234
Views
1
CrossRef citations to date
0
Altmetric
Research Articles

Cytotoxic and apoptotic effects of some (R)-carvone-isoxazoline derivatives on human fibrosarcoma and carcinoma cells: experimental evaluation for cytotoxicity, molecular docking and molecular dynamics studies

, , , , , , , ORCID Icon, , & ORCID Icon show all
Pages 1930-1943 | Received 25 Jun 2021, Accepted 31 Dec 2021, Published online: 11 Jan 2022

References

  • Anil, A. D., Akinalp, G., Sanli, F., Ali, Y. M., Gambacorta, N., Nicolotti, O., Omer, F. K., Oztekin, A., & Burmaoglu, S. (2020). Design, synthesis and biological evaluation of 3,5-diaryl isoxazole derivatives as potential anticancer agents. Bioorganic & Medicinal Chemistry Letters, 30(19), 127427. https://doi.org/10.1016/j.bmcl.2020.127427
  • Benbacer, L., Merghoub, N. M., El Btaouri, H., Gmouh, S., Attaleb, M., Morjani, H., Amzazi, S., & El Mzibri, M. (2012). Antiproliferative effect and induction of apoptosis by inulaviscosa L and retamamonosperma L. Extracts in human cervical cancer cells. In R. Rajkumar (Ed.), Topics on cervical cancer with an advocacy for prevention (pp. 267–284). IntechOpen. https://doi.org/10.5772/30025
  • Bicas, J. L., Neri-Numa, I. A., Ruiz, A. L. T. G., D-Carvalho, J. E., & Pastore, G. M. (2011). Evaluation of the antioxidant and antiproliferative potential of bioflavors. Food and Chemical Toxicology, 49(7), 1610–1615. https://doi.org/10.1016/j.fct.2011.04.012
  • Bimoussa, A., Oubella, A., Hachim, M. E., Fawzi, M., Ait Itto, M. Y., Mentre, O., Ketatni, E. M., Bahsis, L., Morjani, H., & Auhmani, A. (2021). New enaminone sesquiterpenic: TiCl4-catalyzed synthesis, spectral characterization, crystal structure, Hirshfeld surface analysis, DFT studies and cytotoxic activity. Journal of Molecular Structure, 1241, 130622. https://doi.org/10.1016/j.molstruc.2021.130622
  • Bimoussa, A., Oubella, A., Laamari, Y., Fawzi, M., Hachim, M. E., Ait Itto, M. Y., Mentre, O., Ketatni, E. M., Morjani, H., & Auhmani, A. (2021). Hybrid of the 1,2,3‐triazole nucleus and sesquiterpene skeleton as a potential antitumor agent: Hemisynthesis, molecular structure, Hirshfeld surface analysis, DFT, in vitro cytotoxic and apoptotic effects. Journal of Heterocyclic Chemistry, 58(12), 2334–2347. https://doi.org/10.1002/jhet.4359
  • Byrappa, S., Harsha, R. M., Kungyal, T., Kudva, N. N. U., Salimath, B. P., & Lokanatha, R. K. M. (2017). Synthesis and biological evaluation of novel isoxazolines linked via piperazine to 2-benzoisothiazoles as potent apoptotic agents. European Journal of Medicinal Chemistry, 126, 218–224. https://doi.org/10.2174/1874104501711010196
  • Circu, M. L., & Aw, T. K. (2010). Reactive oxygen species, cellular redox systems, and apoptosis. Free Radical Biology & Medicine, 48(6), 749–762. https://doi.org/10.1016/j.freeradbiomed.2009.12.022
  • Conklin, K. A. (2004). Cancer chemotherapy and antioxidants. The Journal of Nutrition, 134(11), 3201S–3204S. https://doi.org/10.1093/jn/134.11.3201S
  • Conradt, B. (2009). Genetic control of programmed cell death during animal development. Annual Review of Genetics, 43, 493–523. https://doi.org/10.1146/annurev.genet.42.110807.091533
