Two repeated low doses of doxorubicin are more effective than a single high dose against tumors overexpressing P-glycoprotein.

Abstract:

:Standard chemotherapeutic protocols, based on maximum tolerated doses, do not prevent nor overcome chemoresistance caused by the efflux transporter P-glycoprotein (Pgp). We compared the effects of two consecutive low doses versus a single high dose of doxorubicin in drug-sensitive Pgp-negative and drug-resistant Pgp-positive human and murine cancer cells. Two consecutive low doses were significantly more cytotoxic in vitro and in vivo against drug-resistant tumors, while a single high dose failed to do so. The greater efficacy of two consecutive low doses of doxorubicin could be linked to increased levels of intracellular reactive oxygen species. These levels were produced by high electron flux from complex I to complex III of the mitochondrial respiratory chain, unrelated to the synthesis of ATP. This process induced mitochondrial oxidative damage, loss of mitochondrial potential and activation of the cytochrome c/caspase 9/caspase 3 pro-apoptotic axis in drug-resistant cells. Our work shows that the "apparent" ineffectiveness of doxorubicin against drug-resistant tumors overexpressing Pgp can be overcome by changing the timing of its administration and its doses.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Riganti C,Gazzano E,Gulino GR,Volante M,Ghigo D,Kopecka J

doi

10.1016/j.canlet.2015.02.008

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

219-26

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(15)00099-3

journal_volume

360

pub_type

杂志文章
  • Inhibition of tumour promotion in mouse skin by extracts of rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia), unique South African herbal teas.

    abstract::The modulating effect of ethanol/acetone (E/A) soluble fractions, prepared from methanolic extracts of processed and unprocessed rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) as well as green (Camellia sinensis) teas was established in a two-stage mouse skin carcinogenesis assay. Topical applicatio...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2004.11.014

    authors: Marnewick J,Joubert E,Joseph S,Swanevelder S,Swart P,Gelderblom W

    更新日期:2005-06-28 00:00:00

  • Metastasis of breast tumor cells to brain is suppressed by targeting RLIP alone and in combination with 2'-Hydroxyflavanone.

    abstract::Brain metastasis is an important cause of morbidity and mortality in cancer-patients. Breast tumor cells frequently metastasize to brain and initiate severe therapeutic complications. In the present study, we evaluated the anti-metastatic effects of 2'-hydroxyflavanone (2HF) alone and in combination with RLIP targeted...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2018.09.015

    authors: Singhal J,Singhal P,Horne D,Salgia R,Awasthi S,Singhal SS

    更新日期:2018-12-01 00:00:00

  • Reduction in NaCl-enhanced gastric carcinogenesis in rats fed a high-protein diet.

    abstract::The effect of a purified, high protein diet on enhanced gastric carcinogenesis induced by oral administration of NaCl was investigated in Wistar rats. Rats were fed on a purified diet with an equalized caloric content, containing 8% NaCl and 25% casein (normal protein diet), or 50% casein (high protein diet) after ora...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(97)00197-3

    authors: Tatsuta M,Iishi H,Baba M,Uehara H,Nakaizumi A,Iseki K

    更新日期:1997-06-24 00:00:00

  • The regulation of radiosensitivity by p53 and its acetylation.

    abstract::The p53 signaling pathway plays critical roles in determining the radio-sensitivity of normal tissues but is frequently inactivated in cancer. In various cancer cells, p53 has different effects on radio-sensitivity through complex mechanisms. Acetylation of p53 is an important means of post-translational modifications...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2015.04.015

    authors: Zhang J,Shen L,Sun LQ

    更新日期:2015-07-28 00:00:00

  • Carcinogen-induced alteration in liver epidermal growth factor receptor distribution during the promotion stage of hepatocarcinogenesis in rat.

    abstract::Changes in hepatic membrane binding capacity for epidermal growth factor (EGF) were assessed during 2-acetylaminofluorine (2-AAF)-induced hepatocarcinogenesis. An overall decrease in membrane EGF binding levels was observed throughout the period of 2-AAF administration. Immunochemical studies indicated the decreases i...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(96)04524-7

    authors: DeCicco LA,Kong J,Ringer DP

    更新日期:1997-01-01 00:00:00

  • An novel inhibitor of TGF-β type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition.

    abstract::TGF-β signaling plays an important role in breast cancer progression and metastasis. Epithelial-mesenchymal transition (EMT) is an important step in the progression of solid tumors to metastatic disease. We previously reported that IN-1130, a novel transforming growth factor-β type I receptor kinase (ALK5) inhibitor, ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2014.05.006

    authors: Park CY,Min KN,Son JY,Park SY,Nam JS,Kim DK,Sheen YY

    更新日期:2014-08-28 00:00:00

  • Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab.

