Resistance of colon cancer to 5-fluorouracil may be overcome by combination with chloroquine, an in vivo study.

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 potentiating the effect of 5-fluorouracil (5-FU), the chemotherapeutic agent of first choice for the treatment of colorectal cancer, in an animal model of colon cancer. The mouse colon cancer cell line colon26 was used. For the in-vivo study, colon26 cells were injected subcutaneously into BALB/c mice, which were treated with saline as a control, CQ (50 mg/kg/day), 5-FU (30 mg/kg/day), or the combination therapy (CQ plus 5-FU). The tumor volume ratio and body weight were monitored. After the sacrifice, tumor tissue protein extracts and tumor sections were prepared and subjected to immunoblotting for the analysis of autophagy-related and apoptosis-related proteins, and the terminal transferase uridyl end labeling assay. The combination of CQ resulted in the inhibition of 5-FU-induced autophagy and a significant enhancement in the 5-FU-induced inhibition of tumor growth. Furthermore, the combination treatment of CQ and 5-FU resulted in a significant increase in the ratio of apoptotic cells compared with other treatments. The expression levels of the proapoptotic proteins, namely Bad and Bax, were increased by the CQ treatment in the protein extracts from tumors. Our findings suggest that the combination therapy of CQ and 5-FU should be considered as an effective strategy for the treatment of colorectal cancer.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Sasaki K,Tsuno NH,Sunami E,Kawai K,Hongo K,Hiyoshi M,Kaneko M,Murono K,Tada N,Nirei T,Takahashi K,Kitayama J

doi

10.1097/CAD.0b013e328353f8c7

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

675-82

issue

7

eissn

0959-4973

issn

1473-5741

journal_volume

23

pub_type

杂志文章
  • Rectovaginal fistula during treatment with axitinib in a patient with renal cell carcinoma: a case report and review of the literature.

    abstract::Renal cell carcinoma (RCC) is one of the most frequent malignancies of the adults. Its incidence has been increasing steadily by 2-4% each year. Up to 30% of patients present with metastases at diagnosis. It is a highly vascularized cancer because of the hypoxia-induced factor stabilization as a consequence of von Hip...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0000000000000742

    authors: Nigro O,Pastore A,Tartaro T,Bolzacchini E,Tuzi A,Pinotti G

    更新日期:2019-04-01 00:00:00

  • Synergistic killing effect of imatinib and simvastatin on imatinib-resistant chronic myelogenous leukemia cells.

    abstract::The antiproliferative effect of simvastatin on tumor cells has been speculated to be by intracellular signal inhibition through 3-hydroxy-3-methylglutaryl acetyl coenzyme A reductase. We examined the killing effect of simvastatin on imatinib-sensitive and resistant chronic myelogenous leukemia (CML) cells (three kinds...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32835a0fbd

    authors: Oh B,Kim TY,Min HJ,Kim M,Kang MS,Huh JY,Kim Y,Lee DS

    更新日期:2013-01-01 00:00:00

  • Mutational profile in circulating tumor DNA in a patient affected by low-risk endometrial cancer: predictable tool of relapse?

    abstract::Endometrial cancer is the commonest gynecological cancer, the majority is endometrioid type, diagnosed at an early stage with 69-88% 5-year survival. Low-grade endometrial cancers have low recurrence rates and often do not receive adjuvant therapy; however, a subset of these patients will have poor outcomes and would ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000963

    authors: Malentacchi F,Turrini I,Zepponi F,Fantappiè G,Sorbi F,Antonuzzo L,Fambrini M,Noci I,Pillozzi S

    更新日期:2020-11-01 00:00:00

  • Response by Choi criteria to sunitinib plus octreotide LAR in a functional heavily pretreated advanced pancreatic neuroendocrine tumor.

    abstract::Pancreatic neuroendocrine tumors (PNETs) are rare malignancies that arise from the islets of Langerhans. The role of standard chemotherapy in advanced well-differentiated PNETs remains to be defined. Sunitinib is an oral multitargeted inhibitor with antiangiogenic and antitumor properties that has shown significant im...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328344484b

    authors: Grande E,José Díez J,Pachón V,Angeles Vaz M,Longo F,Guillén C,García de Paredes ML,Carrato A

    更新日期:2011-06-01 00:00:00

  • Variable intrinsic sensitivity of human tumor cell lines to raltitrexed (Tomudex) and folylpolyglutamate synthetase activity.

