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Aristolochia sp. plants are used in traditional medicine because of their immunostimulatory and anticarcinogenic properties, despite their content of aristolochic acids (AAs), carcinogenic and nephrotoxic agents. Therefore, ethanolic extracts of Aristolochia clematitis leaves, a specie growing in Western Romania, were obtained to study antioxidant and cytotoxic effects. The antioxidant capacity of the extract was evaluated by five in vitro chemical-based assays, proving that ABTS assay was a better method for this type of evaluation showing an IC50 of 160.89 ± 0.21 µg/mL. Furthermore, the cytotoxic effects of the extract were established by an IC50 of 216 µg/mL for 24 h by MTT assay, followed by a cell-based assay on Caco-2 cells by the ABTS method. The antioxidant effects of the A. clematitis extract demonstrate potential therapeutic applications in complementary medicine. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of study’s goal was to look into the anticancer efficacy of a methanolic extract of Justicia gendarussa against a lung cancer cell line. Materials and MethodsCell viability assays and cell and nuclear morphology examinations were used to evaluate the anticancer efficacy against methanolic extract of Justicia gendarussa on lung cancer cell lines. The IC50 doses were calculated using different concentrations of Justicia gendarussa extract (0, 10, 20, 40, 60, and 80 μg/mL). ResultsThe results of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay revealed that the percentage of viability in treated cells was significantly lower as compared with untreated control groups, which represented as 100%, and an inhibitory concentration of 40 μg/mL was observed. Under a phase-contrast microscope, morphological changes revealed cell shrinkage and cytoplasmic membrane blebbing. The apoptotic nuclei (intensely colored, broken nuclei, and compacted chromatin) were examined under a fluorescence microscope. ConclusionsThe outcome of the research work on Justicia gendarussa was investigated for anticancer properties. The results revealed the proapoptotic and cytotoxic effects of Justicia gendarussa extract on lung cancer cell lines. From the above results and findings, it could be concluded that the Justicia gendarussa methanolic leaf extract exhibited potent anticancer activity against a lung cancer cell line. Further study needs to be conducted to investigate the active chemicals in the extract as well as the molecular mechanisms underlying its anticancer benefits.

BackgroundCancer rates continue to climb, owing largely to the world population’s aging and growth, as well as economically developing countries, a surge in cancer-causing behavior, particularly smoking. The third or fourth most prevalent type of cancer is colon cancer. Cancer of the large intestine (colon) is one of the primary causes of death from cancer. Colorectal cancer prevention is mostly based on adenomatous disease screening approaches. The cytotoxic and pharmacological properties of Phoenix pusilla are widely documented. As a result, there is little recorded evidence of its cytotoxic activity against colon cancer cells. Therefore, we planned to study the efficacy of a methanolic leaf extract of Phoenix pusilla against in vitro colon cancer cells. AimTo evaluate the anti-cancer effects of the methanolic leaf extract of Phoenix pusilla on colon cancer cell lines. Materials and MethodsIn vitro screening and anti-cancer effects of the methanolic effect of Phoenix pusilla on colon cancer cell lines were assessed by cell viability assays and cell and nuclear morphological studies. For the in vitro cell culture study, different concentrations of Phoenix pusilla leaf extract (0, 25, 50, 75, 100, 150 μg/ml) were used, and IC50 doses were calculated. ResultsThe results of the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay revealed that the fraction of viability cells significantly decreased in treated cells when compared to untreated control groups, was expressed as 100%, and an inhibitory concentration of μg/ml was identified. A phase-contrast microscope was used to observe cell shrinkage and cytoplasmic membrane blebbing. A fluorescent microscope was used to examine the apoptotic nuclei (internally dyed nuclei, shattered nuclei, and condensed chromatin). ConclusionIn conclusion, the present study results showed that the leaf extracts of Phoenix pusilla had a strong cytotoxic effect and induced significant apoptosis in the colon cancer cell lines at a concentration of 75 μg/ml in the 24 h incubation period. More research is needed to investigate the extract’s active components as well as the molecular mechanisms underlying its anti-cancer properties.

