ABSTRACT
The partial efficacy and high toxicity of the current anticancer chemotherapeutics as well as the development of multiple drug resistance are the major problems in cancer therapy. Therefore, there is an emergency need for the development of novel well-tolerated anticancer agents with different mode of action that could be successfully used in combination with other drugs as an adjuvant therapy. The inhibition of intracellular signaling pathways associated with cancer growth and invasiveness is a main therapeutic approach in cancer treatment. It is well known that lipid metabolism is involved in the regulation of key cellular processes such as proliferation, differentiation and apoptosis. Statins and alkylphospholipids are both relatively new synthetic agents with considerable anticancer properties that disturb lipid metabolism and subsequently modulate proliferation and cell survival signaling pathways, leading to apoptosis. Numerous in vitro and in vivo studies have shown promising results for the use of statins and alkylphospholipids as potential therapeutic agents in the treatment of various human malignancies. However, more investigations and clinical trials are needed to assess their optimal safe dose and maximal efficacy and better understand the molecular mechanisms underlying the antitumor effects of these drugs.
Subject(s)
Antineoplastic Agents/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lipid Metabolism/drug effects , Neoplasms/drug therapy , Phospholipids/pharmacology , Animals , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Molecular Structure , Neoplasms/pathology , Phospholipids/chemistrySubject(s)
Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Caffeic Acids/chemistry , Hydroxybutyrates/chemistry , Polyelectrolytes/chemistry , Polyesters/chemistry , Alginates/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Caffeic Acids/pharmacology , Cell Survival/drug effects , Cells, Cultured , Chitosan/chemistry , Escherichia coli/drug effects , Glucuronic Acid/chemistry , HeLa Cells , Hexuronic Acids/chemistry , Humans , Lymphocytes/cytology , Lymphocytes/drug effects , Macrophages/cytology , Macrophages/drug effects , Male , Mice , Microbial Sensitivity Tests , Microscopy, Fluorescence , Spleen/cytology , Staphylococcus aureus/drug effectsABSTRACT
Nanofibrous materials containing the antitumor drug doxorubicin hydrochloride (DOX) were easily prepared using a one-step method by electrospinning of DOX/poly(L-lactide-co-D,L-lactide) (coPLA) and DOX/quaternized chitosan (QCh)/coPLA solutions. The pristine and DOX-containing mats were characterized by ATR-FTIR and X-ray photoelectron spectroscopy (XPS). The release rate of DOX from the prepared fibers increased with the increase in DOX content. The DOX release process was diffusion-controlled. MTT cell viability studies revealed that incorporation of DOX and QCh in the nanofibrous mats led to a significant reduction in the HeLa cells viability. It was found, that the antitumor efficacy of the DOX-containing mats at 6 h was higher than that of the free DOX. SEM, TEM, and fluorescence microscopic observations confirmed that the antitumor effect of QCh-based and DOX-containing fibrous mats was mainly due to induction of apoptosis in the HeLa cells.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Chitosan/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Nanofibers/chemistry , Polyesters/chemistry , Antibiotics, Antineoplastic/administration & dosage , Cell Survival/drug effects , Doxorubicin/administration & dosage , Electrochemical Techniques , HeLa Cells , Humans , Microscopy, Electron, Scanning , Molecular Structure , Photoelectron Spectroscopy , Spectroscopy, Fourier Transform Infrared , Surface PropertiesABSTRACT
The antitumor effect of peroral treatment with coumarin and its main metabolite in humans 7-hydroxycoumarin (7-OHC) against Sarcoma 180 in mice was studied. Both agents inhibited tumor growth and increased survival time of tumor-bearing animals. The antitumor effect was better when coumarins were administered prior to tumor inoculation suggesting that the immunomodulatory potential of coumarins might exceed their well-known direct cytostatic activity. The additive effect of coumarins in combination with a suboptimal LPS dose in tumor growth inhibition was demonstrated. Coumarin treatment enhanced the macrophage migration activity in the presence and absence of LPS and increased nitric oxide release. In vitro, coumarins induced IL-12 in murine macrophages and additively increased the LPS-induced IL-12 release. These data indicate that the immunomodulatory activity of coumarins contributes to their direct cytostatic effect and demonstrate their potential to combine as immunostimulators with other antitumor agents.