  • Domínguez, F. X., Villa, N., Durán-Iturbide, A., & Ávila-Zárraga, J. G. (2021). Synthesis, molecular docking, and in silico ADME/Tox profiling studies of new 1-aryl-5-(3-azidopropyl)indol-4-ones: Potential inhibitors of SARS CoV-2 main protease. Bioorganic Chemistry, 106, 104497. doi: https://doi.org/10.1016/j.bioorg.2020.104497
  • Eccles, S. A., Massey, A., Raynaud, F. I., Sharp, S. Y., Box, G., Valenti, M., Patterson, L., Brandon, A. D., Gowan, S., Boxall, F., Aherne, W., Rowlands, M., Hayes, A., Martins, V., Urban, F., Boxall, K., Prodromou, C., Pearl, L., James, K., … Workman, P. (2008). NVP-AUY922: A novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Research, 68(8), 2850–2860. https://doi.org/10.1158/0008-5472.CAN-07-5256
  • El Mansouri, A.-E., Oubella, A., Dânoun, K., Ahmad, M., Neyts, J., Jochmans, D., Snoeck, R., Andrei, G., Morjani, H., Zahouily, M., & Lazrek, H. B. (2021). Discovery of novel furo[2,3-d]pyrimidin-2-one–1,3,4-oxadiazole hybrid derivatives as dual antiviral and anticancer agents that induce apoptosis. Archiv Der Pharmazie, 354(10), e2100146. https://doi.org/10.1002/ardp.202100146
  • El Mansouri, A.-E., Oubella, A., Maatallah, M., Ait Itto, M. Y., Zahouily, M., Morjani, H., & Lazrek, H. B. (2020). Design, synthesis, biological evaluation and molecular docking of new uracil analogs-1,2,4-oxadiazole hybrids as potential anticancer agents. Bioorganic & Medicinal Chemistry Letters, 30(19), 127438. https://doi.org/10.1016/j.bmcl.2020.127438
  • El Mansouri, A. E., Zahouily, M., & Lazrek, H. B. (2019). HMDS/KI is a simple, cheap and efficient catalyst for the one-pot synthesis of N-functionalized pyrimidines. Synthetic Communications., 49(14), 1802–1812. https://doi.org/10.1080/00397911.2019.1602655
  • Fawzi, M., Laamari, Y., Koumya, Y., Oubella, A., Auhmani, A., Itto, A., My, Y., Abouelfida, A., Riahi, A., & Aumani, A. (2021). Electrochemical and theorecal studies on the corrosion inhibition performance of some synthesized D-Limonene based hterocyclic compounds. Journal of Molecular Structure, 1244(2021), 130957. https://doi.org/10.1016/j.molstruc.2021.130957
  • Feddouli, A., Ait Itto, M. Y., Ait Ali, M., Hasnaoui, A., & Riahi, A. (2006). Efficient approach for the synthesis of novel functionalized isoxazolines from limonene. Synthetic Communications., 36(23), 3617–3624. https://doi.org/10.1080/00397910600943709
  • Feddouli, A., Ait Itto, M. Y., Hasnaoui, A., Villemin, D., Jaffres, P.-A., Oliveira, D., Riahi, A., Huet, F., & Daran, J.-C. (2004). One pot diastereoselective synthesis of new chiral spiro1,3,4-thiadiazoles and 1,4,2èoxathiazoles from (1R)-thiocamphor. Journal of Heterocyclic Chemistry, 41(5), 731–735. https://doi.org/10.1002/jhet.5570410513
  • Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., Repasky, M. P., Knoll, E. H., Shelley, M., Perry, J. K., Shaw, D. E., Francis, P., & Shenkin, P. S. (2004). Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. Journal of Medicinal Chemistry, 47 (7), 1739–1749. https://doi.org/10.1021/jm0306430
  • Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., Sanschagrin, P. C., & Mainz, D. T. (2006). Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. Journal of Medicinal Chemistry, 49 (21), 6177–6196. https://doi.org/10.1021/jm051256o
  • Fulda, S., & Debatin, K.-M. (2006). Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 25(34), 4798–4811. https://doi.org/10.1038/sj.onc.1209608
  • Galzitskaya, O. V., & Garbuzynskiy, S. O. (2006). Entropy capacity determines protein folding. Proteins, 63(1), 144–154. https://doi.org/10.1002/prot.20851
  • Gopalakrishnan, T., Ganapathy, S., Veeran, V., & Namasivayam, N. (2019). Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 111, 178–187. https://doi.org/10.1016/j.biopha.2018.12.071
  • Hasanain, A. O., Salam, W. A., Ali, A. M., Ahmed, F. H., Rayshan, A. M., & Suhad, S. H. (2020). Molecular docking and dynamics simulation of FDA approved drugs with the main protease from novel coronavirus. Bioinformation, 16 (3), 236–244. https://doi.org/10.6026/97320630016236
  • Hengartner, M. O. (2000). The biochemistry of apoptosis. Nature, 407(6805), 770–776. https://doi.org/10.1038/35037710
  • Igney, F. K., & Krammer, P. H. (2002). Death and anti-death: Tumour resistance to apoptosis. Nature Reviews. Cancer, 2(4), 277–288. https://doi.org/10.1038/nrc776
  • Jacobs, J. P., Jones, C. M., & Baille, J. P. (1970). Characteristics of a human diploid cell designated MRC-5. Nature, 227(5254), 168–170. https://doi.org/10.1155/2020/7415672
  • Jayashankara, B., & Rai, K. L. (2008). Synthesis and evaluation of antimicrobial activity of a new series of bis (isoxazoline) derivatives. Arkivoc, 2008(11), 75–85. https://doi.org/10.3998/ark.5550190.0009.b07
  • Jensen, M. R., Schoepfer, J., Radimerski, T., Massey, A., Guy, C. T., Brueggen, J., Quadt, C., Buckler, A., Cozens, R., Drysdale, M. J., Garcia-Echeverria, C., & Chene, P. (2008). NVP-AUY922: A small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Research, 10(2), 1–12. https://doi.org/10.1186/bcr1996
  • Kaffy, J., Pontikis, R., Carrez, D., Croisy, A., Monneret, C., & Florent, J.-C. (2006). Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation. Bioorganic & Medicinal Chemistry, 14(12), 4067–4077. https://doi.org/10.1016/j.bmc.2006.02.001
  • Kamal, A., Reddy, J. S., Ramaiah, M. J., Dastagiri, D., Bharathi, E. V., & Azhar, M. A., Sultana, F., Pushpavalli, S. N. C. V. L., Pal-Bhadra, M., Juvekar, A., Sen, S., & Zingde, S. (2010). Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents. European Journal of Medicinal Chemistry., 45(9), 3924–3937. https://doi.org/10.1016/j.ejmech.2010.05.047
  • Kaufmann, S. H., & Hengartner, M. O. (2001). Programmed cell death: Alive and well in the new millennium. Trends in Cell Biology, 11(12), 526–534. https://doi.org/10.1016/S0962-8924(01)02173-0
  • Kaur, K., Kumar, V., Sharma, A. K., & Gupta, G. K. (2014). Isoxazoline containing natural products as anticancer agents: A review. European Journal of Medicinal Chemistry, 77(22), 121–133. https://doi.org/10.1016/j.ejmech.2014.02.063
