulation of BCL2 genes as reflected by high Bax to Bcl 2 ratio suggests that the inhibitory effect of KGM on HepG2 cells most likely via Bcl2/Bax protein pathway. Despite the effectiveness of standard drug 5-FU in suppressing the viability and proliferation of HepG2 cells, it however, exhibited no selective inhibition of cancer cells as compared to KGM.
CONCLUSION: Current findings suggested that KGM is a potential anti-cancer compound/drug entity, which could be an alternative preventive agent against liver cancer.
OBJECTIVE: Camptothecin (CPT) is one of the most promising anticancer drugs but it produces various side effects because of its non-selectivity towards cancer cells. To overcome these adverse effects, we synthesized biotin conjugate of camptothecin, which was linked via a self-immolative disulfide linker (CPT-SS-Biotin).
METHODS: Biotin conjugated camptothecin linked through a disulfide bond was synthesized following schemes, and the structural characterization was carried out. The stability and drug release studies were performed in the presence of glutathione (GSH) while in vitro studies were performed on 4T1 tumor cell lines. In vivo pharmacological investigation was done using an antitumor Wistar rat model.
RESULTS: The stability and drug release studies were performed in the presence of glutathione (GSH), and CPT-SSBiotin was found to be physiologically stable moiety and can only be cleaved in the presence of GSH to release free CPT. The CPT-SS-Biotin showed higher toxicity in the biotin-overexpressing 4T1 tumor cell line with a lower IC50 value (8.44 μM) compared to camptothecin alone (IC50 > 30 μM). CPT-SS-Biotin also showed 10.6% higher cellular uptake by cells in comparison to free camptothecin. The CPT-SS-Biotin was delivered to cells by binding to the biotin receptors on the cell surface, followed by energy-dependent endocytosis and internalization to cause cellular toxicity.
CONCLUSION: In-vivo tumor suppression studies and in vitro cell line studies along with serological parameters and histopathological studies showed that conjugate produced a high therapeutic effect and remarkably reduced toxic effects in comparison to free CPT. The results suggested that biotinylation of camptothecin via disulfide linker can be a safe and efficacious method in cancer therapeutics.
BACKGROUND: Breast cancer is a heterogeneous disease involving complex mechanisms. TRAIL is a potential anticancer candidate for targeted treatment due to its selective killing effects on neoplastic cells. Nonetheless, resistance occurs in many cancers either intrinsically or after multiple treatments.
OBJECTIVE: Therefore, this research investigated whether the combination of Trichostatin A (TSA) and Zebularine (Zeb) (TZ) followed by TRAIL (TZT) could sensitize the human breast adenocarcinoma cells towards apoptosis.
METHODS: The breast adenocarcinoma cells, MDA-MB-231, MCF-7 and E-MDA-MB-231 (E-cadherin re-expressed MDA-MB-231) were treated with TSA, Zeb, TZ, TRAIL and TZT. The cells were subjected to hematoxylin and eosin (H & E) staining and FITC-Annexin V/Propidium Iodide apoptosis detection prior to proteome profiling.
RESULTS: Based on morphological observation, apoptosis was induced in all cells treated with all treatment regimens though it was more evident for the TZT-treated cells. In the apoptosis detection analysis, TZ increased early apoptosis significantly in MDA-MB-231 and MCF-7 while TRAIL induced late apoptosis significantly in E-MDA-MB-231. Based on the proteome profiling on MDA-MB-231, TRAIL R2 and Fas expression was increased. For E-MDA-MB- 231, down-regulation of catalase, paraoxonase-2 (PON2), clusterin, an inhibitor of apoptosis proteins (IAPs) and cell stress proteins validated the notion that E-cadherin re-expression enhances TZT anti-cancer efficacy. Similar trend was observed in MCF-7 whereby TZT treatment down-regulated the anti-apoptotic catalase and PON2, increased the proapoptotic, B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax), second mitochondria-derived activator of caspase (SMAC) and HtrA serine peptidase 2 (HTRA2) as well as TRAIL receptors (TRAIL R1 and TRAIL R2).
CONCLUSION: TZ treatment serves as an efficient treatment regimen for MDA-MB-231 and MCF-7, while TRAIL serves as a better treatment option for E-MDA-MB-231. Therefore, future studies on E-cadherin's positive regulatory role in TRAIL-induced apoptosis are warranted.
METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes.
RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 μM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 μM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects.
CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.
METHODS: The two ONBDC derivatives - ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) - were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay.
RESULTS: Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 μM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 μM).
CONCLUSION: Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.