Abstract:
:Novel therapeutic strategies for breast cancer are urgently needed due to the sustained development of drug resistance and tumor recurrence. Trivalent arsenic derivative (arsenite, AsIII) has been reported to induce cytotoxicity in breast cancer cells. We recently demonstrated that AsIII plus tetrandrine (Tetra), a Chinese plant-derived alkaloid, exerted potent antitumor activity against human breast cancer cells, however, the underlying mechanisms for their action have not been well defined. In order to provide fundamental insights for understanding the action of AsIII plus Tetra, the effects of the combined regimen on two breast cancer cell lines T47D and MDA-MB-231 were evaluated. Compared to T47D cells, MDA-MB-231 cells were much more susceptible to the synergistic cytotoxic effects of AsIII and Tetra. Besides the induction of apoptotic/necrotic cell death, S-phase arrest and autophagic cell death were also observed in MDA-MB-231 cells. Exposure of MDA-MB-231 cells to AsIII and Tetra caused the activation of MAPKs. Cytotoxicity of the combined regimen in MDA-MB-231 cell was significantly abrogated by SP600125, a potent c-Jun N-terminal kinase (JNK) inhibitor. However, similar abrogation was not caused by p38 and ERK inhibitors. The addition of either autophagy inhibitors (3-methyladenine or wortmannin) or SP600125 corrected the combined regimen-triggered S-phase arrest, whereas had little effect on the apoptosis/necrosis induction in the cells. Surprisingly, SP600125NC, a negative control for SP600125, significantly strengthened S-phase arrest and the cytotoxicity induced by the combined regimen. The addition of SP600125 did not alter autophagy induction. In conclusion, the cytotoxicity of AsIII combined with Tetra was attributed to the induction of S-phase arrest, apoptotic/necrotic and autophagic cell death. The enhanced cytotoxicity of the two drugs by SP600125NC might be explained by its capability to strengthen S-phase arrest. Our results suggested that JNK and autophagy independently contributed to the cytotoxicity via modulating cell cycle progression. The study further provides fundamental insights for the development of AsIII in combination with Tetra for patients with different types of breast cancer.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Yu B,Yuan B,Li J,Kiyomi A,Kikuchi H,Hayashi H,Hu X,Okazaki M,Sugiura M,Hirano T,Fan Y,Pei X,Takagi Ndoi
10.3389/fphar.2020.01087subject
Has Abstractpub_date
2020-07-17 00:00:00pages
1087issn
1663-9812journal_volume
11pub_type
杂志文章abstract:Aims:SUMOylation is a post-translational modification that plays a crucial role in the cellular stress response. We aimed to demonstrate whether and how the SUMO E2 conjugation enzyme Ubc9 affects acute myocardial ischemic (MI) injury. Methods and Results:Adenovirus expressing Ubc9 was administrated by multipoint inje...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.561306
更新日期:2020-09-15 00:00:00
abstract:Background:Immunosuppressant non-adherence is a widespread problem among solid organ recipients. With the newly published clinical trials, the randomized controlled trials (RCTs) based systematic review of adherence-enhancing interventions on immunosuppressant adherence in solid organ recipients has not been completed....