  • Kesornpun, C., Aree, T., Mahidol, C., Ruchirawat, S., & Kittakoop, P. (2016). Water-assisted nitrile oxide cycloadditions: Synthesis of isoxazoles and stereoselective syntheses of isoxazolines and 1,2,4-oxadiazoles. Angewandte Chemie (International ed. in English), 55(12), 3997–4001. https://doi.org/10.1002/anie.201511730
  • Krieger, E., Darden, T., Nabuurs, S. B., Finkelstein, A., & Vriend, G. (2004). Making optimal use of empirical energy functions: Force-field parameterization in crystal space. Proteins, 57(4), 678–683. https://doi.org/10.1002/prot.20251
  • Laamari, Y., Oubella, A., Bimoussa, A., El Mansouri, Az, E., Ketatni, El, M., Mentre, O., Ait Itto, M. Y., Morjani, H., Khouili, M., & Auhmani, A. (2021). Design, hemiysnthesis, crystal structure and anticancer activity of 1, 2, 3-triazoles derivatives of totarol. Bioorganic Chemistry, 115, 105165. https://doi.org/10.1016/j.bioorg.2021.105165
  • Lee, E. F., Harris, T. J., Tran, S., Evangelista, M., Arulananda, S., John, T., Ramnac, C., Hobbs, C., Zhu, H., Gunasingh, G., Segal, D., Behren, A., Cebon, J., Dobrovic, A., Mariadason, J. M., Strasser, A., Rohrbeck, L., Haass, N. K., Herold, M. J., & Fairlie, W. D. (2019). BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival. Cell Death & Disease, 10(5), 1–14. https://doi.org/10.1038/s41419-019-1568-3
  • Lin, C. M., Ho, H. H., Pettit, G. R., & Hamel, E. (1989). Antimitotic natural products combretastatin A-4 and combretastatin A-2: Studies on the mechanism of their inhibition of the binding of colchicine to tubulin. Biochemistry, 28(17), 6984–6991. https://doi.org/10.1021/bi00443a031
  • Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221–234. https://doi.org/10.1007/s10822-013-9644-8
  • Manikandan, P., & Nagini, S. (2018). Cytochrome P450 structure, function and clinical significance: A review. Current Drug Targets, 19(1), 38–54. https://doi.org/10.2174/1389450118666170125144557
  • Mouhi, E. H., Oubella, A., Byadi, S., Fawzi, M., Laamari, Y., Bahsis, L., Aboulmouhajir, A., Morjani, H., Črtomir, P., Auhmani, A., & Ait Itto, M. Y. (2021). Newly synthesized (R)-carvone-derived 1,2,3-triazoles: Structural, mechanistic, cytotoxic and molecular docking studies. Journal of Biomolecular Structure and Dynamics, 1–14.   https://doi.org/10.1080/07391102.2021.1894984
  • Moussaoui, O., Byadi, S., Eddine Hachim, M., Sghyar, R., Bahsis, L., Moslova, K., Aboulmouhajir, A., Rodi, Y. K., Podlipnik, Č., Hadrami, E. M. E., & Chakroune, S. (2021). Selective synthesis of novel quinolones-amino esters as potential antibacterial and antifungal agents: Experimental, mechanistic study, docking and molecular dynamic simulations. Journal of Molecular Structure, 1241, 130652. https://doi.org/10.1016/j.molstruc.2021.130652
  • Negi, A., & Murphy, P. V. (2021). Development of Mcl-1 inhibitors for cancer therapy. European Journal of Medicinal Chemistry, 210, 113038. https://doi.org/10.1016/j.ejmech.113038.
  • Norouzi, S., Norouzi, M., Amini, M., Amanzadeh, A., Nabiuni, M., & Irian, S. (2016). Two COX-2 inhibitors induce apoptosis in human erythroleukemia K562cells by modulating NF-κB and FHC pathways. DARU, J. Pharm, Sci, 24(1), 1. https://doi.org/10.1186/s40199-015-0139-0.
