isoquercitrin and Urinary-Bladder-Neoplasms

Cancer cells are well known to require a constant supply of protein, lipid, RNA, and DNA via altered metabolism for accelerated cell proliferation. Targeting metabolic pathways is, therefore, a promising therapeutic strategy for cancers. Isoquercitrin (ISO) is widely distributed in dietary and medicinal plants and displays selective cytotoxicity to cancer cells, primarily by inducing apoptosis and cell cycle arrest. The aims of this study were to find out whether ISO could stabilize in a bladder-like acidic environment and inhibit bladder cancer cell proliferation by affecting their metabolism, and to investigate its molecular mechanism. In this study, the exposure of T24 bladder cancer cells to ISO (20-80 μM) decreased cell viability by causing ROS overproduction. This ROS change regulated the AMPK signaling pathway, and caused Caspase-dependent apoptosis as well as metabolism dysfunction. Metabolic alterations elevated metabolic pathway variation, which in turn destabilized lipid synthesis and altered anaerobic glycolysis. This linkage was proved by immunoblotting assay, and metabolomics as identified by UHPLC-QTOF-MS. Our findings provide comprehensive evidence that ISO influenced T24 bladder cancer cell metabolism, and that this process was mainly involved in activating the AMPK pathway. This study could lead to an understanding of how ISO suppresses bladder cancer cell growth, and whether the affected cancer metabolism is a common mechanism by which nutritional compounds suppress cancers.

Topics: AMP-Activated Protein Kinase Kinases; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Protein Kinases; Quercetin; Reactive Oxygen Species; Signal Transduction; Urinary Bladder Neoplasms

Research studies in recent years have found that isoquercetin has an inhibiting effect on multiple carcinogens, but research studies filed on isoquercetin in bladder cancer are quite few. This paper observed the influence of isoquercetin on biological activity of the EJ cell of bladder cancer through HC dyeing and trypan blue counting, studied the EJ cell cycle by flow cytometry (FCM), and then analyzed the influence of isoquercetin and its effect on the protein expression of STAT3 and STAT3-inhibiting factors (PIAS3) in EJ cells. Research has shown that isoquercetin has an inhibitory effect on the EJ cells of bladder cancer, but it is not obvious.

Topics: Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Molecular Chaperones; Neoplasm Proteins; Plants, Medicinal; Protein Inhibitors of Activated STAT; Quercetin; STAT3 Transcription Factor; Urinary Bladder Neoplasms

Bladder cancer is the most common malignancy of the urinary system and is also one of the 10 most common cancers of the human body. Currently, clinical treatment of bladder cancer mainly utilizes partial or total cystectomy, supplemented by conventional chemotherapy. However, such treatment has not fully improved the prognosis of patients and is associated with various side effects. Studies have found that flavonoids extracted from plants can be used in radiotherapy and chemotherapy for the prevention of postoperative recurrence and metastasis but also alone for the treatment of advanced tumors. Both applications can ameliorate clinical symptoms, improve the quality of life, and prolong the survival of patients. Based on the above information, the present study investigated the effect of isoquercitrin, a type of flavonoid found in Bidens pilosa L. extracts, on bladder cancer progression, with the goal of understanding the biological characteristics of isoquercitrin by which it participates in bladder cancer progression. Using in vitro experiments, we found that therapeutic doses of isoquercitrin significantly inhibited cell proliferation and induced apoptosis in human bladder cancer cells and that the cell cycle was arrested in the G1 phase. Isoquercitrin inhibited phosphatidylinositol 3-kinase (PI3K) and Akt phosphorylation expression levels, thus inhibiting proliferation and inducing apoptosis in the cancer cells. In addition, we found that isoquercitrin reduced protein kinase C (PKC) protein expression levels in the human bladder cancer cell lines. We also showed via in vivo experiments that isoquercitrin inhibited xenograft tumor growth in nude mice. In conclusion, our study confirmed that isoquercitrin inhibits bladder cancer progression in vivo and demonstrated that the molecular mechanism of this inhibition may be closely associated with the PI3K/Akt and PKC signaling pathways.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Progression; G1 Phase Cell Cycle Checkpoints; Humans; Male; Mice; Mice, Nude; Phosphatidylinositol 3-Kinase; Phosphorylation; Protein Kinase C; Proto-Oncogene Proteins c-akt; Quercetin; Signal Transduction; Urinary Bladder; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays