Abstract:
:Macroautophagy (hereafter referred to as autophagy) plays essential roles in cellular and organismal homeostasis. Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogenesis. It is not fully understood how the function of TFEB in autophagy pathway is regulated. Here, we show that Rac1 GTPase is a negative modulator of autophagy by targeting TFEB. Mechanistically, Rac1 reduces autophagy flux by repressing the expressing of autophagy genes. Further investigation revealed that under nutrient-rich conditions, mammalian target of rapamycin (mTOR) phosphorylates TFEB to facilitate the interaction between Rac1 and TFEB. Biochemical dissection uncovered that guanosine 5'-triphosphate (GTP)-bound form of Rac1 selectively interacts with phosphorylated TFEB. This inhibitory interaction prevents the dephosphorylation and nucleus translocation of TFEB, which hampers the transcriptional activation of autophagy-related genes. Furthermore, Rac1-TFEB axis appeared to be important for tumorigenesis, as overexpression of dephosphorylated mutant of TFEB was able to delay the tumor growth driven by Rac1 overexpression. Together, this study not only elucidates a previously uncharacterized autophagy regulation mechanism involving Rac1 and TFEB under physiological and pathological conditions but also suggests a strategy to treat cancers that are driven by Rac1 overexpression.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Ma L,Ma Y,Zhang Z,Wang Q,Liu Xdoi
10.1097/CAD.0000000000000816subject
Has Abstractpub_date
2019-11-01 00:00:00pages
1031-1037issue
10eissn
0959-4973issn
1473-5741journal_volume
30pub_type
杂志文章abstract::Caffeic acid phenethyl ester (CAPE) is a major propolis component that possesses a variety of pharmacological properties such as antioxidant and anticancer effects. Herein, we investigated the effectiveness of CAPE on cytotoxicity of clinically used anticancer drugs, doxorubicin (DXR) and cisplatin (CDDP), in parental...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000715
更新日期:2019-03-01 00:00:00
abstract::Matrix metalloproteinase (MMP)-2 and MMP-9 have been associated with the ability of tumor cells to metastasize because of their capacity to degrade type IV collagen, the main component of basement membrane, and to their elevated expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-((S)-2,6-dioxo-...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328313e15b
更新日期:2008-11-01 00:00:00
abstract::Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were de...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000934
更新日期:2020-08-01 00:00:00
abstract::Autophagy is a complex of adaptive cellular response that enhances cancer cell survival in the face of cellular stresses such as chemotherapy. Recently, chloroquine diphosphate (CQ), a widely used antimalarial drug, has been studied as a potential inhibitor of autophagy. Here, we aimed to investigate the role of CQ in...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328353f8c7
更新日期:2012-08-01 00:00:00
abstract::A patient with platinum resistant low-grade serous ovarian carcinoma had an objective response to therapy with bevacizumab and evidence of extended activity (>7 years). This case report adds to the growing literature regarding the use of bevacizumab in low-grade serous ovarian carcinoma. ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328363b64e
更新日期:2013-10-01 00:00:00
abstract::Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. We compared the activity of ARN versus bicalutamide on prostate cancer cell lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN and b...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000592
更新日期:2018-04-01 00:00:00
abstract::Oxaliplatin (L-OHP), irinotecan (CPT-11) and 5-fluorouracil (5-FU) have shown their efficacy in metastatic colorectal cancer. The synergism of these drugs has been demonstrated in vivo and in vitro. The aim of this study was to determine the recommended dose of the triple combination of L-OHP, CPT-11 and CI 5-FU for a...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/01.cad.0000127146.50172.8a
更新日期:2004-06-01 00:00:00
abstract::Metastases of prostate cancer originating from the parotid gland are rare. However, this presentation raises the question of the management of visceral metastasis in castration-resistant prostate cancer. We report the case of an 87-year-old man who presented with a right painless parotid mass in the context of castrat...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000188
更新日期:2015-03-01 00:00:00
abstract::We have synthesized and characterized doxorubicin (DOX)-loaded galactosylated gelatin nanovectors using in vitro and in vivo for targeting liver cells including hepatocarcinoma cells. Galactosylated and nongalactosylated gelatin nanovectors (GL-GN-DOX and GN-DOX) were spherical in shape and had mean sizes of about 95....