  • Oubella, A., Ait Itto, M. Y., Auhmani, A., Riahi, A., Daran, J.-C., & Auhmani, A. (2020). Crystal structure of (R)-5-[(R)-3-(4-chloro-phen-yl)-5-methyl-4,5-di-hydro-isoxazol-5-yl]-2-methyl-cyclo-hex-2-enone. Acta Crystallographica. Section E, Crystallographic Communications, 76(Pt 3), 400–403. https://doi.org/10.1107/S2056989020001991
  • Oubella, A., Ait Itto, M. Y., Auhmani, A., Riahi, A., Robert, A., Daran, J.-C., Morjani, H., Parish, C. A., & Esseffar, M. (2019). Diastereoselective synthesis and cytotoxic evaluation of new isoxazoles and pyrazoles with monoterpenic skeleton. Journal of Molecular Structure., 1198, 126924. https://doi.org/10.1016/j.molstruc.2019.126924
  • Oubella, A., El Mansouri, A.-E., Fawzi, M., Bimoussa, A., Laamari, Y., Auhmani, A., a., Morjani, H., Robert, A., Riahi, A., & Ait Itto, M. Y. (2021). Thiazolidinone-linked1,2,3-triazoles with monoterpenic skeleton as new potential anticancer agents: Design, synthesis and molecular docking studies. Bioorganic Chemistry, 115, 105184. https://doi.org/10.1016/j.bioorg.2021.105184
  • Oubella, A., Fawzi, M., Auhmani, A., Riahi, A., Morjani, H., Robert, A., & Ait Itto, M. Y. (2020). Synthesis and antitumor activity of novel heterocyclic systems with monoterpenic skeleton combining dichlorocyclopropane and 1,3,4-thiadiazole nucleus. ChemistrySelect, 5(21), 6403–6406. https://doi.org/10.1002/slct.202001284
  • Pearl, L. H., & Prodromou, C. (2006). Structure and mechanism of the Hsp90 molecular chaperone machinery. Annual Review of Biochemistry, 75, 271–294. https://doi.org/10.1146/annurev.biochem.75.103004.142738
  • Pettit, G. R., Cragg, G. M., & Singh, S. B. (1987). Antineoplastic agents, 122. Constituents of Combretum caffrum. Journal of Natural Products, 50(3), 386–391. https://doi.org/10.1021/np50051a008
  • Pettit, G. R., Temple, C., Narayanan, V. L., Varma, R., Simpson, M. J., Boyd, M. R., Rener, G. A., & Bansal, N. C. (1995). Antineoplastic agents 322. Synthesis of combretastatin A-4 prodrugs. Anti-Cancer Drug Design, 45(8), 1697–1711.
  • Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58 (9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104.
  • Rajib, I., Rimon, P., Archi, S. P., Nizam, U., Md, S. R., Abdulla, A.-M., Md, N. H., Md, A. A., & Mohammad, A. H. (2020). A molecular modeling approach to identify effective antiviral phytochemicals against the main protease of SARS-CoV-2. Journal of Biomolecular Structure and Dynamics, 39(9), 3213–3224. https://doi.org/10.1080/07391102.2020.1761883
  • Rasool, F., Nayak, D., Katoch, A., Faheem, M. M., Yousuf, S. K., Hussain, N., Belawal, C., Satti, N. K., Goswami, A., & Mukherjee, D. (2017). Regiospecific synthesis of ring A fused withaferin A isoxazoline analogues: Induction of premature senescence by W-2b in proliferating cancer cells. Scientific Reports, 7(1), 13749. https://doi.org/10.1038/s41598-017-13664-x
  • Ríos-Gutiérrez, M., Domingo, L. R., Esseffar, M., Oubella, A., & Ait Itto, M. Y. (2020). Unveiling the different chemical reactivity of diphenyl nitrilimine and phenyl nitrile oxide in [3 + 2] cycloaddition reactions with (R)-carvone through the molecular electron density theory. Molecules, 25(5), 1085. https://doi.org/10.3390/molecules25051085
  • Sairi, A. M. M., Ismail, S. I., Sukor, A., Rashid, N. M. N., Saad, N., Jamian, S., & Abdullah, S. (2020). Cytotoxicity and anticancer activity of donkioporiella mellea on MRC5 (normal human lung) and A549 (human lung carcinoma) cells lines. Evidence-Based Complementary and Alternative Medicine, 2020, 1–10. https://doi.org/10.1155/2020/7415672
  • Shi, L., Hu, R., Wei, Y., Liang, Y., Yang, Z., & Ke, S. (2012). Anthranilic acid-based diamides derivatives incorporating aryl-isoxazoline pharmacophore as potential anticancer agents: Design, synthesis and biological evaluation. European Journal of Medicinal Chemistry, 54(54), 549–556. https://doi.org/10.1016/j.ejmech.2012.06.001