Aristolochia sp. plants are used in traditional medicine because of their immunostimulatory and anticarcinogenic properties, despite their content of aristolochic acids (AAs), carcinogenic and nephrotoxic agents. Therefore, ethanolic extracts of Aristolochia clematitis leaves, a specie growing in Western Romania, were obtained to study antioxidant and cytotoxic effects. The antioxidant capacity of the extract was evaluated by five in vitro chemical-based assays, proving that ABTS assay was a better method for this type of evaluation showing an IC50 of 160.89 ± 0.21 µg/mL. Furthermore, the cytotoxic effects of the extract were established by an IC50 of 216 µg/mL for 24 h by MTT assay, followed by a cell-based assay on Caco-2 cells by the ABTS method. The antioxidant effects of the A. clematitis extract demonstrate potential therapeutic applications in complementary medicine.

The root extract of Eurycoma longifolia Jack has been shown to be effective against different type of cancers. Present study was carried out to study the effect of three biotic elicitors, yeast extract, pectin, and valine, on the cytotoxicity activity of the bioactive compounds produced in the cell suspension culture of E. longifolia against human colon cancer cell lines. Yeast extract consists of vitamin B complex, chitin, N-acetyl-glucosamin, β-glucan, glycopeptide, and ergosterol, while pectin contains cell wall components. Yeast extract and pectin, along with the branched chain amino acid valine, were evaluated as biotic elicitors to trigger the production of plant defense–related compounds. The different stages of cell growth influenced the production of the bioactive compounds; hence the administration of the elicitors at different stage of cell growth is vital for enhancement of their production. The results showed that all three biotic elicitors were effective in enhancing cytotoxic activity similar to that of root extract from the mature plant against human colon cancer cell line, HCT116, without affecting its cell growth. Crude extract derived from cells elicited with 2.0 g L−1 pectin supplemented on the 17th d showed good inhibition of HCT116 cell proliferation with IC50 of 19.4 μg mL−1. Hence, cell suspension culture of E. longifolia with elicitation is an alternative time-saving tool for production of valuable anti-cancer compounds and the conservation of this valuable plant due to indiscriminate harvesting from its natural habitat. [ABSTRACT FROM AUTHOR]

UnlabelledVascular endothelial growth factor A (referred to as VEGF) is implicated in colon cancer growth. Currently, the main accepted mechanism by which VEGF promotes colon cancer growth is via the stimulation of angiogenesis, which was originally postulated by late Judah Folkman. However, the cellular source of VEGF in colon cancer tissue; and, the expression of VEGF and its receptors VEGF-R1 and VEGF-R2 in colon cancer cells are not fully known and are subjects of controversy.Material and methodsWe examined and quantified expression of VEGF, VEGF-R1 and VEGF-R2 in three different human colonic tissue arrays containing sections of adenocarcinoma (n=43) and normal mucosa (n = 41). In human colon cancer cell lines HCT116 and HT29 and normal colon cell lines NCM356 and NCM460, we examined expression of VEGF, VEGF-R1 and VEGF-R2 mRNA and protein, VEGF production and secretion into the culture medium; and, the effect of a potent, selective inhibitor of VEGF receptors, AL-993, on cell proliferation.ResultsHuman colorectal cancer specimens had strong expression of VEGF in cancer cells and also expressed VEGF-R1 and VEGF-R2.In vitro studies showed that human colon cancer cell lines, HCT116 and HT29, but not normal colonic cell lines, express VEGF, VEGF-R1 and VEGF-R2 and secrete VEGF into the medium up to a concentration 2000 pg/ml within 48 h. Furthermore, we showed that inhibition of VEGF receptors using a specific VEGF-R inhibitor significantly reduced proliferation (by >50%) of cultured colon cancer cell lines.ConclusionsOur findings support the contention that VEGF generated by colon cancer cells stimulates their growth directly through an autocrine mechanism that is independent of its primary function in the induction of angiogenesis.

Background and Objectives: Till now, cancer is a major health problem and one of the main causes of mortality worldwide. Ascorbic acid and selenium are the two most popular dietary supplements used to prevent cancer proliferative, therefore, the work aims to study the antitumor effect of ascorbic acid and selenium on HCT116 and MCF7 cell lines.Materials and Methods: In the present study, the cytotoxic effect of different concentrations of ascorbic acid and selenium on human breast cancer cell line (MCF7 cells) and human colon carcinoma (HCT116) was studied.Results: Viability % of HCT116 cell line and MCF7 cell line decreased with increasing ascorbic acid concentrations (1-4 mM). The 50% inhibitory concentration (IC50) of five dilutions of each concentration of ascorbic acid was evaluated in the current study. IC50 was 0.18, 0.17, 0.16, and 0.16 mM for HCT116 cell line and was 0.86, 1.34, 1.74, and 0.47 mM for MCF7 cell line at 1, 2, 3, and 4 mM, respectively. Cell viability decreased depending on the selenium concentrations ranging from 20 to 100 mM. Selenium effect showed less cytotoxicity on MCF7 compared to HCT116 cells at all tested concentrations where the cell viability at 20, 40, 60, 80, and 100 mM selenium was 33.74, 29.48, 26.08, 54.53, and 20.89 for HCT116 cell and was 79.53, 76.01, 59.42, 54.53, and 51.98 for MCF7 cell, respectively. Ascorbic acid induced apoptosis by promoting the release of lactate dehydrogenase (LDH) in HCT116 and MCF7 cells, but reduced release of LDH was observed in selenium treatment but increased when it added to ascorbic acid because of a possible synergistic action that may produce an enhanced anticarcinogenic effect.Conclusion: The present study documented that a combination of ascorbic acid and selenium produces an additive chemopreventive effect on carcinogenesis. [ABSTRACT FROM AUTHOR]

Phenolic compounds are very important in the prevention and treatment of many civilization diseases, including colorectal cancer (CRC). In the present study we investigated and compared the phytochemical composition, antioxidant and cytotoxic activity of Japanese quince (Chaenomeles japonica L.) leaves crude phenolic extract (CPE) and purified phenolic-rich extracts (PRE). The UPLC-Q-TOF-MS analysis showed that both extracts contain diversified phenolics compounds (33 -- 36 compounds in the PRE and CPE, respectively), among which chlorogenic acid and naringenin hexoside turned out to be the main constituents. Both FRAP and ABTS tests showed that PRE had 2-fold higher antioxidant activity compared to CPE. Furthermore, PRE exhibited a higher cytotoxic activity towards colon cancer cells (SW-480 and HT-29) than CPE. After 24-hours incubation with PRE the IC50 value for SW-480 cell line was obtained at the concentration of 239 µg/mL, while CPE treatment caused the same decrease only after 72h at 277 µg/mL. In addition, PRE had a stronger cytotoxic effect on the colon cancer cell lines (SW-480 and HT-29) than on normal intestinal cells (CCD-18Co and CCD 841 CoN). These results provide the first evidence that extracts from Japanese quince leaves (especially phenolic-rich extract, PRE) strongly decrease the viability of both SW-480 and HT-29 lines, which may suggest their cytotoxic activity towards colon cancer cells. [ABSTRACT FROM AUTHOR]

Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells.

Colon cancer is among the most common and lethal cancer types worldwide. The disease is very heterogeneous and is attributed to the accumulation of genetic and epigenetic alterations affecting specific genes involved in the regulation of cell growth, proliferation, adhesion, and survival. About 20% of patients with colon cancer are diagnosed with distant metastases which is associated with worse prognosis and survival. The search for novel natural therapeutic agents with higher effectiveness against the diseases, and milder side effects is of great interest in oncopharmacology. Medicinal plants represents valuable source of biologically active compounds with a wide range of pharmacological activities. Our previous study detected antiproliferative properties of fustin isolated from the heartwood of Cotinus coggygria Scop. against the highly metastatic colon cancer cell line Colon 26 [1]. The aim of the present work was to investigate some of the molecular mechanisms underlying the anticancer properties of fustin in colon cancer cells. For this purpose, we applied clonogenic assay to evaluate single cell capability to form a colony, fluorescence microscopy analysis after staining with Annexin V/propidium iodide to assess the proapoptotic properties of the flavonoid, wound healing assay to study antimigratory potential of fustin and quantitative reverse transcription-polymerase chain reaction analysis of the relative expression levels of genes associated with the cell cycle control, programmed cell death, and metastasis. The obtained results revealed that fustin significantly suppressed the colony-forming potential of Colon 26 cells after treatment for a period of 7 days, induced early and late apoptotic events in cancer cells and considerably inhibited cellular migratory properties, with a statistically significant decrease in cell motility compared to the untreated control observed at the 72nd hour of treatment. Transcriptional analysis of gene expression supplied information on some molecular pathways of the anticancer action of fustin and provided directions for future more detailed research. [ABSTRACT FROM AUTHOR]