    abstract::Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, w...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2016.09.020

    authors: Luo J,Hong Y,Lu Y,Qiu S,Chaganty BK,Zhang L,Wang X,Li Q,Fan Z

    更新日期:2017-01-01 00:00:00

  • Increased expression of cyclooxygenase-2 protein in rat lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine.

    abstract::Expression of cyclooxygenase (COX)-2 protein in preneoplastic and neoplastic lung lesions induced by the administration of 2000 ppm of N-nitrosobis(2-hydroxypropyl)amine (BHP) in the drinking water to Wistar male rats, was examined immunohistochemically. The majority of alveolar/bronchiolar adenomas (ADs) and all aden...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(99)00325-0

    authors: Kitayama W,Denda A,Yoshida J,Sasaki Y,Takahama M,Murakawa K,Tsujiuchi T,Tsutsumi M,Konishi Y

    更新日期:2000-02-01 00:00:00

  • Prevention of spontaneous and chemically induced carcinogenesis using activated carbon fiber adsorbent. III. Inhibitory effect of the activated carbon fiber adsorbent 'Aqualen' on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in rats.

    abstract::Two-month-old outbred female LIO rats were exposed weekly to 15 (experiment I, groups 1, 2 and 3) or to 5 (experiment II, groups 4, 5 and 6) subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg of body weight. From the day of the first injection of the carcinogen, the rats from groups 2,...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(98)00362-0

    authors: Anisimov VN,Zabezhinski MA,Popovich IG,Berstein LM,Kovalenko IG,Lieberman AI,Shmidt JL

    更新日期:1999-04-26 00:00:00

  • Dietary ortho phenols that induce glutathione S-transferase and increase the resistance of cells to hydrogen peroxide are potential cancer chemopreventives that act by two mechanisms: the alleviation of oxidative stress and the detoxification of mutagenic

    abstract::Oxidative stress is implicated in the etiology of cancer, hence compounds that alleviate oxidative stress by inducing enzymes that defend against free radical damage might be useful as cancer chemopreventives. Glutathione S-transferase (GST) has been suggested to be a candidate for a critical enzyme in protecting cell...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00368-2

    authors: Fiander H,Schneider H

    更新日期:2000-08-11 00:00:00

  • Anterior gradient 2: a novel player in tumor cell biology.

    abstract::AGR2 has evolutionarily conserved roles in development and tissue regeneration and is linked with several human cancers. The exact functions and regulation of AGR2 are poorly understood, but current data identify AGR2 as a clinically relevant factor that modulates the behavior and response of hormone-dependent cancers...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2010.12.023

    authors: Brychtova V,Vojtesek B,Hrstka R

    更新日期:2011-05-01 00:00:00

  • DNA fragmentation by 2-nitropropane in rat tissues, and effects of the modulation of biotransformation processes.

    abstract::The occurrence and persistence of DNA fragmentation, as detected by the alkaline elution technique, have been studied in rats treated with single oral doses of the hepatocarcinogen 2-nitropropane (2-NP). A progressive increase of liver DNA fragmentation was observed at doses ranging from 0.5 to 8 mmol/kg; single stran...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(91)90064-o

    authors: Robbiano L,Mattioli F,Brambilla G

    更新日期:1991-04-01 00:00:00

  • Microsatellite instability in Japanese hereditary non-polyposis colorectal cancer does not induce mutation of a simple repeat sequence of the bax gene.

    abstract::The identification of frameshift mutations in the coding region of the bax gene in Western cases of hereditary non-polyposis colorectal cancer provided evidence that the disease could be caused by the disruption of a tumor suppressor gene associated with microsatellite instability. In order to determine whether this o...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(97)00477-1

    authors: Sakakibara T,Nakamura T,Yamamoto M,Matsuo M

    更新日期:1998-02-27 00:00:00

  • MiRNA-29b suppresses tumor growth through simultaneously inhibiting angiogenesis and tumorigenesis by targeting Akt3.

    abstract::The traditional anti-angiogenic cancer therapy could trigger hypoxia induced factor (HIF) response, leading to "reactive resistance" to chemotherapy. Simultaneously inhibiting both angiogenesis and tumorigenesis would be ideal to overcome this limitation. MicroRNAs (miRNAs) are increasingly explored as new agents for ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2017.03.032

    authors: Li Y,Cai B,Shen L,Dong Y,Lu Q,Sun S,Liu S,Ma S,Ma PX,Chen J

    更新日期:2017-07-01 00:00:00

  • Up-regulated isocitrate dehydrogenase 1 suppresses proliferation, migration and invasion in osteosarcoma: in vitro and in vivo.

