الفهرس | Only 14 pages are availabe for public view |
Abstract Cancer comprises at least 100 different diseases, and each is classified by the type of cell that is initially affected. Breast cancer is a type of cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas, while those originating from lobules are known as lobular carcinomas. Breast cancer occurs in humans and other mammals remainder of the breast is made up of fatty, connective, and lymphatic tissue. Most masses are benign; that is, they are not cancerous, do not grow uncontrollably or spread, and are not lifethreatening. The aim of this study is to evaluate the antitumor activity of nine Schiff base complexes in Nano size particles against breast cancer cell lines MCF-7 (invitro study), and the toxicity of these complexes against normal animals by measuring : Methodology: Transmission electron microscope: TEM samples for the colloidal suspensions of all nine tested metal complexes in dis.water were prepared by dropping the colloids onto carbon-coated TEM grids (Carbon coated Cu grids, Ted Pella, Redding, CA, USA) and allowing the liquid carrier to evaporate in air then assaying by a JEOL 1230 transmission electron microscope (120 kV). Invitro study: The chemotherapeutic effect was measured in vitro for the synthesized complexes using the Sulfo-Rhodamine-B-stain (SRB). The chemotherapeutic activity of the tested complex NPs determined by comparing it with the standard drug (Vinblastine Sulfate). Animals: 90 healthy male albino rats 8 weeks old (180 - 200 g) were purchased from National Cancer Institute, Cairo, Egypt. Rats were housed in cages at regulated temperature (22- 25 °C). They were kept under good ventilation under a photoperiod of 12-h light/12-h darkness schedule with lights-on from 06:00 to 18:00. They all received a standard laboratory diet (60% ground corn meal, 10% bran, 15% ground beans, 10% corn oil, 3% casein, 1% mineral mixture and 1% vitamins mixture), purchased from Meladco Feed Company (Obor City, Cairo, Egypt) and supplied with drinking water throughout the experimental period. Acute toxicity study: Determination of lethal dose 50 (LD50) using experimental animals. In screening drugs, determination of LD50 is usually an initial step in the assessment and evaluation of the toxic characteristics of a substance. The LD50 of the studied compounds was determined as described by Akhila et al. Invivo study: Animals were allowed 10 days for adaptation. They were then randomly distributed into 5 equal groups, 10 rats each. The animal groups were recognized as follows: 1- group 1 (Control): Normal healthy control animals. 2- group 2: Each animal was injected intra peritoneal with 1x10-5 mmole/L of complex (1) for 6 weeks. 3- group 3: Each animal was injected intra peritoneal with 1x10-5 mmole/L of complex (2) for 6 weeks. 4- group 4: Each animal was injected intra peritoneal with 1x10-5 mmole/L of complex (8) for 6 weeks. 5- group 5: Each animal was injected intra peritoneal with 1x10-5 mmole/L of complex (9) for 6 weeks. Blood collection and tissue preparation: At the end of the experimental period (6 weeks), blood samples were collected from overnight rats, centrifuged at 3000 rpm for 10 min and the separated sera were frozen at -20 °C for future biochemical analysis. Biochemical analysis: Liver enzymes activities, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated using kinetic kits purchased by Human Diagnostic Kits, Germany. The liver function, albumin concentration and kidney functions, blood urea and serum creatinine were measured using Diamond Diagnostic kits, Egypt. All biochemical analysis were determined using a Biosystems BTS-310 Spectrophotometer. Results: The obtained data indicate the surviving fraction ratio against MCF-7 tumor cell line increasing with the decrease of the concentration in the range of the tested concentrations. This can be explained as some metal ions bind to DNA. It seems that, changing the anion and the nature of the metal ion has effect on the biological behavior, due to alter binding ability of DNA binding, so testing of different complexes is very interesting from this point of view. Chemotherapeutic activity of the complexes may be attributed to the central metal atom which was explained by Tweedy’s chelation theory. Also, the positive charge of the metal increases the acidity of coordinated ligand that bears protons, leading to stronger hydrogen bonds which enhance the biological activity. Moreover, metal has been suggested to facilitate oxidated tissue injury through a freeradical mediated pathway analogous to the Fenton reaction. from all of the above, the tested complexes NPs have a great efficacy against breast cancer cell lines (MCF-7). |