The Mediterranean-style diet is rich in fruit and vegetables and has a great impact on the prevention of major chronic diseases, such as cardiovascular diseases and cancer. In this work we investigated the ability of spinach extracts obtained by different extraction methods and of the single main components of the phytocomplex, alone or mixed, to modulate proliferation, antioxidant defense, and genotoxicity of HT29 human colorectal cells. Spinach extracts show dose-dependent activity, increasing the level of intracellular endogenous reactive oxygen species (ROS) when tested at higher doses. In the presence of oxidative stress, the activity is related to the oxidizing agent involved (H2O2 or menadione) and by the extraction method. The single components of the phytocomplex, alone or mixed, do not alter the intracellular endogenous level of ROS but again, in the presence of an oxidative insult, the modulation of antioxidant defense depends on the oxidizing agent used. The application of the phytocomplex extracts seem to be more effective than the application of the single phytocomplex components.

Abstract Silver nanoparticles (AgNPs) are being commercialized in a number of consumer products including food and cosmetics where there is a direct exposure of AgNPs to human body. An extensive toxicological evaluation is necessary to understand the mechanism for its safe use, since the toxicity effect varies greatly with the synthesis protocol followed. In this study, we report the detailed toxicological analysis of AgNPs fabricated by thermal co-reduction approach. Our study was analysed in human colon cancer cell line (HCT 116) and the IC 50 was calculated as 28.11 μg/ml. It was also observed that AgNP induces oxidative stress on HCT116 by increased levels of lipid peroxidation and reduced levels of glutathione. Mitochondrial membrane depolarization was also analysed and Western blot analysis confirms the increased level of Bcl and Caspase-3 which indicates the mitochondrial -mediated apoptosis. Additionally, flow cytometric analysis suggests cell cycle arrest in G2/M phase. Thus, our study can be a basis for further research to design safe AgNPs in various consumer products. Additionally, similar research can be conducted for different size and shape of AgNP or nano-silver can be engineered using different approaches. Graphical abstract Image 1 Highlights • Silver nanoparticles synthesized from thermal co-reduction approach. • Oxidative stress and Mitochondrial membrane depolarization. • Reactive oxygen species generation. • Western blot confirms Bcl-2 and Caspase-3 involvement. • Cell cycle arrest at G2/M phase. [ABSTRACT FROM AUTHOR]

This study aim to synthesize silver nanoparticles (AgNPs) usingAnthemis atropatanaextract and to evaluate their chemical characteristics and antimicrobial and cytotoxic effects. The biosynthesis of AgNPs is verified using UV–visible spectrum which showing maximum absorption in 430 nm wavelength. Transmission electron microscope (TEM) and scanning electron microscope (SEM) results revealed that AgNPs has a spherical shape with an average size of 38.89 nanometres. The crystalline structure of green synthesized AgNPs in optimal conditions was confirmed by XRD analysis. The pattern of XRD peaks related to face-centred cubic (fcc) (111), (200), (220), (311) and (222) observed. Also, FTIR results verified the AgNPs synthesis using plant extract. In biological tests, the MTT results indicate the dose dependence of cytotoxic effects of AgNPs on colon cancer cell lines (HT29). The AgNPs had maximum cytotoxicity on HT29 cancer cell line at 100 μg/ml concentration, which were statistically significant comparing control cells (p < .001). Moreover, real time PCR and flow cytometry results confirmed the apoptotic effects of AgNPs. According to the results, it seems that the green synthesis of AgNPs is an eco-friendly and cost effective approach. This research provides insight into the development of new anticancer and antibacterial agents. [ABSTRACT FROM AUTHOR]

