RESUMO
Kidney cancer has emerged as a major medical problem in recent times. Multiple compounds are used to treat kidney cancer by triggering cancer-causing gene targets. For instance, isoquercitrin (quercetin-3-O-ß-d-glucopyranoside) is frequently present in fruits, vegetables, medicinal herbs, and foods and drinks made from plants. Our previous study predicted using protein-protein interaction (PPI) and molecular docking analysis that the isoquercitrin compound can control kidney cancer and inflammation by triggering potential gene targets of IGF1R, PIK3CA, IL6, and PTGS2. So, the present study is about further in silico and in vitro validation. We performed molecular dynamic (MD) simulation, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, cytotoxicity assay, and RT-PCR and qRT-PCR validation. According to the MD simulation (250 ns), we found that IGF1R, PIK3CA, and PTGS2, except for IL6 gene targets, show stable binding energy with a stable complex with isoquercitrin. We also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the final targets to determine their regulatory functions and signaling pathways. Furthermore, we checked the cytotoxicity effect of isoquercitrin (IQ) and found that 5 µg/mL and 10 µg/mL doses showed higher cell viability in a normal kidney cell line (HEK 293) and also inversely showed an inhibition of cell growth at 35% and 45%, respectively, in the kidney cancer cell line (A498). Lastly, the RT-PCR and qRT-PCR findings showed a significant decrease in PTGS2, PIK3CA, and IGF1R gene expression, except for IL6 expression, following dose-dependent treatments with IQ. Thus, we can conclude that isoquercitrin inhibits the expression of PTGS2, PIK3CA, and IGF1R gene targets, which in turn controls kidney cancer and inflammation.
RESUMO
Pancreatic ductal adenocarcinoma (PDAC) has naturally aggressive characteristics including postoperative recurrence, resistance to conventional treatment, and metastasis. Surgical resection with chemotherapeutic agents has been conducted as the major treatment for PDAC. However, surgical treatment is ineffective in the case of advanced cancer, and conventional adjuvant chemotherapy, including gemcitabine and 5-fluorouracil, show low effectiveness due to the high drug resistance of PDAC to this type of treatment. Therefore, the development of innovative therapeutic drugs is crucial to solving the present limitation of conventional drugs. Glucotropaeolin (GT) is a glucosinolate that can be isolated from the Brassicaceae family. GT has exhibited a growth-inhibitory effect against liver and colon cancer cells; however, there is no study regarding the anticancer effect of GT on PDAC. In our study, we determined the antiproliferative effect of GT in PANC-1 and MIA PaCa-2, representative of PDAC. We revealed the intracellular mechanisms underlying the anticancer effect of GT with respect to cell viability, reactive oxygen species (ROS) accumulation, alteration of mitochondrial membrane potential (MMP), calcium dysregulation, cell migration, and the induction of apoptosis. Moreover, GT regulated the signaling pathways related to anticancer in PDAC cells. Finally, the silencing of the forkhead box protein M, a key factor regulating PDAC progression, contributes to the anticancer property of GT in terms of the induction of apoptosis and cell migration. Therefore, GT may be a potential therapeutic drug against PDAC.
RESUMO
BACKGROUND: Phytosterols have physiological effects and are used as medicines or food supplements. Stigmasterol has shown anticancer effects against various cancers such as hepatoma, cholangiocarcinoma, gall bladder carcinoma, endometrial adenocarcinoma and skin, gastric, breast, prostate, and cervical cancer. However, there are no reports on stigmasterol's effects on ovarian cancer. METHODS: We investigated the effects of stigmasterol on proapoptotic signals, mitochondrial function, reactive oxygen species production, and the cytosolic and mitochondrial calcium levels in human ovarian cancer cells, to understand the mechanisms underlying the effects of stigmasterol on ovarian cancer cells. We also conducted migration assay to confirm whether that stigmasterol inhibits ovarian cancer cell migration. RESULTS: Stigmasterol inhibited development of human ovarian cancer cells. However, it induced cell apoptosis, ROS production, and calcium overload in ES2 and OV90 cells. In addition, stigmasterol stimulated cell death by activating the ER-mitochondrial axis. We confirmed that stigmasterol suppressed cell migration and angiogenesis genes in human ovarian cancer cells. CONCLUSIONS: Our findings suggest that stigmasterol can be used as a new treatment for ovarian cancer.
RESUMO
Ovarian cancer (OC) is difficult to diagnose at an early stage and leads to the high mortality rate reported in the United States. Standard treatment for OC includes maximal cytoreductive surgery followed by platinum-based chemotherapy. However, relapse due to chemoresistance is common in advanced OC patients. Therefore, it is necessary to develop new anticancer drugs to suppress OC progression. Recently, the anticancer effects of laminarin, a beta-1,3-glucan derived from brown algae, have been reported in hepatocellular carcinoma, colon cancer, leukemia, and melanoma. However, its effects in OC are not reported. We confirmed that laminarin decreases cell growth and cell cycle progression of OC cells through the regulation of intracellular signaling. Moreover, laminarin induced cell death through DNA fragmentation, reactive oxygen species generation, induction of apoptotic signals and endoplasmic reticulum (ER) stress, regulation of calcium levels, and alteration of the ER-mitochondria axis. Laminarin was not cytotoxic in a zebrafish model, while in a zebrafish xenograft model, it inhibited OC cell growth. These results suggest that laminarin may be successfully used as a novel OC suppressor.