Targeting the Akt signaling pathway: Exploiting curcumin's anticancer potential.

Cancer is recognized as one of the leading causes of death worldwide. In recent years, advancements in early detection and expanding treatment options have contributed to a decrease in mortality rates. However, the emergence of drug-resistant cancers necessitates the exploration of innovative and more effective drugs. The Akt kinases play a central role in various signaling pathways that regulate crucial cellular processes, including cell growth, proliferation, survival, angiogenesis, and glucose metabolism. Due to frequent disruptions of the Akt signaling pathway in numerous human cancers and its broad biological implications, targeting this pathway has become a key focus in combating tumor aggressiveness and a promising avenue for therapeutic intervention. Curcumin, a compound found in turmeric, has been extensively studied for its potential as an anti-cancer agent. It demonstrates inhibitory effects on cancer initiation, progression, and metastasis by influencing various processes involved in tumor growth and development. These effects are achieved through negative regulation of transcription factors, growth factors, cytokines, protein kinases, and other oncogenic molecules. This review aims to explore curcumin's anticancer activity against different types of cancer mediated via the PI3K/Akt signaling pathway, as well as its practical applications in treatment.

Effect of Nigella sativa Intake on Oxidative Stress and Inflammation in Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several studies have shown that the intake of N. sativa has a beneficial effect on metabolic syndrome and related disorders. In this meta-analysis, our primary objective was to assess the impact of Nigella sativa consumption on inflammation and oxidative stress biomarkers among individuals diagnosed with metabolic syndrome and its associated conditions. METHODS: Our search was conducted on prominent online databases such as Web of Science, Scopus, PubMed, and EMBASE, utilizing relevant keywords until August 2023. RESULTS: This meta-analysis was performed on 16 RCTs comprising 1033 participants. Our results showed that intake of nigella sativa significantly decreased CRP [SMD: -0.60; (95% CI: from -0.96 to -0.23); P = 0.00], TNF-α [SMD: -0.53; (95% CI: from -0.74 to -0.53); P = 0.00]; IL-6 [SMD: -0.54 ; (95% CI: from -1.01 to -0.07); P = 0.02], and MDA: [SMD: -1.28; (95% CI: from -2.11 to -0.46); P = 0.00] levels. In addition, SOD: [SMD: 1.35; (95% CI, from 0.77 to 1.93); P = 0.00] and TAC [SMD: 2.82; (95% CI, from 0.55 to 5.084); P = 0.01] levels significantly increased in the intervention group compared to the placebo group. CONCLUSION: Our results showed that THE consumption of N. sativa could be associated with improved oxidative stress and inflammation in patients with metabolic syndrome and related disorders.

Association Between Vitamin D Binding Protein Gene Polymorphism (rs7041), Vitamin D Receptor, and 25-Hydroxyvitamin D Serum Levels With Prostate Cancer in Kurdish Population in West of Iran.

Prostate cancer (PCa) pathology has been linked to vitamin D, vitamin D receptors (VDRs), and vitamin D binding proteins (VDBPs). We sought to investigate the association between VDR rs2228570 and rs1544410 as well as VDBP rs7041 polymorphisms and serum 25-hydroxyvitamin D (25(OH)-vitamin D) levels in PCa patients. Blood samples were collected from 111 PCa patients and 150 age-matched healthy volunteers. The VDR rs2228570 T/C, rs1544410 G/A, and VDBP rs7041 T/G genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). 25(OH)-vitamin D and PSA (Total and Free) serum levels were measured. The frequencies of VDBP genotypes T/G vs. T/T (56.5% vs. 44.5%, p = 0.01) according to the dominant model T/G + G/G vs. T/T (84.3% vs. 71.5%, p = 0.01) were significantly higher in PCa patients when compared to control group and considerably increased the risk of disease by 2.29, 1.44, and 2.13 folds respectively. Interestingly, the results demonstrated that PCa patients with the dominant model (T/G + G/G vs. T/T) of VDBP had significantly lower serum levels of vitamin D and higher serum levels of total and free PSA in comparison to the controls. Furthermore, when compared to controls, PCa patients with the dominant model T allele (T/G + G/G vs. TT) of VDBP had significantly higher vitamin D, total PSA, and free PSA concentrations. Serum levels of 25(OH)-vitamin D and rs7041 T/G polymorphism of the VDBP gene could be potential risk factors for PCa.

The role of caveolin-1 and endothelial nitric oxide synthase polymorphisms in susceptibility to prostate cancer.

Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of NO2- and NO3- were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT + TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT + TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P = .004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P = .009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.

Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer.

Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case-control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR-RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.