The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Acriflavine enhances the antitumor activity of the chemotherapeutic drug 5‑fluorouracil in colorectal cancer cells
Open accessAbstract
5‑Fluorouracil (5‑FU)‑based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5‑FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5‑FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5‑FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay. SW480 cells that express a mutated form of p53 and two other CRC cell lines were used, HCT116 and LS174T, with wild‑type p53. To determine the effect of ACF on the sensitivity of cells to 5‑FU, cells were co‑treated with the 30% maximal inhibitory concentration (IC30) of ACF and various concentrations of 5‑FU, or pretreated with the IC30 of ACF and various concentrations of 5‑FU. To assess the mechanism of action of ACF, cells were treated with IC30 values of the compound and then the reverse transcription‑quantitative polymerase chain reaction was used to evaluate mRNA levels of hypoxia‑inducible factor‑1α (HIF‑1α) and topoisomerase 2. Results indicate that pretreatment with ACF markedly sensitized CRC cells to the cytotoxic effects of 5‑FU, whereas simultaneous treatment with ACF and 5‑FU were not able to alter the resistance of CRC cells to 5‑FU. In comparison with irinotecan, ACF was a more potent agent for enhancing the antitumor activity of 5‑FU. ACF did not alter the mRNA levels of either HIF‑1α or topoisomerase 2. The results of the present study reveal for the first time that pretreatment of CRC cells with ACF markedly increases the cytotoxic effects of 5‑FU, regardless of the p53 status of cells.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HIF-1 inhibitors have been shown to enhance the sensitivity of CRC cells to the cytotoxic effects of chemotherapy drugs like 5-FU and oxaliplatin.
“HIF-1 inhibitors have been shown to enhance the sensitivity of CRC cells to the cytotoxic effects of chemotherapy drugs like 5-FU and oxaliplatin [212,213,214].”
From Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer (2025) · cites this paper as [213]
Citations
Cites
2 retracted
RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
Lee, K., Zhang, H., Qian, D. Z., Rey, S., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909353106 · Cited by 451
RetractedSui, X., Kong, N., Wang, X., Fang, Y., Hu, X., Xu, Y., Chen, W., Wang, K., Li, D., Jin, W., et al. (2014) · Scientific Reports · doi:10.1038/srep04694 · Cited by 96
RetractedAnalysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012
Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., & Bray, F. (2015) · International Journal of Cancer · doi:10.1002/ijc.29210 · Cited by 28,766
Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer
Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Baron, A., Griffing, S., Holmgren, E., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032691 · Cited by 10,968
5-Fluorouracil: mechanisms of action and clinical strategies
Longley, D. B., Harkin, D. P., & Johnston, P. G. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1074 · Cited by 5,332
Siegel, R. L., Ward, E., Brawley, O. W., & Jemal, A. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20121 · Cited by 4,075
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
de Gramont, A., Figer, A., Seymour, M., Homerin, M., Hmissi, A., Cassidy, J., Boni, C., Cortes-Funes, H., Cervantes, A., Freyer, G., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.16.2938 · Cited by 3,815
Disruption of p53 in human cancer cells alters the responses to therapeutic agents.
Bunz, F., Hwang, P. M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6863 · Cited by 1,044
Peeters, M., Price, T. J., Cervantes, A., Sobrero, A. F., Ducreux, M., Hotko, Y., André, T., Chan, E., Lordick, F., Punt, C. J. A., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.6055 · Cited by 1,005
p53 mutations in colorectal cancer.
