“…identified that C6-8, an aptamer targeting ROS17/2.8 cells, could specifically bind to hnRNPA2/B1 and precisely label multiple cancer cell lines with fluorescent carbon nanodots (CDots) conjugation. In addition, hnRNPA2/B1 has also been discovered as a direct target candidate for tamoxifen analog Ridaifen-G (RID-G) in its potent anticancer working [ 125 ]. Fig.…”
Section: The Roles Of Hnrnpa/b In Cancers: Molecular Mechanisms and C...mentioning
Heterogeneous nuclear ribonucleoprotein A/B (hnRNPA/B) is one of the core members of the RNA binding protein (RBP) hnRNPs family, including four main subtypes, A0, A1, A2/B1 and A3, which share the similar structure and functions. With the advance in understanding the molecular biology of hnRNPA/B, it has been gradually revealed that hnRNPA/B plays a critical role in almost the entire steps of RNA life cycle and its aberrant expression and mutation have important effects on the occurrence and progression of various cancers. This review focuses on the clinical significance of hnRNPA/B in various cancers and systematically summarizes its biological function and molecular mechanisms.
“…identified that C6-8, an aptamer targeting ROS17/2.8 cells, could specifically bind to hnRNPA2/B1 and precisely label multiple cancer cell lines with fluorescent carbon nanodots (CDots) conjugation. In addition, hnRNPA2/B1 has also been discovered as a direct target candidate for tamoxifen analog Ridaifen-G (RID-G) in its potent anticancer working [ 125 ]. Fig.…”
Section: The Roles Of Hnrnpa/b In Cancers: Molecular Mechanisms and C...mentioning
Heterogeneous nuclear ribonucleoprotein A/B (hnRNPA/B) is one of the core members of the RNA binding protein (RBP) hnRNPs family, including four main subtypes, A0, A1, A2/B1 and A3, which share the similar structure and functions. With the advance in understanding the molecular biology of hnRNPA/B, it has been gradually revealed that hnRNPA/B plays a critical role in almost the entire steps of RNA life cycle and its aberrant expression and mutation have important effects on the occurrence and progression of various cancers. This review focuses on the clinical significance of hnRNPA/B in various cancers and systematically summarizes its biological function and molecular mechanisms.
“…Examples include a plant-derived natural product oxymatrine to treat chronic hepatitis B (CHB) [66], a lipocyclodepsipeptide MA026 that shows anti-hepatitis C virus (HCV) activity [67]. Off-target for conventional anti-cancer compounds, such as α-SQMG, camptothecin (CPT), etoposide (Etp), or doxorubicin [68][69][70][71], as well as for anti-tumor compounds with unique mechanism (CBP501, daptomycin, 11-aza-artemisinin, estradiol or Ridaifens) were identified [72][73][74][75][76][77]. Furthermore, following bioactive compounds were used for phage display biopanning as bait; tumor hypoxia-targeting LW6 [78], antiangiogenic methylsynephrine or PFOS [79,80], simvastatin and fluvastatin used to treat cardiovascular disease [81], flavonoid analogues [82], an inhibitor for plant hormone biosynthesis (Brz2001) [83], or the rice blast fungus differentiation (roxithromycin) or appressorium formation (chloramphenicol) [84,85], neuroprotective agents (neoechinulin A) [86], and central nervous system stimulants [87].…”
Introduction: Our understanding of the mechanism of action of bioactive small molecules contributes to the research and development of new medical drugs, as well as elucidating the pathological mechanisms underlying various diseases. Researchers in this field are committed to a very ambitious goal: the discovery of novel therapeutic compounds along with their molecular targets. To achieve this goal, new methodological developments are indispensable.Areas covered: This review gives an update on the advancements of phage display (PD) technology in the past decade (2011-2020) for determining the targets of the small molecule therapeutics. In particular, other than providing a brief overview of this field of research, we focus on reporting the research trends and the results solely obtained using this strategy. Expert opinion: Despite the development of bioinformatics tools and artificial intelligence (AI)mediated methods, affinity-guided information obtained experimentally are still indispensable to identify drug-protein interactions. By taking advantage of small-molecule-oriented PD methods and their improvements, the extension of the druggable proteome will be further expanded, providing new opportunities to generate small-molecule therapeutics.
“…Furthermore, the mechanism of RID-mediated cancer cell growth inhibition may differ from that of currently used anti-cancer drugs, indicated by COMPARE analysis (4). One of the RIDs, RID-G, could induce caspase-independent atypical cell death involving mitochondrial dysfunction in human neoplastic hematopoietic cell lines (5), and has been indicated to interact with calmodulin, heterogeneous nuclear ribonucleoproteins A2/B1 and zinc finger protein 638 during its cancer cell growth inhibition (6). RID-F may serve as a proteasome inhibitor, and inhibit chymotrypsin-like, trypsin-like and peptidylglutamyl peptide hydrolase activities (7,8).…”
Abstract. Ridaifens (RIDs), a novel series of tamoxifen derivatives, exhibit a potent growth-inhibitory effect against numerous tumor cells regardless of the expression of estrogen receptors, and are thus promising candidates as novel anti-tumor drugs. RID-B is a first generation RIDs, and inhibits the proliferation of several tumor cell lines. However, the potentially growth inhibitory effect of RID-B against hepatoma cells, and the detailed mechanism underlying RID-B-mediated tumor cell death remain to be elucidated. The purpose of the current study was to evaluate the anti-proliferative effect of RID-B against hepatoma cells. The anti-proliferative effect of RID-B against human hepatoma Huh-7 cells was investigated by cell proliferation assay using WST-1 reagent, and caspase-3 activity was evaluated by using specific fluorescent substrate. In addition, DNA fragmentation in Huh-7 cells induced by RID-B was estimated by terminal deoxynucleotidyl transferase dUTP nick-end labelling assay, and binding of RID-B to double-stranded DNA was confirmed by mass spectrometry. RID-B (0.5, 1 and 2 µM) inhibited the growth of Huh-7 cells, seemingly dose-dependently, but did not inhibit the growth of normal primary rat hepatocytes in the same concentration range. Furthermore, the caspase-3 activity of Huh-7 cells was increased by RID-B (0.5 and 5 µM), and the anti-proliferative effect of RID-B (1 µM) on Huh-7 cells was partially suppressed by the addition of the caspase inhibitor, Z-VAD-FMK. Additionally, RID-B (10 µM) directly bound to double-stranded DNA, and the addition of DNA suppressed RID-B-mediated cell growth inhibition and DNA fragmentation in Huh-7 cells. From these data, it may be concluded that RID-B inhibited cell growth and induced apoptosis via activating caspase-3 and binding to DNA directly, leading to DNA fragmentation in hepatoma cells.
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