    abstract::Very few studies have been reported the function of wild type IDH1 in tumor progress. Previously, we reported that IDH1 correlated with pathological grade and metastatic potential inversely in human osteosarcoma. Here, IDH1 was found lower expressed in osteosarcoma tissues than that of adjacent normal bone tissues. In...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2013.12.020

    authors: Hu X,Liu Y,Qin C,Pan Z,Luo J,Yu A,Cheng Z

    更新日期:2014-04-28 00:00:00

  • An inverse correlation between hepatic ornithine decarboxylase and S-adenosylmethionine in rats.

    abstract::The comparative effects of the subchronic administration to rats of ethionine-supplemented and of chemically defined methyl-deficient diets on the hepatic levels of S-adenosylmethionine (SAM) and of ornithine decarboxylase (ODC), an enzyme marker of cell proliferation, were studied. Both treatments led to decreased he...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(81)90018-5

    authors: Mikol YB,Poirier LA

    更新日期:1981-08-01 00:00:00

  • Antibodies directed against L1-CAM synergize with Genistein in inhibiting growth and survival pathways in SKOV3ip human ovarian cancer cells.

    abstract::Antibodies directed against the L1 cell adhesion protein inhibit growth of SKOV3ip human ovarian cancer cells in vitro and in vivo. Responses of SKOV3ip cells in vitro to anti-L1 mAb chCE7 and Genistein were investigated. Genistein potentiated the anti-proliferative and pro-apoptotic effects of chCE7 in SKOV3ip cells....

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2007.11.012

    authors: Novak-Hofer I,Cohrs S,Grünberg J,Friedli A,Schlatter MC,Pfeifer M,Altevogt P,Schubiger PA

    更新日期:2008-03-18 00:00:00

  • Genistein potentiates the effect of arsenic trioxide against human hepatocellular carcinoma: role of Akt and nuclear factor-κB.

    abstract::Hepatocellular carcinoma (HCC) is a highly lethal malignancy mostly because of de novo and acquired resistance to conventional chemotherapy. Constitutive activation of Akt and nuclear factor-κB (NF-κB) represent major cellular abnormalities associated with both the pathogenesis and therapeutic resistance of HCC. The a...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2010.10.022

    authors: Ma Y,Wang J,Liu L,Zhu H,Chen X,Pan S,Sun X,Jiang H

    更新日期:2011-02-01 00:00:00

  • Decreased plasma levels of cholecystokinin in healthy males after chronic ingestion of a heat-treated soya product.

    abstract::Administration of raw soya containing a trypsin inhibitor stimulated excessive release of cholecystokinin (CCK) which led to pancreatic hypertrophy, hyperplasia and cancer in the rats (Booth et al. (1964) Proc. Soc. Exp. Biol. Med., 116, 1067). More postprandial CCK release in healthy humans was observed after ingesti...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(95)03697-u

    authors: Lu LJ,Anderson KE,Gomez G,Nealon WH

    更新日期:1995-04-14 00:00:00

  • Caveolins in the development and diseases of musculoskeletal system.

    abstract::Caveolins, essential scaffold proteins of caveolae, have emerged as versatile molecules that can influence numerous signaling pathways and disease processes. This brief review is focused on the role of caveolins in the physiology and pathology of musculoskeletal system and will discuss the key features of caveolins as...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2009.02.016

    authors: Serra M,Scotlandi K

    更新日期:2009-11-01 00:00:00

  • Cancer chemopreventive activity of flavanones on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

    abstract::To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of ten flavanones isolated from plants belonging to Rutaceae and Leguminosae by examining their possible inhibitory effects on Epstein-Barr virus (EBV) early antigen activation induced by 12-O-tetradecanoylphorbol...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(01)00740-6

    authors: Itoigawa M,Ito C,Ju-ichi M,Nobukuni T,Ichiishi E,Tokuda H,Nishino H,Furukawa H

    更新日期:2002-02-08 00:00:00

  • Anti-EGFR and ErbB-2 antibodies attenuate cyclooxygenase-2 expression and cooperatively inhibit survival of human colon cancer cells.

    abstract::Cyclooxygenase-2 (COX-2) is a transcriptional target and downstream effector of the ErbB-1 (EGFR) and ErbB-2 signaling pathways. We found that anti-EGFR and anti-ErbB-2 antibodies inhibited ERK phosphorylation and downregulated COX-2 protein expression in HCA-7 human colon carcinoma cells. Both antibodies also augment...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2006.11.020

    authors: Half E,Sun Y,Sinicrope FA

    更新日期:2007-06-28 00:00:00

  • The induction of sister chromatid exchanges by dihydrodiols derived from 7,12-dimethylbenz[a]anthracene and 3-methylcholanthrene.