This Letter deals with new non-natural diisothiocyanates, their mercapturic acid derivatives—conjugated with N -acetylcysteine as well as their antiproliferative activity towards human colon cancer cell lines and their inhibitory potency towards histone deacetylase activity. The activity of analysed isothiocyanates is not significantly different than their N -acetylcysteine conjugates. In comparison to simple mono-isothiocyanate analogues, aliphatic diisothiocyanates and their conjugates are much more active than the simple presence of two isothiocyanate functionalities could indicate. [ABSTRACT FROM AUTHOR]

Besides other mechanism(s) 17β-estradiol (E2) facilitates neuronal survival by increasing, via estrogen receptor β (ERβ), the levels of neuroglobin (NGB) an anti-apoptotic protein. In contrast, E2 could exert protective effects in cancer cells by activating apoptosis when the ERβ level prevails on that of ERα as in colon cancer cell lines. These apparently contrasting results raise the possibility that E2-induced NGB up-regulation could regulate the ERβ activities shunning this receptor subtype to trigger an apoptotic cascade in neurons but not in non-neuronal cells. Here, human colorectal adenocarcinoma cell line (DLD-1) that only expresses ERβ and HeLa cells transiently transfected with ERβ encoding vector has been used to verify this hypothesis. In addition, neuroblastoma SK-N-BE cells were used as positive control. Surprisingly, E2 also induced NGB up-regulation, in a dose- and time-dependent manner, in DLD-1 cells. The ERβ-mediated activation of p38/MAPK was necessary for this E2 effect. E2 induced NGB re-allocation in mitochondria where, subsequently to an oxidative stress injury (i.e., 100 μM H 2 O 2 ), NGB interacted with cytochrome c preventing its release into the cytosol and the activation of an apoptotic cascade. As a whole, these results demonstrate that E2-induced NGB up-regulation could act as an oxidative stress sensor, which does not oppose to the pro-apoptotic E2 effect in ERβ-containing colon cancer cells unless a rise of oxidative stress occurs. These results support the concept that oxidative stress plays a critical role in E2-induced carcinogenesis and further open an important scenario to develop novel therapeutic strategies that target NGB against E2-related cancers. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a prototype of endocrine disruptors, mimics 17β-estradiol (E2)-induced proliferation in several cancer cells by binding to estrogen receptor α (ERα). However, scarce and conflicting data are available concerning the effect of BPA on estrogen receptor β (ERβ)-mediated functions. Here, the detailed analysis of the effect of BPA, alone or in combination with E2, on ERβ-mediated cellular functions is reported in ERβ-expressing colon cancer cell line. BPA binds to ERβ without activating any receptor activities. On the other hand, BPA inhibits E2-induced genomic activity of ERβ as well as ERβ extra-nuclear activities (i.e., ERβ:p38 association and p38 activation). As a consequence, BPA impairs the E2-induced activation of the apoptotic cascade which is at the root of the protective role played by the hormone against colon cancer growth. Thus, women may be considered a highly susceptible population with an increased risk of colon cancers after BPA exposures. © 2010 IUBMB IUBMB Life, 62(9): 684-687, 2010 [ABSTRACT FROM AUTHOR]

Abstract: Introduction: We examined 3-[123I]iodo-α-methyl-l-tyrosine ([123I]IMT) uptake and inhibition by amino acids and amino acid-like drugs in the human DLD-1 colon cancer cell line, to discuss correlation between the inhibition effect and structure. Methods: Expression of relevant neutral amino acid transporters was examined by real-time PCR with DLD-1 cells. The time course of [125I]IMT uptake, contributions of transport systems, concentration dependence and inhibition effects by amino acids and amino acid-like drugs (1 mM) on [125I]IMT uptake were examined. Results: Expression of system L (4F2hc, LAT1 and LAT2), system A (ATA1, ATA2) and system ASC (ASCT1) was strongly detected; system L (LAT3, LAT4) and MCT8 were weakly detected; and B0AT was not detected. [125I]IMT uptake in DLD-1 cells involved Na+-independent system L primarily and Na+-dependent system(s). Uptake of [125I]IMT in Na+-free buffer followed Michaelis–Menten kinetics, with a K m of 78 μM and V max of 333 pmol/106 cells per minute. Neutral d- and l-amino acids with branched or aromatic large side chains inhibited [125I]IMT uptake. Tyrosine analogues, tryptophan analogues, l-phenylalanine and p-halogeno-l-phenylalanines, and gamma amino acids [including 3,4-dihydroxy-l-phenylalanine (l-DOPA), dl-threo-β-(3,4-dihydroxyphenyl)serine (DOPS), 4-[bis(2-chloroethyl)amino]-l-phenylalanine and 1-(aminomethyl)-cyclohexaneacetic acid] strongly inhibited [125I]IMT uptake, but l-tyrosine methyl ester and R(+)/S(−)-baclofen weakly inhibited uptake. The substrates of system ASC and A did not inhibit [125I]IMT uptake except l-serine and d/l-cysteine. Conclusions: [125I]IMT uptake in DLD-1 cells involves mostly LAT1 and its substrates'' (including amino acid-like drugs derived from tyrosine, tryptophan and phenylalanine) affinity to transport via LAT1. Whether transport of gamma amino acid analogues is involved in LAT1 depends on the structure of the group corresponding to the amino acid residue. Beta-hydroxylation may confer reduction of transport affinity of tyrosine analogues via LAT1. [Copyright &y& Elsevier]