Rodrigues, N. R., Rowan, A., Smith, M. E., Kerr, I. B., Bodmer, W. F., Gannon, J., & Lane, D. P. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.19.7555 · Cited by 1,002
Tanoue, L. T. (2012) · Yearbook of Pulmonary Disease · doi:10.1016/j.ypdi.2012.01.043 · Cited by 479
Acridine--a neglected antibacterial chromophore
WAINWRIGHT, M. S. (2001) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/47.1.1 · Cited by 374
Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer
Coppedè, F. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i4.943 · Cited by 264
Cao, C. Q., Yan, T. D., Black, D. A., & Morris, D. L. (2009) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0487-4 · Cited by 251
Advanced colorectal cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up
Cutsem, E. V., & Oliveira, J. (2009) · Annals of Oncology · doi:10.1093/annonc/mdp130 · Cited by 202
Drug resistance, predictive markers and pharmacogenomics in colorectal cancer
Longley, D. B., Allen, W. L., & Johnston, P. G. (2006) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2006.08.001 · Cited by 173
Kuwai, T., Kitadai, Y., Tanaka, S., Onogawa, S., Matsutani, N., Kaio, E., Ito, M., & Chayama, K. (2003) · International Journal of Cancer · doi:10.1002/ijc.11068 · Cited by 162
Longley, D. B., Boyer, J. D., Allen, W. L., Latif, T., Ferguson, P., Maxwell, P. J., McDermott, U., Lynch, M., Harkin, D. P., & Johnston, P. G. (2002) · PubMed · Cited by 100
Aminoacridines, potent inhibitors of protein kinase C.
Hannun, Y. A., & Bell, R. M. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)60688-x · Cited by 99
Shay, J. E. S., Imtiyaz, H. Z., Sivanand, S., Durham, A. C., Skuli, N., Hsu, S., Mucaj, V., Eisinger‐Mathason, T. S. K., Krock, B. L., Giannoukos, D. N., et al. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu004 · Cited by 73
Role of targeted agents in metastatic colorectal cancer
Prenen, H., Vecchione, L., & Cutsem, E. V. (2013) · Targeted Oncology · doi:10.1007/s11523-013-0281-x · Cited by 70
The molecular therapy of colorectal cancer
Waldner, M. J., & Neurath, M. F. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.02.005 · Cited by 67
Weijer, R., Broekgaarden, M., Krekorian, M., Alles, L. K., van Wijk, A. C., Mackaaij, C., Verheij, J., van der Wal, A. C., van Gulik, T. M., Storm, G., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.6490 · Cited by 67
Novel activity of acriflavine against colorectal cancer tumor cells
Hassan, S. B., Laryea, D., Mahteme, H., Felth, J., Fryknäs, M., Fayad, W., Linder, S. T., Rickardson, L., Gullbo, J., Graf, W., et al. (2011) · Cancer Science · doi:10.1111/j.1349-7006.2011.02097.x · Cited by 61
Pereira, D. M., Simões, A. E. S., Gomes, S. E., Castro, R. E., Carvalho, T., Rodrigues, C. M. P., & Borralho, P. M. (2016) · Oncotarget · doi:10.18632/oncotarget.9107 · Cited by 56
Wang, H., Nan, L., Yu, D. S., Lindsey, J. R., Agrawal, S., & Zhang, R. (2002) · Molecular Medicine · doi:10.1007/bf03402011 · Cited by 50
Seth, P. K., Katayose, D., Li, Z., Kim, M., Wersto, R. P., Craig, C., Shanmugam, N., Ohri, E., Mudahar, B., Rakkar, A. N. S., et al. (1997) · PubMed · Cited by 41
Yin, T., He, S., Shen, G., & Wang, Y. (2015) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504014x13983417587366 · Cited by 35
Advanced colorectal cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up
Cutsem, E. V., & Oliveira, J. S. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn079 · Cited by 34
Enhanced Anti-tumour Effects of Acriflavine in Combination with Guanosine in Mice
Kim, S. G., Kim, C. W., Ahn, E.-T., Lee, K.-Y., Hong, E.-K., Yoo, B., & Han, Y.-B. (1997) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1997.tb06783.x · Cited by 31
Lim, M., Ahn, J., Han, Y., Yu, C., Kim, M., Lee, S., Lim, D., & Song, J. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.04.022 · Cited by 26
Mathé, G., Pontiggia, P., Orbach-Arbouys, S., Triana, K., Ambetima, N., Morette, C., Hallard, M., & Blanquet, D. (1996) · Biomedicine & Pharmacotherapy · doi:10.1016/0753-3322(96)87662-1 · Cited by 24
Chemotherapy for operable and advanced colorectal cancer
Aschele, C., Bergamo, F., & Lonardi, S. (2009) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2009.04.003 · Cited by 21
Antitumor activity of acriflavine in human hepatocellular carcinoma cells.
