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1.
Environ Toxicol Pharmacol ; 102: 104218, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37451528

ABSTRACT

Cadmium chloride (Cd) and sodium arsenite (As) are two prominent examples of non-biodegradable substances that accumulate in ecosystems, pose a serious risk to human health and are not biodegradable. Although the toxicity caused by individual use of Cd and As is known, the toxicity of combined use (Cd+As) to mammals is poorly understood. The present study aims to investigate the hepatoprotective effect of curcumin (CUR), a naturally occurring bioactive component isolated from the root stem of Curcuma longa Linn., in preventing liver damage caused by a Cd+As mixture. A group of 30 Sprague-Dawley rats were subjected to intraperitoneal administration of Cd+As (0.44 mg/kg+5.55 mg/kg i.p.) and CUR (100 or 200 mg/kg) for a period of 14 days. The experimental results showed that the animals treated with Cd+As exhibited changes in liver biochemical parameters, inflammation and oxidative stress at the end of the experiment. Administration of CUR significantly reduced inflammation, oxidative stress and lipid peroxidation in the Cd+As plus CUR groups compared to the Cd+As group. Furthermore, histological examination of the liver tissue showed that administration of CUR had led to a significant reduction in the liver damage observed in the Cd+As group. The present study provides scientific evidence for the protective effects of CUR against lipid peroxidation, inflammation, oxidative stress and liver damage induced by Cd+As in the liver of rats. The results of our in vivo experiments were confirmed by those of our molecular modelling studies, which showed that CUR can enhance the diminished antioxidant capacity caused by Cd+As.


Subject(s)
Arsenic , Curcumin , Liver Diseases , Humans , Rats , Animals , Cadmium/metabolism , Curcumin/pharmacology , Arsenic/toxicity , Arsenic/metabolism , NF-kappa B/metabolism , Interleukin-1beta/metabolism , Ecosystem , Rats, Sprague-Dawley , Antioxidants/pharmacology , Antioxidants/metabolism , Oxidative Stress , Liver , Liver Diseases/metabolism , Inflammation/metabolism , Mammals
2.
Anticancer Agents Med Chem ; 22(18): 3157-3162, 2022.
Article in English | MEDLINE | ID: mdl-35473537

ABSTRACT

AIM: Cervical cancer is the deadliest gynecological malignancy. This study aims to examine the anticancer effects of L-citrulline on HeLa cell culture. MATERIALS AND METHODS: HeLa cells were cultured in complete Eagle's minimum essential medium. HeLa cells were seeded in 96-well plates and incubated with L-citrulline. After incubation, MTT dye was added and incubated. Annexin- V technique was used to test the apoptosis. The activated caspases of HeLa cells by L-citrulline exposure were measured with the Caspase 3/7 technique. One-way variance analysis was conducted for statistical analysis by using GraphPad Prism 6.0 for Windows. RESULTS: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner in application times of 24 and 48 hours. The IC50 dose of L-citrulline was 0.19 and 0.16 mg/mL at 24 and 48 hours, respectively. When HeLa cells were exposed to an IC50 dose of L-citrulline for 24 hours, the percentages of the dead, early apoptotic, and late apoptotic cells were detected to be 0.75%, 23.05%, and 12.75%, respectively. The differences in the wideness of the scratch area were observed at the initial stage and after 24 hours of applying L-citrulline. CONCLUSION: L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner. Based on Annexin and Caspase findings, it can be concluded that L-citrulline exerted a pro-apoptotic effect on HeLa cells in only a short exposure time. L-citrulline also showed a migration inhibitory effect. The findings of this study indicate L-citrulline to be worthy of investigation for its anticancer activities in vitro and in vivo, and as a candidate for cancer therapy.


Subject(s)
Uterine Cervical Neoplasms , Annexin A5 , Apoptosis , Caspase 3/metabolism , Caspases/metabolism , Cell Proliferation , Citrulline/pharmacology , Citrulline/therapeutic use , Female , HeLa Cells , Humans , Uterine Cervical Neoplasms/drug therapy
3.
Anticancer Agents Med Chem ; 22(16): 2896-2901, 2022 08 04.
Article in English | MEDLINE | ID: mdl-35473538

ABSTRACT

INTRODUCTION: Ovarian cancer is the deadliest gynecological malignancy, usually not detected until the late stages. In vitro cell culture is a method used to study the behavior of cells in a controlled environment. Turmeric has attracted the attention of scientists due to its anticancer potential. METHODS: OVCAR-3 cells were cultured in RPMI medium with 100 units/mL-100 µg/mL of penicillin-streptomycin and 10% foetal bovine serum in a CO2 incubator. Turmeric extract was diluted in DMSO. Different concentrations of turmeric extract were prepared. Annexin-V staining was performed to test the translocation of phosphatidylserine to the outer side of the cell membrane as a clear indicator of apoptosis. RESULTS: Turmeric extract significantly reduced the viability of OVCAR-3 cells both within 24 and 48 hours of exposure. OVCAR-3 cells were treated with IC50 concentration of turmeric extract for 24 hours. 82.60% of cells were viable. The percentages of the dead, early apoptotic, and late apoptotic cells were detected to be 0.80%, 9.70%, and 6.90%, respectively. Untreated OVCAR-3 cells had migration ability. OVCAR-3 cells exposed to an IC50 concentration of turmeric extract for 24 hours did not close the scratch area. CONCLUSION: In this research, anticancer effects of turmeric have been demonstrated by different analysis methods.


Subject(s)
Curcuma , Ovarian Neoplasms , Apoptosis , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cell Proliferation , Female , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology
4.
Anticancer Agents Med Chem ; 22(6): 1119-1123, 2022.
Article in English | MEDLINE | ID: mdl-34139986

ABSTRACT

BACKGROUND: Cancer is a complex disease that derives from the uncontrolled proliferation of cells. Bone cancer is a type of prevalent cancer that occurs both in young and adults. Bone cancer is most common in the long bones of the pelvis, arms and legs. Statistically, more than 200 cases of osteosarcoma have been reported annually in our country. Classical treatment with chemotherapeutics remains ineffective in the cure of this cancer type. Recent studies have shown that ceramide induces apoptosis at its increased levels in the cells. Thus, many studies have been conducted to cause the accumulation of ceramide molecules in the cell by different ways to induce apoptosis. NOE (Noleoylethanolamine) is a specific inhibitor of ceramidase enzymes that hydrolyze intracellular ceramides and prevent apoptosis. OBJECTIVE: This study investigates the cytotoxic and apoptosis-inducing activities of NOE on human osteosarcoma Saos-2 cells. METHODS: Cytotoxic effects were investigated by MTT colorimetric assay. For the detection of morphological and ultrastructural indicators of apoptosis, confocal and TEM techniques were used. RESULTS: Our finding indicated that NOE is effective in the inhibition of the growth of Saos-2 cells. Confocal and TEM findings showed morphological and ultrastructural changes as chromatin condensation, fragmentation of nuclei and mitochondria as well as damaged cytoskeleton and cell shrinkage. CONCLUSION: The results revealed that NOE exerts its cytotoxicity on Saos-2 cells through changing the ultrastructure and morphology of cells with clear apoptotic sparks.


Subject(s)
Antineoplastic Agents , Bone Neoplasms , Osteosarcoma , Antineoplastic Agents/pharmacology , Apoptosis , Bone Neoplasms/drug therapy , Cell Line, Tumor , Ceramides/pharmacology , Ceramides/physiology , Endocannabinoids , Ethanolamines , Humans , Oleic Acids/pharmacology , Osteosarcoma/drug therapy
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