    abstract::The in vitro induction of sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells by the polycyclic hydrocarbons, 7,12-dimethylbena[a]anthracene and 3-methylcholanthrene and some of the related dihydrodiols was investigated. Increased numbers of SCEs were seen in the chromosomes of cells exposed to non-...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(79)80075-0

    authors: Pal K,Grover PL,Sims P

    更新日期:1979-06-01 00:00:00

  • The PHGDH enigma: Do cancer cells only need serine or also a redox modulator?

    abstract::Upregulation of serine biosynthesis pathway activity is an increasingly apparent feature of many cancers. Most notably, the first rate-limiting enzyme of the pathway, phosphoglycerate dehydrogenase (PHGDH), is genomically amplified in some melanomas and breast cancers and can be transcriptionally regulated by various ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.01.036

    authors: Li AM,Ye J

    更新日期:2020-04-28 00:00:00

  • PET/CT imaging-guided dose painting in radiation therapy.

    abstract::Application of functional imaging to radiotherapy (RT) is a rapidly expanding field with the development of new modalities and techniques. Functional imaging of PET in conjunction with RT provides new avenues towards the clinical application of dose painting - a new RT strategy delivering optimized dose redistribution...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2014.07.042

    authors: Shi X,Meng X,Sun X,Xing L,Yu J

    更新日期:2014-12-28 00:00:00

  • Chromosomal mapping of human genes by radioactive hybridization of cDNAs to CEPH-YAC high density gridded filter sets.

    abstract::Chromosomal assignment of human transcribed sequences has been done mainly by high throughput genome analysis in specialized genome centres and, in a more classical fashion, by fluorescence in-situ hybridization (FISH) analysis. Not every laboratory has the ability to map cDNAs by FISH analysis. We here report a rapid...

    journal_title:Cancer letters

    pub_type: 更正并重新发布的文章,杂志文章

    doi:10.1016/s0304-3835(00)00690-x

    authors: Claas A,Savelyeva L,Pillmann A,Schwab M

    更新日期:2001-01-10 00:00:00

  • Distinct mechanisms for opposite functions of homeoproteins Cdx2 and HoxB7 in double-strand break DNA repair in colon cancer cells.

    abstract::Homeobox genes, involved in embryonic development and tissues homeostasis in adults, are often deregulated in cancer, but their relevance in pathology is far from being fully elucidated. In colon cancers, we report that the homeoproteins HoxB7 and Cdx2 exhibit different heterogeneous patterns, Cdx2 being localized in ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2016.02.026

    authors: Soret C,Martin E,Duluc I,Dantzer F,Vanier M,Gross I,Freund JN,Domon-Dell C

    更新日期:2016-05-01 00:00:00

  • Mutagenicity of chamuvaritin: a benzyldihydrochalcone isolated from a medicinal plant.

    abstract::The mutagenic effects of chamuvaritin, dihydrobenzylchalcone isolated from Uvaria chamae, were investigated using Salmonella typhimurium tester strains TA92, TA94--98, TA100--1535, TA1537 and TA1538. The phytochemical was mutagenic in tester strains TA98 and TA100 and required activation by the hepatic S-9 microsomal ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(79)90027-2

    authors: Uwaifo AO,Okorie DA,Bababunmi EA

    更新日期:1979-11-01 00:00:00

  • IC-4, a new irreversible EGFR inhibitor, exhibits prominent anti-tumor and anti-angiogenesis activities.

    abstract::Accumulating evidence suggested that the irreversible tyrosine kinase inhibitors (TKIs) have potential to override the acquired resistance to target-based therapies. Herein, we reported IC-4 as a novel irreversible TKI for epidermal growth factor receptor (EGFR). IC-4 potentially suppressed proliferation, induced apop...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2013.07.005

    authors: Li YB,Wang ZQ,Yan X,Chen MW,Bao JL,Wu GS,Ge ZM,Zhou DM,Wang YT,Li RT

    更新日期:2013-10-28 00:00:00

  • Growth suppression and apoptosis induction in synovial sarcoma cell lines by a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ).

    abstract::Synovial sarcoma is a relatively common soft tissue sarcoma with an aggressive clinical course. Although surgery is currently the first treatment modality, improvement of adjuvant chemotherapy is deemed essential to improve the clinical outcome. Nuclear factor-kappaB (NF-kappaB) is constitutively activated in various ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2008.07.021

    authors: Horiuchi K,Morioka H,Nishimoto K,Suzuki Y,Susa M,Nakayama R,Kawai A,Sonobe H,Takaishi H,Ozaki T,Yabe H,Umezawa K,Toyama Y

    更新日期:2008-12-18 00:00:00