ABSTRACT
Background: Glial tumors are the most common primary malignant central nervous system tumors. They are hard to treat, not only because of the deregulation in multiple pathways but also because they are not contained in a well-defined mass with clear borders. The use of a single therapeutic agent to target gliomas has yielded unsatisfactory results. Objective: A combination of molecules targeting multiple pathways may prove to be a better alternative. Methods: The effect of caffeic acid phenethyl ester and crocin on the proliferation and death of U87-MG cells over a concentration range was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. A colony formation assay was used to measure the effect of caffeic acid phenethyl ester and crocin on contact inhibition and anchorage independence ability of U87-MG cells. Furthermore, apoptosis in U87-MG cells was analyzed by propidium iodide assay. Real-time polymerase chain reaction and Western blotting were performed to determine the expression level of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen. Results: Caffeic acid phenethyl ester and crocin when used in combination present an anticancer potential for glioma. These molecules, in combination, inhibit proliferation and induce apoptosis in U87-MG glioma cells. Our results provide evidence that combination treatment realigns the expression paradigm of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen in cotreated U87-MG cells. Conclusions: The combination of caffeic acid phenethyl ester and crocin led to inhibition in glioma cell proliferation and might prove to be an effective adjunct to the therapies in vogue.
ABSTRACT
Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a pivotal role in the transformation and progression of tumors at all stages, especially during the invasion and metastasis. The aim of this study was to determine the genetic association of MMP2, MMP7 and MMP9 promoter polymorphisms with colorectal cancer (CRC) susceptibility and development risk in ethnic Kashmiri population. The genotype frequencies of MMP2-1306C/T, MMP7-181A/G and MMP9-1562C/T SNPs were compared between 142 CRC patients and 184 healthy controls by using PCR-RFLP method. The association between all the three MMP promoter polymorphisms and the modulation of risk of CRC was found to be significant (p≤0.05). The heterozygous genotype (CT) of MMP2-1306C/T SNP and variant genotype (GG) of MMP7-181A/G SNP showed a significant association with decreased risk for the development of CRC [OR, 0.61 (95%CI, 0.37-1.01); p=0.05 and OR, 0.43 (95%CI, 0.20-0.90); p=0.02, respectively] whereas the heterozygous genotype (CT) of MMP9-1562C/T SNP showed a significant association with increased risk for the development of colorectal cancer [OR, 1.88 (95%CI, 1.11-3.18); p=0.02]. Further, the less common MMP9-1562T allele was found to be significantly associated with an increased risk of colorectal cancer [OR, 1.74 (95%CI, 1.15-2.62); p=0.007]. Our results suggest that these MMP2, MMP7 and MMP9 promoter polymorphisms play a role as one of the key modulators of the risk of developing colorectal cancer in Kashmiri population.
