The health benefits of garlic have been proven by epidemiological and experimental studies. Diallyl disulphide (DADS), the major organosulfur compound found in garlic oil, is known to lower the incidence of breast cancer both in vitro and in vivo. The studies reported here demonstrate that DADS induces apoptosis in the MCF-7 breast-cancer cell line through interfering with cell-cycle growth phases in a way that increases the sub-G(0) population and substantially halts DNA synthesis. DADS also induces phosphatidylserine translocation from the inner to the outer leaflet of the plasma membrane and activates caspase-3. Further studies revealed that DADS modulates the cellular levels of Bax, Bcl-2, Bcl-xL, and Bcl-w in a dose-dependent manner, suggesting the involvement of Bcl-2 family proteins in DADS induced apoptosis. Histone deacetylation inhibitors (HDACi) are known to suppress cancer growth and induce apoptosis in cancer cells. Here it is shown that DADS has HDACi properties in MCF-7 cells as it lowers the removal of an acetyl group from an acetylated substrate and induces histone-4 (H4) hyper-acetylation. The data thus indicate that the HDACi properties of DADS may be responsible for the induction of apoptosis in breast cancer cells.
Our research is an additional genetic study to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying loss of heterozygosity (LOH) and microsatellite instability (MSI) in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. Patients with HNSCC from various parts of the world may have unique genotypes and this is the first genetic study of HNSCC in Sohag 500 KM to the south of Cairo. We performed a prospective study of 41 patients with precancerous and 79 patients with cancerous laryngeal, esophageal, nasopharyngeal, nasal and oral lesions, and 50 controls (The control patients were cases admitted for ear surgery or simple nasal surgery, from whom we took biopsy from mucosal lining of nasopharynx). The present study included 170 individuals who were admitted to the Ear, Nose and Throat department, Sohag University Hospital, Sohag, in Egypt in the period between April 2001 and March 2003. Samples which were taken by punch biopsy were frozen and stored at -80 degrees C and were subjected to histopathological examination. We investigated LOH and MSI by using six microsatellite markers located at chromosomes 3, 5, 9, and 17. The markers used were D3S1286, D9S171, D9S753, D17S654, D17S695, and CFS1-R. LOH was in all premalignant and malignant lesions at 5q33.3-q34 and 13% of Controls. LOH at 17p21 was absent in all premalignant lesions and was found in 53% of malignant lesions and 12.4% of Controls. In premalignant lesions, LOH was at 3pter-3p24.2 (73% of cases), at 9p21 (46%), at 9q21.1-22.3 (37%), and at 17p13 (37%). These percents increased in malignant lesions to 87, 80, 67, and 63%, respectively. They were 14, 19.4, 17, and 19% in controls. Examination of LOH could improve diagnosis, adds additional confidence, in HNSCC by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and LOH at 3p/9p seems to be of particular value for early detection and definition of progression risk. If there are high percent of LOH at these chromosomes, active intervention should be done (chemoprevention and regular follow up head and neck examination for very early detection and management).
The objectives of this study are to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying the chromosomal aberrations in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. From March 2001 to December 2003, prospective study was conducted in 41 patients with precancerous, 79 patients with cancerous laryngeal, oesophageal, nasopharyngeal, nasal, and oral lesions and 50 controls in ENT department, Sohag Faculty of Medicine, Sohag, Egypt. Samples taken by punch biopsy were frozen and stored at -80 degrees C and were subjected to histopathological examination. Metaphase cells were digitally imaged and karyotyped. Karyotypes have been analysed via anatomical image capture and compared with standard human chromosome ideograms. In precancerous lesions, there were 41% 3p loss, 51% 3q gain, 29% 8q gain, and 22% 11q13 gain. In malignant lesions, there were 63% 3p13-p24 loss, 59.5% 5q12-23 loss, 49.5% 8p22-p23 loss, 45.5% 9p21-p24 loss, 40.5% 18q22-q23 loss, 66% 3q gain, 39% 8q gain, and 16% 11q13 gain. In conclusion, early diagnosis of HNSCC can be achieved by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and examination of chromosomal aberrations of 3p, 3q, 8q, and 11q13. If there are high percent of chromosomal aberrations in these chromosomes, active intervention should be done (chemoprevention and regular follow-up of head and neck examination for very early detection and management).
Diet and dietary habits are currently accused of being among cancer causing agents. The present study was carried out in a trial to point at the beneficial anti-cancer properties of one the most Egyptian traditional food components (Garlic). We studied the anti-cancerous properties of Diallyl disulphide (DADS), a major organosulfur compound in garlic oil, on HT29 colon cancer cell line and in vivo of male rabbits (Oryctolagus cuniculus) as an animal model of colon cancer. DADS showed differential effect on the expression of a group of genes, as it down-regulated the expression of oncogenes (e.g., CTNNB1, CCDN1, BIRC5, MYC and AKT), while up-regulated the expression of tumour suppressor gene (TP53) and apoptosis regulator gene (BAX). DADS' apoptotic effect was also seen via inducing the expression of cytochrome c and activation of caspase-3. Moreover, DADS induced chromatin configuration changes through increasing histone acetylation of histone-3 and -4. Examination of 1,2 dimethyl hydrazine (DMH) induced cancer in vivo model (O. cuniculus) showed histological changes characteristic for colon tumorigenesis such as, hyperplastic intraepithelial lesions, neoplastic changes and lymphocytes infiltration, which were strongly attenuated in animals coinjected with both DADS and DMH and were not observed in the animals that received DADS prior to DMH treatment. This study suggested the protective properties of DADS against colon cancer in vitro and in vivo.
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