Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy

Abstract

Objective: Gastric cancer is the fourth most common cancer and the second cause of death in the world. According to the studies, the gastric cancer is relatively sensitive to chemotherapy. The aim of this study was to investigate the association of oral administer PUFAs with Caspase enzymes in patients with gastric cancer under chemotherapy. Methods: This study was a Clinical Trial in which the target group consisted of the patients recognized with gastric cancer for the first time and cured under chemotherapy. Thirty-four patients were selected and categorized randomly into two groups. The case group included the patients taking PUFAs along with chemotherapeutic agent. In these patients, chemotherapy started with Cis-Platin plus PUFAs supplement in the scale of 3600 mg daily and in three courses. In control group, the individuals were under the same chemotherapy protocol without PUFAs. Biopsy samples from tumor were taken from the patients before and after chemotherapy. Levels of mRNA and protein expression of caspase 3, 8, 9 were measured in biopsy samples by Real-Time PCR and Frozen Section methods. The levels of apoptosis were determined using DNA-damage colorimetric assay. Results: In the case group, caspase 3 showed a significant increase in both gene and protein expression levels after administration of PUFAs supplement in comparison with those of the control group (p=0.006 for gene, p=0.001 for protein). PUFAs induced caspase-9 gene expression level in these patients (p<0.0001). Caspase-9 protein level also revealed a marked elevation when PUFAs were administered along with chemotherapeutic agent (p<0.0001). DNA damage in gastric tissue from the patients under PUFAs treatment plus Cis-Platin was significantly higher than that of control group (p=0.003). PUFAs showed no significant changes in caspase-8 both at the gene and protein levels in the patients. Conclusion: According to the results of present study, it appears that oral administration of PUFAs can elevate the efficacy of chemotherapy agent in individuals' mitochondria-dependent apoptosis. As PUFAs enhances caspase-3 and 9 genes expression levels, which is an important induce the mitochondrial dependent apoptosis process. The study was registered in Iran clinical trials registry center under No. IRCT2014031016922N1.

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“…The caspase family has >10 members which are among the most important factors in the apoptotic process (17). The members of the caspase family serve distinct functions in the apoptotic pathway, in which caspase-2, -8, -9 and -10 are primarily involved in the initiation of apoptosis (17).…”

“…The caspase family has >10 members which are among the most important factors in the apoptotic process (17). The members of the caspase family serve distinct functions in the apoptotic pathway, in which caspase-2, -8, -9 and -10 are primarily involved in the initiation of apoptosis (17). Caspase-3, -6 and -7 may be combined with a variety of substrates for hydrolysis, leading to chromatin condensation and nuclear disintegration, and are therefore apoptosis executioner proteins (18).…”

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“…Caspase-8 and caspase-9 and caspase-3 are apoptotic promoters and an apoptotic effector, respectively. After activation by upstream signalling, including caspase-2, caspase-9, and caspase-10, caspase-3 can lyse extracellular substances and cytoskeleton protein or poly ADP-ribose polymerase and other DNA repair-related molecules to induce the apoptosis of tumour cells [20,21]. The level of the ratio of Bax/Bcl-2 mRNA plays an important role in the apoptosis of tumour cells.…”