    abstract::The cytotoxic effects of Tomudex (TX) were investigated on a panel of 15 human tumor cell lines expressing a spontaneous sensitivity to the tested agent. We determined the basal cellular amount of relevant cellular factors potentially related to the cytotoxic efficacy of or resistance to TX. We selected thymidylate sy...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199906000-00010

    authors: Chéradame S,Chazal M,Fischel JL,Formento P,Renée N,Milano G

    更新日期:1999-06-01 00:00:00

  • Docetaxel: an interesting new drug for the treatment of head and neck cancers and soft tissue sarcomas.

    abstract::Results are summarized for two phase II studies of docetaxel as first-line therapy for advanced squamous cell carcinoma of the head and neck (SCCHN) and one study of docetaxel as second-line therapy for advanced soft tissue sarcomas. In all three studies, docetaxel was administered at a dose of 100 mg/m2 by intravenou...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1097/00001813-199507004-00004

    authors: Verweij J

    更新日期:1995-07-01 00:00:00

  • NCPMF-60 induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.

    abstract::We recently established that NCPMF-60, a newly synthesized flavonoid, is an active cytotoxic component. The molecular mechanisms by which NCPMF-60 exerts its cytotoxic activity are currently unknown. In this study, we show that NCPMF-60 induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 ce...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3283405801

    authors: Dai QS,Liu W,Wang XB,Lu N,Gong DD,Kong LY,Guo QL

    更新日期:2011-01-01 00:00:00

  • Phase I trial of weekly irinotecan and paclitaxel combined with carboplatin in patients with advanced cancer: a Hellenic Cooperative Oncology Group Study.

    abstract::This trial aimed to define a recommended safe dose (RSD) of weekly paclitaxel and irinotecan combined with carboplatin in patients with advanced cancer. Patients with advanced cancer were eligible for this trial. Dose-limiting toxicity (DLT) was considered to be any grade greater than or equal to 3 (G> or =3) nonhemat...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32833d5ec0

    authors: Briasoulis E,Golfinopoulos V,Karina M,Papakostas P,Pavlidis N,Fountzilas G

    更新日期:2010-09-01 00:00:00

  • Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines.

    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

    authors: Koukourakis MI,Kakouratos C,Kalamida D,Mitrakas A,Pouliliou S,Xanthopoulou E,Papadopoulou E,Fasoulaki V,Giatromanolaki A

    更新日期:2018-04-01 00:00:00

  • Schlafen-11 sensitizes colorectal carcinoma cells to irinotecan.

    abstract::Schlafen-11 (SLFN11) showed a highly significant positive correlation with the response of topoisomerase inhibitors in cancer cell lines derived from prostate, lung, etc. However, this finding has not been validated in colorectal cancers (CRCs). Although irinotecan (CPT-11), a topoisomerase inhibitor, is one of the mo...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000151

    authors: Tian L,Song S,Liu X,Wang Y,Xu X,Hu Y,Xu J

    更新日期:2014-11-01 00:00:00

  • Apoptosis induced by desmethyl-lasiodiplodin is associated with upregulation of apoptotic genes and downregulation of monocyte chemotactic protein-3.

    abstract::There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by end...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3283635a47

    authors: Hazalin NA,Lim SM,Cole AL,Majeed AB,Ramasamy K

    更新日期:2013-09-01 00:00:00

  • Evaluation of certain ureas and nitrosoureas of 2,3-dihydro-1,4-benzothiazines against Sarcoma-180 solid tumors in vivo.

    abstract::Different derivatives of nitrosoureas were synthesized by a long sequence of reactions and were evaluated for their anticancer activities against female Swiss albino mice, 6-8 weeks old, weighing 18-24 g and bearing Sarcoma-180 (S-180) ascitic tumor. Experimental protocols include injecting a total of 2 x 10(5) S-180 ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199510000-00009

    authors: Nyati MK,Rajoria CM,Gupta RR,Dev PK

    更新日期:1995-10-01 00:00:00

  • A suramin derivative induces enterocyte-like differentiation of human colon cancer cells without lysosomal storage disorder.

    abstract::Suramin is a polysulfonated naphthylurea currently investigated for the treatment of advanced malignancy. We have previously reported that suramin was a potent inducer of the differentiation of the human colic adenocarcinoma cell clone HT29-D4 (Fantini et al., J Biol Chem, 1989; 264: 10282-10286). In this report, we s...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199010000-00011

    authors: Baghdiguian S,Nickel P,Marvaldi J,Fantini J

    更新日期:1990-10-01 00:00:00

  • Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivity.

    abstract::Chemotherapy for breast cancer is given on the basis of empirical information from clinical trials, an approach which falls to take into account the known heterogeneity of chemosensitivity between patients. Previous attempts to determine chemosensitivity ex vivo have been disappointing, but in this study results from ...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199608000-00002

    authors: Cree IA,Kurbacher CM,Untch M,Sutherland LA,Hunter EM,Subedi AM,James EA,Dewar JA,Preece PE,Andreotti PE,Bruckner HW

    更新日期:1996-08-01 00:00:00

  • Docetaxel and irinotecan (CPT-11) in the treatment of malignant pleural mesothelioma--a feasibility study.

    abstract::We chose to treat malignant pleural mesothelioma with a combination of docetaxel and irinotecan (CPT-11), because there have been preliminary reports that CPT-11 is active against mesothelioma, and docetaxel and CPT-11 were the most active agents in our in vitro experiments in human mesothelioma cell lines. Fifteen pr...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-200004000-00005

    authors: Knuuttila A,Ollikainen T,Halme M,Mali P,Kivisaari L,Linnainmaa K,Jekunen A,Mattson K

    更新日期:2000-04-01 00:00:00

  • Ex vivo effects of the dual topoisomerase inhibitor tafluposide (F 11782) on cells isolated from fresh tumor samples taken from patients with cancer.

    abstract::Tafluposide (F 11782), a novel epipodophylloid with a unique mechanism of interaction with both topoisomerase I and II, has shown outstanding antitumor activity in vivo against a panel of experimental human tumor xenografts. The aim of this study was to evaluate its cytotoxicity against fresh tumor cells taken from pa...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200307000-00013

    authors: Sargent JM,Elgie AW,Williamson CJ,Hill BT

    更新日期:2003-07-01 00:00:00

  • Methotrexate concentrations in cerebrospinal fluid and serum, and the risk of central nervous system relapse in children with acute lymphoblastic leukaemia.

    abstract::The aim of the study was to characterize the relationship between the pharmacokinetics of methotrexate in serum and concentrations in the cerebrospinal fluid, and to analyse the association to risk of a central nervous system relapse in children with acute lymphoblastic leukaemia. In this retrospective study, 353 chil...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3281430bd1

    authors: Jönsson P,Höglund P,Wiebe T,Schrøder H,Seidel H,Skärby T

    更新日期:2007-09-01 00:00:00

  • Clinical significance of a prostate-specific antigen flare phenomenon in patients with hormone-refractory prostate cancer receiving docetaxel.

    abstract::Docetaxel has shown promise for the treatment of hormone-refractory prostate cancer and has become the standard of care. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of hormone-refractory prostate cancer. Th...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000231468.69535.97

    authors: Olbert PJ,Hegele A,Kraeuter P,Heidenreich A,Hofmann R,Schrader AJ

    更新日期:2006-09-01 00:00:00

  • Generation of DNA damage by anti-neoplastic agents.

    abstract::DNA has been one of the major targets of cancer chemotherapy. A variety of anti-neoplastic agents can cause different types of DNA lesions, including base alterations, single- or double-strand DNA breaks, DNA-DNA cross-links and DNA-protein cross-links. The exact processes by which these DNA lesions lead to cell death...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/00001813-199112000-00003

    authors: Kubota M

    更新日期:1991-12-01 00:00:00

  • Inhibition of macromolecular synthesis by cryptophycin-52.

    abstract::Cryptophycin (CP)-52, a synthetic analog of CP-1, possesses potent and selective antiproliferative activity against human solid tumors both and. Based on an algorithm developed in this laboratory using HCT-116 human colon adenocarcinoma cells, CP-52 exhibited a time- and concentration-dependent antiproliferative effec...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200211000-00010

    authors: Subramanian B,Nakeff A,Media JE,Wiegand RA,Valeriote FA

    更新日期:2002-11-01 00:00:00

  • No pharmacokinetic drug-drug interaction between nevirapine and paclitaxel.

    abstract::We have investigated the pharmacokinetics of nevirapine and paclitaxel in a patient who used both drugs concomitantly, as there are strong theoretical indications for a potential pharmacokinetic drug-drug interaction. Plasma concentrations of nevirapine (dose: 200 mg twice daily orally) and paclitaxel (dose: 100 mg/m(...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200507000-00006

    authors: Kappelhoff BS,Huitema AD,Mairuhu AT,Schellens JH,Beijnen JH

    更新日期:2005-07-01 00:00:00

  • Cytotoxicity of cantharidin analogues targeting protein phosphatase 2A.

    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

    authors: Shan HB,Cai YC,Liu Y,Zeng WN,Chen HX,Fan BT,Liu XH,Xu ZL,Wang B,Xian LJ

    更新日期:2006-09-01 00:00:00

  • Inhibition of breast and ovarian carcinoma cell growth by 1,25-dihydroxyvitamin D3 combined with retinoic acid or dexamethasone.

    abstract::This study examined the growth inhibitory effects of combining 1,25-dihydroxyvitamin D3 (calcitriol) with retinoic acid or dexamethasone against cultured breast and ovarian carcinoma cells. Retinoic acid (12.5-50 nM) increased the effectiveness of calcitriol (12.5-50 nM) against MCF-7 and NIH:OVCAR3 cells, with synerg...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199508000-00009

    authors: Saunders DE,Christensen C,Williams JR,Wappler NL,Lawrence WD,Malone JM,Malviya VK,Deppe G

    更新日期:1995-08-01 00:00:00

  • Regulation of apoptosis-associated genes by histone deacetylase inhibitors: implications in cancer therapy.

    abstract::Anomalous gene regulation, dictated by epigenetic modifications, is a universal characteristic of cancer cells. Histone deacetylases (HDACs) are an important class of enzymes that influence gene expression by the removal of acetyl groups from histones leading to chromatin remodeling and transcriptional suppression of ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0b013e32833dad91

    authors: Jazirehi AR

    更新日期:2010-10-01 00:00:00

  • Evaluation of the antineoplastic activity of gallic acid in oral squamous cell carcinoma under hypoxic conditions.

    abstract::The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000342

    authors: Guimaraes TA,Farias LC,Fraga CA,Feltenberger JD,Melo GA,Coletta RD,Souza Santos SH,de Paula AM,Guimaraes AL

    更新日期:2016-06-01 00:00:00

  • Severe bladder contracture leading to cystectomy after intravesical mitoxantrone chemotherapy.

    abstract::Since the early 1990s, mitoxantrone has been used as a chemotherapeutic agent for adjuvant intravesical treatment following transurethral resection of superficial transitional cell carcinomas of the bladder. Although its efficacy as adjuvant intravesical therapy remains questionable and its use has not gained wide acc...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/cad.0b013e3282f421fe

    authors: Giannakopoulos S,Pantazis T,Kalaitzis C,Antoniou D,Patris E,Touloupidis S

    更新日期:2008-03-01 00:00:00

  • Combination effects of SC144 and cytotoxic anticancer agents.

    abstract::Previously, we synthesized a series of hydrazide class of compounds and examined their cytotoxicity in a number of cancer cell lines. Among these analogues, SC144 exhibited potent cytotoxicity against a panel of drug-sensitive and drug-resistant cancer cell lines. To further explore its therapeutic potentials in the c...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328323a7ca

    authors: Oshima T,Cao X,Grande F,Yamada R,Garofalo A,Louie S,Neamati N

    更新日期:2009-06-01 00:00:00

  • Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel-erlotinib and 5-fluoro-5'-deoxyuridine.

    abstract::The current reference treatment of hormone-refractory prostate cancer consists mainly of chemotherapy with docetaxel. To improve the management of advanced prostate cancer, one should examine the benefits of adding other agents to docetaxel. We examined the growth inhibitory effects of a triple combination, including ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000224444.23953.90

    authors: Fischel JL,Ciccolini J,Formento P,Ferrero JM,Milano G

    更新日期:2006-08-01 00:00:00

  • Silibinin affects tumor cell growth because of reduction of stemness properties and induction of apoptosis in 2D and 3D models of MDA-MB-468.

    abstract::Silibinin, with a strong antioxidant activity and a weak cytotoxic property, is considered a candidate for cancer prevention. As there is no information on its effect on breast cancer tumor-initiating cells [cancer stem cells (CSCs)] in a 3D culture model, which more closely mimic natural tissues, we carried out this ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000205

    authors: Abdollahi P,Ebrahimi M,Motamed N,Samani FS

    更新日期:2015-06-01 00:00:00

  • D-TRP-6-LHRH (Triptorelin) is not effective in ovarian carcinoma: an EORTC Gynaecological Cancer Co-operative Group Study.

    abstract::Between March and September 1988, 74 patients with progressive ovarian cancer after prior platinum-based therapy were treated with the luteinizing hormone-releasing hormone (LHRH) agonist Triptorelin (Decapeptyl degrees). Treatment consisted of i.m. injection of 3.75 mg of microencapsulated Triptorelin on days 1, 8 an...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1097/00001813-200102000-00010

    authors: Duffaud F,van der Burg ME,Namer M,Vergote I,Willemse PHB,ten Bokkel Huinink W,Guastalla JP,Nooij,Kerbrat P,Piccart M,Tumolo S,Favalli G,van der Vange N,Lacave AJ,Wils J,Splinter TA,Einhorn N,Roozendaal KJ,Rosso R,Ve

    更新日期:2001-02-01 00:00:00