Lee, C. J., Yue, C. H., Lin, Y. Y., Wu, J. C., & Liu, J. Y. (2014) · PubMed · Cited by 20
Acriflavine suppresses the growth of human osteosarcoma cells through apoptosis and autophagy
Fan, J., Yang, X., & Bi, Z. (2014) · Tumor Biology · doi:10.1007/s13277-014-2156-x · Cited by 19
Kim, S. G., Cho, J., Chung, Y. S., Ahn, E.-T., Lee, K.-Y., & Han, Y.-B. (1998) · PubMed · Cited by 19
Akasaka, T., Tsujii, M., Kondo, J., Hayashi, Y., YING, J., Lu, Y., Kato, M., Yamada, T., Yamamoto, S., Inoue, T., et al. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2693 · Cited by 17
Ma, J., Zhang, Y., Shen, H., Kapesa, L., Liu, W., Zeng, M., & Zeng, S. (2015) · Tumor Biology · doi:10.1007/s13277-015-3723-5 · Cited by 17
Eftekhar, E., Jaberie, H., & Naghibalhossaini, F. (2016) · Europe PMC (PubMed Central) · Cited by 9
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer
Haynes, J., & Manogaran, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26051988 · Cited by 82
Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art
Piórecka, K., Kurjata, J., & Stańczyk, W. A. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00573 · Cited by 67
Oliveira, L. F. S., Predes, D., Borges, H. L., & Abreu, J. G. (2022) · Cancers · doi:10.3390/cancers14020403 · Cited by 38
Repurposing of Acriflavine to Target Chronic Myeloid Leukemia Treatment
Nehme, R., Hallal, R., Dor, M. E., Kobeissy, F. H., Gouilleux, F., Mazurier, F., & Zibara, K. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200908114411 · Cited by 35
Proflavine/acriflavine derivatives with versatile biological activities
Sabolová, D., Kristián, P., & Kožurková, M. (2019) · Journal of Applied Toxicology · doi:10.1002/jat.3818 · Cited by 31
CtNorm: Real time PCR cycle of threshold (Ct) normalization algorithm
Ramezani, A. (2021) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2021.106267 · Cited by 30
Self-citationPolyunsaturated fatty acids and DNA methylation in colorectal cancer
Sarabi, M. M., Khorramabadi, R. M., Zare, Z., & Eftekhar, E. (2019) · World Journal of Clinical Cases · doi:10.12998/wjcc.v7.i24.4172 · Cited by 28
Self-citationFourniols, T., Bastien, E., Canevat, A., Féron, O., & Véronique Préat, A. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119337 · Cited by 28
Effect of Lactate Export Inhibition on Anaplastic Thyroid Cancer Growth and Metabolism
Zhao, B., Aggarwal, A., Im, S.-Y., Viswanathan, K., Landa, I., & Nehs, M. A. (2022) · Journal of the American College of Surgeons · doi:10.1097/xcs.0000000000000226 · Cited by 22
Aghabozorgi, A. S., Sarabi, M. M., Esfehani, R. J., Koochakkhani, S., Hassanzadeh, M., Kavousipour, S., & Eftekhar, E. (2020) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v12.i9.942 · Cited by 23
Self-citationMcDermott, A., & Tavassoli, A. (2024) · Transcription · doi:10.1080/21541264.2024.2417475 · Cited by 17
Novel drug delivery systems in colorectal cancer: Advances and future prospects
Kamal, R., Awasthi, A., Paul, P., Mir, M. S., Singh, S. K., & Dua, K. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155546 · Cited by 13
Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells
Hallal, R., Nehme, R., Brachet‐Botineau, M., Nehme, A., Dakik, H., Deynoux, M., Sbarba, P. D., Vern, Y. L., Zibara, K., Gouilleux, F., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15612 · Cited by 13
The effect of Azo-dyes on glioblastoma cells in vitro
Sevastre, A.-S., Baloi, C., Alexandru, O., Tătăranu, L. G., Popescu, Ş. O., & Dricu, A. (2023) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2023.103599 · Cited by 10
Is acriflavine an efficient co-drug in chemotherapy?