Although genetic factors are a well-known cause of colorectal cancer, environmental factors contribute more to its development. Despite advances in the fields of surgery, radiotherapy and chemotherapy, the cure rates for colon cancer have not substantially improved over the past few decades. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the principal pungent ingredient of hot chili pepper, has exhibited an anti-tumor effect in many cell types. However, the mechanisms responsible for the anti-tumor effect of capsaicin are not yet completely understood. In this study, we investigated whether capsaicin induces apoptosis in colon cancer cell lines. Capsaicin decreased cell viability in a dose-dependent manner in Colo320DM and LoVo cells. In addition, capsaicin produced cell morphology changes and DNA fragmentation, decreased the DNA contents, and induced phosphatidylserine translocation, which is a hallmark of apoptotic cell death. We showed that capsaicin-induced apoptosis is associated with an increase in ROS generation and a disruption of the mitochondrial transmenbrane potential. A possible mechanism of capsaicin-induced apoptosis is the activation of caspase 3, a major apoptosis-executing enzyme. Treatment with capsaicin induced a dramatic increase in caspase 3 activity, as assessed by the cleavage of Ac-DEVD-AMC, a fluorogenic substrate. In conclusion, our results clearly showed that capsaicin induced apoptosis in colon cancer cells. Although the actual mechanisms of capsaicin-induced apoptosis remain uncertain, it may be a beneficial agent for colon cancer treatment and chemoprevention. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In order to improve tumor imaging, changes in the pharmacokinetics of 3-[12 3I]iodo-α-methyl-l-tyrosine ([12 3I]IMT), an artificial amino acid that exhibits high tumor accumulation, after probenecid (PBC) loading was studied in mice implanted with colon cancer DLD-1 cells using 12 5I-labeled IMT ([12 5I]IMT). Methods: DLD-1-implanted KSN-slc nude male mice received 740 kBq of [12 5I]IMT via the tail vein at 5 min after 50 mg/kg body weight PBC loading, and autoradiography was performed at 5, 15 and 30 min after injection. Male ddY mice then received 670 kBq of [12 5I]IMT and 50 mg/kg 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH) or p-aminohippurate (PAH) via the tail vein, and kidney autoradiography was performed at 5 min after injection. In vitro inhibition study was then performed based on the accumulation mechanisms of [12 5I]IMT in DLD-1, using 1 mM l-tyrosine, BCH, α-(methylamino)-isobutyric acid, N-benzoyl-β-alanine, PBC, PAH, 2,4-dinitrophenol and sodium azide. Both Na+-dependent and Na+-independent uptake were investigated. Results: Higher tumor accumulation in PBC-loaded DLD-1-implanted mice was seen when compared to control mice. PAH and BCH, respectively, reduced renal accumulation in the tubule segment-2 (S2)-like and S1-like regions. We confirmed that [12 5I]IMT transport is predominantly mediated by l-type amino acid transporter-1 in DLD-1 cells. Conclusions: [12 5I]IMT uptake is mediated by organic anion and amino acid transporters in the kidney. Organic anion transporter inhibitors may yield better tumor images with good tumor/normal tissue radioactivity ratios if adequate administration plans are developed. [Copyright &y& Elsevier]