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328351424f
更新日期:2012-09-01 00:00:00
abstract::Treatment of mammalian cells with chemotherapeutic drugs can result in perturbations of nucleotide pools. Monitoring these perturbations in cultured tumor cells from human sources is useful for assessment of the effect of drug therapy and a better understanding of the mechanism of action of these drugs. In this study,...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000096
更新日期:2014-07-01 00:00:00
abstract::5-Fluorouracil (5-FU) is the most widely used agent for the management of colorectal cancer. Capecitabine is metabolized by three enzymatic actions, the last of which is mediated by thymidine phosphorylase, to produce 5-FU. Given the oral bioavailability of capecitabine as well as in-vitro and in-vivo findings showing...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3283441a63
更新日期:2011-04-01 00:00:00
abstract::In this study, we tried to define in vitro interactions of two antitumor agents that have different sites and different mechanisms of action. Vinblastine (VLB) in combination with human recombinant interferon-alpha A/D (rHuIFN-alpha A/D) and in combination with murine recombinant interferon-gamma (rMuIFN-gamma) was st...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199402000-00008
更新日期:1994-02-01 00:00:00
abstract::The use of viability assays to assess the effect of antineoplastic agents on cell lines and tumor cells is an important investigative tool and may have clinical relevance. Such assays require very small quantities of drugs and it is the practice of many laboratories to freeze aliquots of drugs for use in these assays ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199404000-00007
更新日期:1994-04-01 00:00:00
abstract::Trimetrexate (TMQ), a non-classical folate antagonist, was studied in a randomized controlled trial in patients with advanced colorectal cancer and without prior chemotherapy. Patients were randomly assigned to one of three treatments: TMQ at 200 mg/m2 i.v. q 2 weeks, TMQ at 12 mg/m2 i.v. daily x 5 or 5-fluorouracil (...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00001813-199504000-00004
更新日期:1995-04-01 00:00:00
abstract::We have previously reported the cytotoxic effects of chalcone A1, derived from 1-naphthaldehyde, in leukemia cell lines. On the basis of these findings, the main aim of this study was to elucidate some of the molecular mechanisms involved in apoptosis induced by chalcone A1 toward K562 and Jurkat cells. In both cell l...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000384
更新日期:2016-09-01 00:00:00
abstract::Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200606000-00007
更新日期:2006-06-01 00:00:00
abstract::The beta-carboline alkaloids are naturally existing plant substances. It is known that these alkaloids have a wide spectrum of neuropharmacological, psychopharmacological, and antitumor effects. Therefore, they have been traditionally used in oriental medicine for the treatment of various diseases including cancers an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32832a2dd9
更新日期:2009-06-01 00:00:00
abstract::The aim of this review is to summarize currently available information on the rapid screening and initial characterization of the different mechanisms of resistance to hydrophilic [e.g. methotrexate (MTX)] and lipophilic antifolates [e.g. trimetrexate (TMTX)] in cultured mammalian cells using fluorescein-methotrexate ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199310000-00002
更新日期:1993-10-01 00:00:00
abstract::Cantharidin is a natural toxin that possesses potent anti-tumor properties. Its clinical application, however, is limited due to severe side-effects. Its cytotoxicity is believed to be mediated by the inhibition of serine/threonine protein phosphatase 2A. In order to identify new compounds with potential clinical ther...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000217428.90325.35
更新日期:2006-09-01 00:00:00
abstract::A toxicology study of DENSPM was carried out in rats by multiple (once daily for 5 days) intravenous injection. Doses of 12.5, 25 and 50 mg DENSPM/kg were well tolerated. Infusion of 100 mg DENSPM resulted in distressing physical signs, including labored breathing, convulsive movements and acute death. There were no e...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199408000-00010