Piórecka, K., Kurjata, J., Gostyński, B., Kaźmierski, S., Stańczyk, W. A., Marcinkowska, M., Janaszewska, A., & Klajnert‐Maculewicz, B. (2023) · RSC Advances · doi:10.1039/d3ra02608f · Cited by 8
Can Zeolite-Supporting Acridines Boost Their Anticancer Performance?
Ranković, M., Jevremović, A., Ležaić, A. J., Arsenijević, A., Rupar, J., Dobričić, V., Vasiljević, B. N., Gavrilov, N. M., Bajuk‐Bogdanović, D., & Milojević‐Rakić, M. (2023) · Journal of Functional Biomaterials · doi:10.3390/jfb14030173 · Cited by 7
Zhang, X., Shan, S., Li, H., Shi, J., Yang, L., & Li, Z. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.03.111 · Cited by 7
Lin, C., Chen, X., Qiu, H., Li, B., & Guo, M. (2022) · Journal of Immunology Research · doi:10.1155/2022/1328542 · Cited by 4
Zargar, P., Koochakkhani, S., Hassanzadeh, M., Taziani, Y. A., Nasrollahi, H., & Eftekhar, E. (2022) · Molecular Biology Reports · doi:10.1007/s11033-021-07087-1 · Cited by 4
Self-citationMarczak, M., Biereg, K., Zadykowicz, B., & Sikorski, A. (2021) · Acta Crystallographica Section C Structural Chemistry · doi:10.1107/s2053229621000681 · Cited by 1
Targeting metabolism: A potential strategy for hematological cancer therapy
Tang, X., Chen, F., Xie, L.-C., Liu, S., & Mai, H. (2022) · World Journal of Clinical Cases · doi:10.12998/wjcc.v10.i10.2990 · Cited by 1
Impact du ciblage du domaine de liaison de HIF-1α avec HIF-1β sur le paysage immunitaire du mélanome
Lequeux, A. (2020) · theses.fr (ABES) · doi:10.70675/a29d12dbz79c1z4d37za978z2e2319131c82
Metadata
- Authors
- Zargar, P., Ghani, E., Mashayekhi, F., Ramezani, A., & Eftekhar, E.
- Affiliations
- Hormozgan University of Medical Sciences (IR)
- Arak University of Medical Sciences (IR)
- Shiraz University of Medical Sciences (IR)
- Venue
- Oncology Letters
- Publisher
- Spandidos Publications
- Published
- 2018-04-25
- Volume
- 15
- Issue
- 6
- Pages
- 10084-10090
- ISSN
- 1792-1074 (ISSN-L)
- 1792-1082
- PMC
- PMC6004650
- OpenAlex
- W2801692758
- Cited by
- 23
- References
- 41
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 3
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Oncology Letters (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hormozgan University of Medical Sciences (91-F-4)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- acriflavine, 5-fluorouracil, colorectal cancer, chemosensitization, irinotecan, p53 status, HIF-1α, topoisomerase II, drug resistance, combination chemotherapy, SW480 cells, HCT116 cells, LS174T cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