  • Simoni, D., Grisolia, G., Giannini, G., Roberti, M., Rondanin, R., Piccagli, L., Baruchello, R., Rossi, M., Romagnoli, R., Invidiata, F. P., Grimaudo, S., Jung, M. K., Hamel, E., Gebbia, N., Crosta, L., Abbadessa, V., Di Cristina, A., Dusonchet, L., Meli, M., & Tolomeo, M. (2005). Heterocyclic and phenyl double-bond-locked combretastatin analogues possessing potent apoptosis-inducing activity in HL60 and in MDR cell lines. Journal of Medicinal Chemistry, 48(3), 723–736. https://doi.org/10.1021/jm049622b
  • Stravopodis, D. J., Margaritis, L. H., & Voutsinas, G. E. (2007). Drug-mediated targeted disruption of multiple protein activities through functional inhibition of the Hsp90 chaperone complex. Current Medicinal Chemistry, 14(29), 3122–3138. https://doi.org/10.2174/092986707782793925
  • Taia, A., Essaber, M., Oubella, A., Aatif, A., Bodiguel, J., Jamart-Grégoire, B., Ait Itto, M. Y., & Morjani, H. (2020). Synthesis, characterization, and biological evaluation of new heterocyclic systems 1,2,3- triazole-isoxazoline from eugenol by the mixed condensation reactions. Synthetic Communications., 50(13), 2052–2065. https://doi.org/10.1080/00397911.2020.1762224
  • Taldone, T., Gozman, A., Maharaj, R., & Chiosis, G. (2008). Targeting Hsp90: Small-molecule inhibitors and their clinical development. Current Opinion in Pharmacology, 8(4), 370–374. https://doi.org/10.1016/j.coph.2008.06.015
  • Tolomeo, M., & Simoni, D. (2002). Drug resistance and apoptosis in cancer treatnent: Development of new apoptosis-inducing agents active in drug resistant malignancies. Current Medicinal Chemistry, 2, 387–401. https://doi.org/10.2174/1568011024606361
  • Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 65(2), 87–108. https://doi.org/10.3322/caac.21262
  • Tron, A. E., Belmonte, M. A., Adam, A., Aquila, B. M., Boise, L. H., Chiarparin, E., Cidado, J., Embrey, K. J., Gangl, E., Gibbons, F. D., Gregory, G. P., Hargreaves, D., Hendricks, J. A., Johannes, J. W., Johnstone, R. W., Kazmirski, S. L., Kettle, J. G., Lamb, M. L., Matulis, S. M., … Hird, A. W. (2018). Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia. Nature Communications, 9(1), 1–14. https://doi.org/10.1038/s41467-018-07551-w
  • Wandinger, S. K., Richter, K., & Buchner, J. (2008). The Hsp90 chaperone machinery. The Journal of Biological Chemistry, 283(27), 18473–11877. https://doi.org/10.1074/jbc.R800007200
  • Wang, L., Woods, K. W., Li, Q., Barr, K. J., Mc, Croskey, R. W., Hannick, S. M., Gherke, L., Credo, R. B., Hui, Y. A., Marsh, K., Warner, R., Lee, J. Y., Zielinski, M. N., Frost, D., Rosenberg, S. H., & Sham, H. L. (2002). Potent, orally active heterocycle-based combretastatin A-4 analogues: Synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. Journal of Medicinal Chemistry, 45(8), 1697–1711. https://doi.org/10.1021/jm010523x
  • Whitesell, L., & Lindquist, S. L. (2005). HSP90 and the chaperoning of cancer. Nature Reviews. Cancer, 5(10), 761–772. https://doi.org/10.1038/nrc1716
  • Wong, R. S. Y. (2011). Apoptosis in cancer: From pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research : CR, (30), 87. https://doi.org/10.1186/1756-9966-30-87
  • Workman, P. (2004). Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone. Cancer Letters, 206(2), 149–157. https://doi.org/10.1016/j.canlet.2003.08.032
  • Zhang, H., & Burrows, F. (2004). Targeting multiple signal transduction pathways through inhibition of Hsp90. Journal of Molecular Medicine (Berlin, Germany), 82(8), 488–499. https://doi.org/10.1007/s00109-004-0549-9
  • Zhivotovsky, B., & Orrenius, S. (2003). Defects in apoptotic machinery of cancer cells: Role in drug resistance. Seminars in Cancer Biology, 13(2), 125–134. https://doi.org/10.1016/S1044-579X(02)00130-X

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.