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.578887
更新日期:2020-10-20 00:00:00
abstract::Fasudil, a Rho-kinase inhibitor, has shown outstanding therapeutic effects against cerebral vasospasm after subarachnoid hemorrhage (SAH) in humans. Studies show various biological effects of fasudil in the cardiovascular system. We conducted a preclinical systematic review to determine the efficacy and possible mecha...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01083
更新日期:2018-10-01 00:00:00
abstract::Gastric cancer is a common digestive tract tumor and the second most prevalent cancer. The prognosis of advanced gastric cancer is poor. Conversion therapy can reduce tumor burden, downgrade tumor, and increase the possibility of complete resection, thus prolonging the survival time of patients with gastric cancer. In...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.01027
更新日期:2020-07-14 00:00:00
abstract::Marantodes pumilum (Primulaceae) has been used in Malaysian folk medicine to help women regain strength after delivery and for "sickness in the bones." It was previously revealed that its extracts inhibited xanthine oxidase (XO) activity in vitro. The leaves and roots of M. pumilum var. alata (MPA), var. pumila (MPP),...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00289
更新日期:2020-03-17 00:00:00
abstract::Cancer is a common malignant disease worldwide with an increasing mortality in recent years. Salvia miltiorrhiza, a well-known traditional Chinese medicine, has been used for the treatment of cardiovascular and cerebrovascular diseases for thousands of years. The liposoluble tanshinones in S. miltiorrhiza are importan...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00193
更新日期:2020-03-19 00:00:00
abstract::Objective: Clinical trials are the source of evidence. ClinicalTrials.gov is valuable for analyzing current conditions. Until now, the state of drug interventions for heart infections is unknown. The purpose of this study was to comprehensively assess the characteristics of trials on cardiac-related infections and the...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00757
更新日期:2019-07-05 00:00:00
abstract::Striatal cholinergic interneurons (CINs) are the main source of acetylcholine in the striatum and are believed to play an important role in basal ganglia physiology and pathophysiology. The role of CINs in striatal function is known mostly from extracellular recordings of tonically active striatal neurons in monkeys, ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01488
更新日期:2019-12-13 00:00:00
abstract::Background: Rheumatoid arthritis is a type of systemic and complex autoimmune other disease characterized by chronic joint inflammation. Spleen tyrosine kinase (Syk) inhibitors are regarded as an effective alternative to existing drugs for the treatment of this disease. However, studies evaluating fostamatinib, a new ...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2019.00897
更新日期:2019-08-14 00:00:00
abstract::Tumor cells acquire invasive and metastatic behavior by sensing changes in the localization and activation of signaling pathways, which in turn determine changes in actin cytoskeleton. The core-scaffold machinery associated to β-arrestin (β-arr) is a key mechanism of G-protein coupled receptors (GPCR) to achieve spati...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00114
更新日期:2019-02-19 00:00:00
abstract::Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depr...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2014.00044
更新日期:2014-03-20 00:00:00
abstract::Many current chemotherapies function by damaging genomic DNA in rapidly dividing cells ultimately leading to cell death. This therapeutic approach differentially targets cancer cells that generally display rapid cell division compared to normal tissue cells. However, although these treatments are initially effective i...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00005
更新日期:2013-01-31 00:00:00
abstract::MOF is a well-known histone acetyltransferase to catalyze acetylation of histone H4 lysine 16 (K16), and it is relevant to diverse biological processes, such as gene transcription, cell cycle, early embryonic development and tumorigenesis. Here, we identify MOF as an oncogene in most thyroid cancer. It is found that e...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.607605
更新日期:2020-12-08 00:00:00
abstract::In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00196
更新日期:2017-05-08 00:00:00
abstract::Background: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC has shown its efficacy in adult tumor types such as breast and ovarian cancer and has to some extent been studied in pediatrics. Objecti...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00950
更新日期:2018-09-27 00:00:00
abstract::The mTOR signaling pathway is abnormally activated in pancreatic cancer and is related to tumor glucose metabolism. However, its specific regulation mechanism is still unclear. Therefore, this study aims to investigate whether Sestrin2 affects the glucose metabolism of pancreatic cancer by modulating mTOR signal and t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.580407
