The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy
Open accessAbstract
Chloroquine (CQ) is a 4-aminoquinoline drug used for the treatment of diverse diseases. It inhibits lysosomal acidification and therefore prevents autophagy by blocking autophagosome fusion and degradation. In cancer treatment, CQ is often used in combination with chemotherapeutic drugs and radiation because it has been shown to enhance the efficacy of tumor cell killing. Since CQ and its derivatives are the only inhibitors of autophagy that are available for use in the clinic, multiple ongoing clinical trials are currently using CQ or hydroxychloroquine (HCQ) for this purpose, either alone, or in combination with other anticancer drugs. Here we show that in the mouse breast cancer cell lines, 67NR and 4T1, autophagy is induced by the DNA damaging agent cisplatin or by drugs that selectively target autophagy regulation, the PtdIns3K inhibitor LY294002, and the mTOR inhibitor rapamycin. In combination with these drugs, CQ sensitized to these treatments, though this effect was more evident with LY294002 and rapamycin treatment. Surprisingly, however, in these experiments CQ sensitization occurred independent of autophagy inhibition, since sensitization was not mimicked by Atg12, Beclin 1 knockdown or bafilomycin treatment, and occurred even in the absence of Atg12. We therefore propose that although CQ might be helpful in combination with cancer therapeutic drugs, its sensitizing effects can occur independently of autophagy inhibition. Consequently, this possibility should be considered in the ongoing clinical trials where CQ or HCQ are used in the treatment of cancer, and caution is warranted when CQ treatment is used in cytotoxic assays in autophagy research.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Methods in Mammalian Autophagy Research
Mizushima, N., Yoshimori, T., & Levine, B. (2010) · Cell · doi:10.1016/j.cell.2010.01.028 · Cited by 4,497
Cellular processing of platinum anticancer drugs
Wang, D., & Lippard, S. J. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1691 · Cited by 3,801
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466
Targeting the phosphoinositide 3-kinase pathway in cancer
Liu, P., Cheng, H., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,721
How to Interpret LC3 Immunoblotting
Mizushima, N., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4600 · Cited by 2,669 · cited 2×
“However, LC3II is also degraded inside the lysosomes or de-conjugated by Atg4.(4,24) Therefore, in order to measure autophagic flux, lysosomal inhibitors (CQ, Baf A, pepstatin A/E64D) are used in order to inhibit LC3II degradation, since in the absence of these inhibitors, an autophagy-inducing treatment can result in…”
BackgroundKimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
Klionsky, D. J., Abeliovich, H., Agostinis, P., Agrawal, D. K., Aliev, G., Askew, D. S., Baba, M., Baehrecke, E. H., Bahr, B. A., Ballabio, A., et al. (2008) · Autophagy · doi:10.4161/auto.5338 · Cited by 2,230
Jung, C. H., Ro, S.-H., Cao, J., Otto, N. M., & Kim, D.-H. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.017 · Cited by 2,090
Inhibition of Macroautophagy Triggers Apoptosis
Boya, P., González-Polo, R.-A., Casares, N., Perfettini, J.-L., Dessen, P., Larochette, N., Métivier, D., Meley, D., Souquere, S., Yoshimori, T., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.3.1025-1040.2005 · Cited by 1,625
Pancreatic cancers require autophagy for tumor growth
Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J. M., Dell'Antonio, G., et al. (2011) · Genes & Development · doi:10.1101/gad.2016111 · Cited by 1,498
mTOR and cancer: insights into a complex relationship
Sabatini, D. M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1974 · Cited by 1,322
Aslakson, C. J., & Miller, F. R. (1992) · PubMed · Cited by 1,234
Wu, Y.-T., Tan, H.-L., Shui, G., Bauvy, C., Huang, Q., Wenk, M. R., Ong, C.-N., Codogno, P., & Shen, H.-M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.080796 · Cited by 1,127
Principles and Current Strategies for Targeting Autophagy for Cancer Treatment
Amaravadi, R. K., Lippincott-Schwartz, J., Yin, X.-M., Weiss, W. A., Takebe, N., Timmer, W., DiPaola, R. S., Lotze, M. T., & White, E. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2634 · Cited by 897
Brunn, G. J., Williams, J., Sabers, C., Wiederrecht, G., Lawrence, J. C., & Abraham, R. T. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00911.x · Cited by 723
New insights into the antiviral effects of chloroquine
Savarino, A., Di Trani, L., Donatelli, I., Cauda, R., & Cassone, A. (2006) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(06)70361-9 · Cited by 570
Takeuchi, H., Kondo, Y., Fujiwara, K., Kanzawa, T., Aoki, H., Mills, G. B., & Kondo, S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3640 · Cited by 534
Blocked Autophagy Sensitizes Resistant Carcinoma Cells to Radiation Therapy
Apel, A., Herr, I., Schwarz, H., Rodemann, H. P., & Mayer, A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-0562 · Cited by 523
Autophagy delays apoptotic death in breast cancer cells following DNA damage
Abedin, M. J., Wang, D., McDonnell, M. A., Lehmann, U., & Kelekar, A. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402039 · Cited by 523
Bursch, W., Ellinger, A., Kienzl, H., Török, L., Pandey, S., Sikorska, M., Walker, R., & Hermann, R. S. (1996) · Carcinogenesis · doi:10.1093/carcin/17.8.1595 · Cited by 516
Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies
Solomon, V. R., & Lee, H. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.06.063 · Cited by 516
Maycotte, P., & Thorburn, A. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.2.14627 · Cited by 393
Self-citationAkt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents
Degtyarev, M., De Mazière, A., Orr, C., Lin, J., Lee, B. B., Tien, J. Y., Prior, W. W., van Dijk, S., Wu, H., Gray, D. C., et al. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200801099 · Cited by 366
Katayama, M., Kawaguchi, T., Berger, M. S., & Pieper, R. O. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402030 · Cited by 353
Li, J., Hou, N., Faried, A., Tsutsumi, S., & Kuwano, H. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.02.021 · Cited by 318
Dissecting the dynamic turnover of GFP-LC3 in the autolysosome
Ni, H.-M., Bockus, A., Wozniak, A. L., Jones, K., Weinman, S., Yin, X.-M., & Ding, W.-X. (2011) · Autophagy · doi:10.4161/auto.7.2.14181 · Cited by 318
Autophagy as a therapeutic target in cancer
Chen, N., & Karantza, V. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.2.14622 · Cited by 303
Akt and Autophagy Cooperate to Promote Survival of Drug-Resistant Glioma
Fan, Q.-W., Cheng, C., Hackett, C., Feldman, M., Houseman, B. T., Nicolaides, T., Haas-Kogan, D., James, C. D., Oakes, S. A., Debnath, J., et al. (2010) · Science Signaling · doi:10.1126/scisignal.2001017 · Cited by 295
O’Donovan, T. R., O’Sullivan, G. C., & McKenna, S. L. (2011) · Autophagy · doi:10.4161/auto.7.5.15066 · Cited by 279
Targeting the Phosphoinositide-3 (PI3) Kinase Pathway in Breast Cancer
Baselga, J. (2011) · The Oncologist · doi:10.1634/theoncologist.2011-s1-12 · Cited by 261
Akar, U., Chaves-Reyez, A., Barria, M., Tari, A., Sanguino, A., Kondo, Y., Kondo, S., Arun, B., Lopez-Berestein, G., & Ozpolat, B. (2008) · Autophagy · doi:10.4161/auto.6083 · Cited by 253
Vazquez-Martin, A., Oliveras-Ferraros, C., & Menendez, J. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006251 · Cited by 245
Paglin, S., Lee, N.-Y., Nakar, C., Fitzgerald, M., Plotkin, J., Deuel, B., Hackett, N., McMahill, M., Sphicas, E., Lampen, N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1083 · Cited by 220
2-Deoxy-d-glucose activates autophagy via endoplasmic reticulum stress rather than ATP depletion
Xi, H., Kurtoglu, M., Liu, H., Wangpaichitr, M., You, M., Liu, X., Savaraj, N., & Lampidis, T. J. (2011) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-010-1391-0 · Cited by 205
Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent
Parkhitko, A., Myachina, F., Morrison, T. A., Hindi, K. M., Auricchio, N., Karbowniczek, M., Wu, J. J., Finkel, T., Kwiatkowski, D. J., Yu, J. J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104361108 · Cited by 189
Samaddar, J. S., Gaddy, V. T., Duplantier, J., Thandavan, S. P., Shah, M., Smith, M. J., Browning, D., Rawson, J., Smith, S. B., Barrett, J. T., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0447 · Cited by 189
Gao, P., Bauvy, C., Souquère, S., Tonelli, G., Liu, L., Zhu, Y., Qiao, Z., Bakula, D., Proikas‐Cezanne, T., Pierron, G., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.118125 · Cited by 133
Yu, H., Su, J., Xu, Y., Kang, J., Li, H., Zhang, L., Yi, H., Xiang, X., Liu, F., & Sun, L. (2011) · European Journal of Cancer · doi:10.1016/j.ejca.2011.01.019 · Cited by 130
Zhang, Y., Cheng, Y., Ren, X., Zhang, L., Yap, K. L., Wu, H., Patel, R., Liu, D., Qin, Z.-H., Shih, I., et al. (2011) · Oncogene · doi:10.1038/onc.2011.290 · Cited by 128
Claerhout, S., Verschooten, L., Kelst, S. V., Vos, R. D., Proby, C. M., Agostinis, P., & Garmyn, M. (2010) · International Journal of Cancer · doi:10.1002/ijc.25300 · Cited by 88
The PI3K inhibitor arsenal: choose your weapon!
Crabbe, T., Welham, M. J., & Ward, S. G. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.09.001 · Cited by 84
Jiang, P., Zhao, Y., Deng, X., Mao, Y.-Q., Shi, W., Tang, Q., Li, Z.-G., Zheng, Y., Yang, S., & Wei, Y.-Q. (2010) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2010.06.004 · Cited by 81
Platinum Compounds in the Treatment of Advanced Breast Cancer
Martín, M. (2001) · Clinical Breast Cancer · doi:10.3816/cbc.2001.n.022 · Cited by 79
Hu, C., Solomon, V. R., Ulíbarri, G., & Lee, H. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.07.076 · Cited by 67
Cited by
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationLevy, J. M. M., Towers, C. G., & Thorburn, A. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.53 · Cited by 2,526
Self-citationChloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion
Mauthe, M., Orhon, I., Rocchi, C., Zhou, X., Luhr, M., Hijlkema, K.-J., Coppes, R. P., Engedal, N., Mari, M., & Reggiori, F. (2018) · Autophagy · doi:10.1080/15548627.2018.1474314 · Cited by 2,122
Molecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646
Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment
Sui, X., Chen, R., Wang, Z., Huang, Z., Kong, N., Zhang, M., Han, W., Lou, F., Yang, J., Zhang, Q., et al. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.350 · Cited by 1,204
Metadata
- Authors
- Maycotte, P., Aryal, S., Cummings, C. T., Thorburn, J., Morgan, M. J., & Thorburn, A.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2012-02
- Volume
- 8
- Issue
- 2
- Pages
- 200-212
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2079286948
- Cited by
- 401
- References
- 44
- FWCI
- 22.19
- Type
- journal article
- Language
- en
- Open access
- bronze
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
