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Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2 (CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal-regulated kinase 1/2, and disrupting the repair process of DNA double-strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA)-mutant CRC, resulting in a reduction in phosphatidylinositol-3 kinase (PI3K) expression, Ak strain transforming phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.
RESUMO
Colon cancer (CC) is one of the most common and deadly cancers worldwide. Oncologists are facing challenges such as development of drug resistance and lack of suitable drug options for CC treatment. Flavonoids are a group of natural compounds found in fruits, vegetables, and other plant-based foods. According to research, they have a potential role in the prevention and treatment of cancer. Apigenin is a flavonoid that is present in many fruits and vegetables. It has been used as a natural antioxidant for a long time and has been considered due to its anticancer effects and low toxicity. The results of this review study show that apigenin has potential anticancer effects on CC cells through various mechanisms. In this comprehensive review, we present the cellular targets and signaling pathways of apigenin indicated to date in in vivo and in vitro CC models. Among the most important modulated pathways, Wnt/ß-catenin, PI3K/AKT/mTOR, MAPK/ERK, JNK, STAT3, Bcl-xL and Mcl-1, PKM2, and NF-kB have been described. Furthermore, apigenin suppresses the cell cycle in G2/M phase in CC cells. In CC cells, apigenin-induced apoptosis is increased by inhibiting the formation of autophagy. According to the results of this study, apigenin appears to have the potential to be a promising agent for CC therapy, but more research is required in the field of pharmacology and pharmacokinetics to establish the apigenin effects and its dosage for clinical studies.
RESUMO
BACKGROUND: The etiology of LARS has not been elaborated on clearly. Studies have reported neoadjuvant therapy, low-lying rectal cancers, adjuvant therapy and anastomotic leakage as risk factors for the development of LARS. Anastomotic level has also been proposed as a possible risk factor; However, there have been conflicting results. This study aims to evaluate the role of the level of anastomosis as a potential risk factor for the development of LARS. METHOD: A systematic literature search was conducted on Pubmed, Scopus, Embase, and Web of Science databases using Mesh terms and non-Mesh terms from 2012 to 2023. Original English studies conducted on rectal cancer patients reporting of anastomotic level and LARS status were included in this study. Eligible studies were assessed regarding quality control with Joanna-Briggs Institute (JBI) questionnaires. RESULTS: A total of 396 articles were found using the research queries, and after applying selection criteria 4 articles were selected. A sample population of 808 patients were included in this study with a mean age of 61.51 years with male patients consisting 59.28% of the cases. The Mean assessment time was 15.6 months which revealed a mean prevalence of 48.89% for LAR syndrome. Regression analysis revealed significantly increased risk of LAR syndrome development due to low anastomosis level in all 4 studies with odds ratios of 5.336 (95% CI:3.197-8.907), 3.76 (95% CI: 1.34-10.61), 1.145 (95% CI: 1.141-2.149) and 2.11 (95% CI: 1.05-4.27) for low anastomoses and 4.34 (95% CI: 1.05-18.04) for ultralow anastomoses. CONCLUSIONS: LARS is a long-term complication following surgery, leading to reduced quality of life. Low anastomosis level has been reported as a possible risk factor. All of the studies in this systematic review were associated with an increased risk of LARS development among patients with low anastomosis.