更新日期:2020-11-11 00:00:00
abstract::Targeting metabolic enzymes is believed to provide new therapeutic opportunities for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that importantly coordinates glycolysis, pentose phosphate pathway (PPP) flux and serine biosynthesis in cancer cells and hence gains increasing interest of inhi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00325
更新日期:2017-05-30 00:00:00
abstract::The objective of this study was to investigate the effect of human adipose tissue-derived mesenchymal stem cells (AdMSCs) on atopic dermatitis (AD) in the BALB/c mouse model. The AdMSCs attenuated clinical symptoms associated with AD, decreased numbers of degranulated mast cells (MCs), IgE level, amount of histamine r...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01175
更新日期:2018-11-06 00:00:00
abstract::The use of nanomaterials to modulate the tumor microenvironment has great potential to advance outcomes in patients with lung cancer. Nanomaterials can be used to prolong the delivery time of therapeutics enabling their specific targeting to tumors while minimizing and potentially eliminating cytotoxic effects. Using ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00759
更新日期:2018-07-16 00:00:00
abstract::Studies on the abuse potential of modafinil, a psychostimulant-like drug used to treat narcolepsy, are still controversial. While some studies claim no potential for abuse, increasing evidence suggests that modafinil induces abuse-related effects, including rapid-onset behavioral sensitization (i.e., a type of sensiti...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00211
更新日期:2019-03-11 00:00:00
abstract::Over the past several decades, natural products with poly-pharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Berberine (PubChem CID: 2353), a soliloquies quaternary alkaloid, has been validated to exert powerful effects in many cancers. However, the...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00857
更新日期:2019-08-06 00:00:00
abstract::The aim of this study was to investigate the regulatory function of the non-coding microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in alcoholic hepatitis (AH) and its potential mechanism associated with the mitogen-activated protein kinase (MAPK) signaling pathway. Levels of alanine aminotransfer...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00270
更新日期:2020-04-07 00:00:00
abstract::P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5'-RACE. A 1.9-kb fra...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00373
更新日期:2018-05-04 00:00:00
abstract::Objective: To evaluate therapeutic efficacy of different combined antimicrobial treatments against Acinetobacter baumannii ventilator-associated pneumonia (VAP). Methods: Clinical outcomes were retrospectively analyzed to elucidate the efficacy of four combined antimicrobial regimens. The chessboard and micro broth di...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00092
更新日期:2019-02-13 00:00:00
abstract::Arsenic is a toxic environmental contaminant. Long-term exposure to arsenic through drinking water induces human cancers. However, it is as yet uncertain about the mechanisms of arsenic induced carcinogenesis. Although the effects of low-dose arsenicals on proliferation and cell cycle have been revealed by short time ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01176
更新日期:2019-10-11 00:00:00
abstract::Cytochrome P450 enzymes are often responsible for the toxic and carcinogenic effects of toxicants, such as aflatoxin B1 (AFB1). The human hepatic CYP2A6 enzyme mediates the oxidative metabolism of several procarcinogens. In this study, we characterized a partial sequence of CYP2A6 gene from Arbor Acres (AA) broiler an...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00143
更新日期:2017-03-21 00:00:00
abstract::Benefiting from the continuously clarifying underlying biology of immune checkpoints and ligand-receptor interactions, the emergence of new anticancer treatment strategy, immunotherapy has shown substantial benefits on several liquid and solid tumors. Immune checkpoint inhibitors (ICIs) can block the negative regulato...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01254
更新日期:2019-10-23 00:00:00
abstract::Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00089
更新日期:2017-02-28 00:00:00
abstract::Chijabyukpi-tang (CBT) is an oriental herbal formula consisting of three herbs (Gardeniae Fructus (Gardenia jasminoides J.Ellis.), Phellodendri Cortex (Phellodendron amurense Rupr.), Glycyrrhizae Radix (Glycyrrhiza uralensis Fisch. ex DC.) at the ratio of 2: 2: 1. CBT has traditionally been used to treat eczema with i...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01018
更新日期:2020-07-07 00:00:00
abstract::Classically, the endocannabinoid system (ECS) consists of endogenous lipids, of which the best known are anandamide (AEA) and 2 arachidonoylglycerol (2-AG), their enzyme machinery for synthesis and degradation and their specific receptors, cannabinoid receptor one (CB1) and cannabinoid receptor two (CB2). However, end...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.596572
更新日期:2020-12-09 00:00:00