更新日期:1994-08-01 00:00:00
abstract::Metformin, an oral antidiabetic agent, has been reported to potentiate chemotherapeutic-induced cytotoxicity. In this study, we investigated the effects and molecular mechanisms of metformin in sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human bladder cancer cells. ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000116
更新日期:2014-09-01 00:00:00
abstract:UNLABELLED:Thirty-two evaluable patients with squamous cell cancer of the cervix were treated with i.v. paclitaxel 250 mg/m2 over 3 h every 21 days. They received standard premedications and granulocyte colony stimulating factor (G-CSF) support (5 micrograms/kg/day). Median (range) age was 49 (29-81) years and performa...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199708000-00002
更新日期:1997-08-01 00:00:00
abstract::A phase I/II study to determine the recommended dose for combination therapy with CPT-11 (irinotecan hydrochloride) and S-1 (tegafur, gimestat and otastat potassium) for advanced or recurrent gastric cancer, and to assess the safety and efficacy of this therapy. In the phase I portion of the study, S-1 was administere...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3280262460
更新日期:2007-06-01 00:00:00
abstract::Heavy water (deuterium oxide: D2O) contains a neutron and a proton in its hydrogen atoms and shows a variety of biologic activities different from normal light water. In the present study the cytotoxic and cytostatic activity of D2O was assessed using a BALB/c-3T3 fibroblast cell line and four human digestive organ ca...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199809000-00007
更新日期:1998-09-01 00:00:00
abstract::We have examined the biological activity of keto-C-glycosides (KCGs), a new family of drugs displaying antiproliferative and cytotoxic properties on tumor cells. KCG1, the most powerful drug tested on epithelial derived neoplastic cells, was 25-125 times more cytostatic on epithelial cells than on lymphoma. By contras...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199208000-00006
更新日期:1992-08-01 00:00:00
abstract::The aim of the present study was to investigate the gene expression of biomarkers associated with the sensitivity to fluoropyrimidine and taxanes in recurrent/advanced breast cancer patients treated with first-line capecitabine chemotherapy. We evaluated the clinicopathological/prognostic significance of thymidylate s...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32834f7ef4
更新日期:2012-06-01 00:00:00
abstract::Long noncoding RNA (lncRNA) KTN1 antisense RNA 1 (KTN1-AS1) is a novel promoter in the progression of some cancers. However, the knowledge of its role in lung adenocarcinoma is still limited. The current study aimed to examine the biological functions of KTN1-AS1 and its coexpressed protein in lung adenocarcinoma. The...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000001035
更新日期:2021-01-22 00:00:00
abstract::Metastatic meningioma is a rare disease, which has no effective chemotherapy. We report on a treatment of this condition with Doxil, a liposomal doxorubicin formulation. A 60-year-old woman with massive pleuro-pulmonary metastases from recurrent cranial meningioma was treated with Doxil (50-37.5 mg/m2) for 18 months w...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200303000-00009
更新日期:2003-03-01 00:00:00
abstract::Fibroblast growth factor-inducible 14 (Fn14) has been reported to play an oncogene role in many types of cancer. However, its biological functions in small-cell lung cancer (SCLC) remain unknown. The aim of this study is to investigate the roles of Fn14 in the cell growth and chemoresistance of SCLC and its possible m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000153
更新日期:2014-11-01 00:00:00
abstract::Our objective was to determine the maximum tolerated dose (MTD) of paclitaxel when given as a 7 day continuous i.v. infusion, repeated every 3 weeks, and to evaluate the toxicity and the efficacy of such a schedule of administration as a salvage treatment in ovarian cancer patients pretreated and refractory to 3 or 24...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199709000-00005
更新日期:1997-09-01 00:00:00