Abstract
Plants are a source of diverse classes of secondary metabolites with anticancer properties. Paclitaxel (Taxol) is an anticancer drug isolated from various Taxus species and is used as a chemotherapeutic agent against various cancers. The biosynthesis of paclitaxel is a complex pathway, making its total chemical synthesis commercially non-viable; hence, alternative novel sources - like plant cell culture and heterologous expression systems, are being investigated to overcome this issue. Advancements in the field of genetic engineering, microbial fermentation engineering, and recombinant techniques have significantly increased the achievable yields of paclitaxel. Indeed, paclitaxel selectively targets microtubules and causes cell cycle arrest in the G2/M phase, inducing a cytotoxic effect in a concentration and time-dependent manner. Innovative drug delivery formulations, like the development of albumin-bound nanoparticles, nano-emulsions, nano-suspensions, liposomes, and polymeric micelles, have been applied to enhance the delivery of paclitaxel to tumor cells. This review focuses on the production, biosynthesis, mechanism of action, and anticancer effects of paclitaxel.
Keywords: Paclitaxel, taxol, biosynthesis, anticancer, nanomedicine, cancer.
[http://dx.doi.org/10.1091/mbc.e14-04-0916] [PMID: 25213191]
[http://dx.doi.org/10.3390/molecules25245986] [PMID: 33348838]
[http://dx.doi.org/10.1093/annonc/mdu025] [PMID: 24667715]
[http://dx.doi.org/10.1007/s13277-015-3365-7] [PMID: 25833695]
[http://dx.doi.org/10.1186/s11658-019-0164-y] [PMID: 31223315]
[http://dx.doi.org/10.1002/med.20242] [PMID: 21381049]
[http://dx.doi.org/10.3892/ol.2017.6211] [PMID: 28693250]
[http://dx.doi.org/10.1186/s12885-021-08441-z] [PMID: 34275458]
[PMID: 12006516]
[http://dx.doi.org/10.1016/j.jconrel.2013.05.041] [PMID: 23770008]
[http://dx.doi.org/10.1097/CAD.0000000000000063] [PMID: 24413390]
[http://dx.doi.org/10.1038/277665a0] [PMID: 423966]
[http://dx.doi.org/10.1073/pnas.77.3.1561] [PMID: 6103535]
[http://dx.doi.org/10.1093/jnci/82.15.1247] [PMID: 1973737]
[http://dx.doi.org/10.1016/S0031-9422(01)00218-7] [PMID: 11551566]
[http://dx.doi.org/10.1016/j.procbio.2010.09.004]
[http://dx.doi.org/10.1021/ja00083a067]
[http://dx.doi.org/10.1038/367630a0] [PMID: 7906395]
[http://dx.doi.org/10.1016/j.nbt.2014.02.010] [PMID: 24614567]
[http://dx.doi.org/10.1038/nbt0996-1129] [PMID: 9631065]
[http://dx.doi.org/10.1023/A:1005658405449]
[http://dx.doi.org/10.1007/s00253-009-1856-4] [PMID: 19172266]
[http://dx.doi.org/10.1126/science.8097061] [PMID: 8097061]
[http://dx.doi.org/10.1099/13500872-142-2-435] [PMID: 8932715]
[http://dx.doi.org/10.1099/13500872-142-8-2223] [PMID: 8760934]
[http://dx.doi.org/10.1111/j.1574-6968.2000.tb09432.x] [PMID: 11111032]
[PMID: 12795852]
[http://dx.doi.org/10.2478/s11536-011-0074-5]
[http://dx.doi.org/10.1007/s00299-015-1902-x] [PMID: 26620815]
[http://dx.doi.org/10.1007/10_2008_103] [PMID: 18594786]
[http://dx.doi.org/10.1007/BF00039691]
[http://dx.doi.org/10.1038/nbt.1693] [PMID: 20972422]
[http://dx.doi.org/10.1038/nchembio.2007.8] [PMID: 17576426]
[http://dx.doi.org/10.1006/jmbi.2001.5077] [PMID: 11700061]
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0552] [PMID: 20978163]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3914] [PMID: 17440056]
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.01.018] [PMID: 20083194]
[http://dx.doi.org/10.1074/jbc.272.27.17118] [PMID: 9202030]
[http://dx.doi.org/10.3109/1547691X.2012.655343] [PMID: 22449053]
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.1016/j.semcancer.2019.12.022] [PMID: 31891780]
[http://dx.doi.org/10.3892/or.2017.5593] [PMID: 28440434]
[http://dx.doi.org/10.3390/biom9120789] [PMID: 31783552]
[http://dx.doi.org/10.1074/jbc.M309523200] [PMID: 14527951]
[http://dx.doi.org/10.1016/0959-8049(95)00641-9] [PMID: 8814705]
[http://dx.doi.org/10.1007/s00280-008-0738-2] [PMID: 18365196]
[http://dx.doi.org/10.1200/JCO.1998.16.10.3353] [PMID: 9779712]
[http://dx.doi.org/10.1200/JCO.2003.02.063] [PMID: 12637460]
[http://dx.doi.org/10.3892/or.2013.2359] [PMID: 23525624]
[http://dx.doi.org/10.1056/NEJMoa1809615] [PMID: 30345906]
[http://dx.doi.org/10.1200/JCO.1996.14.6.1858] [PMID: 8656254]
[http://dx.doi.org/10.1378/chest.117.4_suppl_1.152S] [PMID: 10777471]
[http://dx.doi.org/10.1093/oxfordjournals.annonc.a059324] [PMID: 8589023]
[http://dx.doi.org/10.1016/j.lungcan.2019.09.020] [PMID: 31654836]
[http://dx.doi.org/10.1016/S0022-5223(00)70016-X] [PMID: 10733772]
[http://dx.doi.org/10.18632/oncotarget.27519] [PMID: 32362998]
[http://dx.doi.org/10.1111/j.1349-7006.1997.tb00350.x] [PMID: 9473739]
[http://dx.doi.org/10.3892/mco.2019.1828] [PMID: 30967948]
[http://dx.doi.org/10.1200/JCO.2011.39.5848] [PMID: 22547591]
[http://dx.doi.org/10.1155/2015/413076] [PMID: 26137480]
[http://dx.doi.org/10.7326/0003-4819-111-4-273] [PMID: 2569287]
[PMID: 10190787]
[http://dx.doi.org/10.1159/000287968] [PMID: 20185937]
[http://dx.doi.org/10.1016/j.ygyno.2007.03.019] [PMID: 17466362]
[http://dx.doi.org/10.1016/j.biomaterials.2012.05.060] [PMID: 22717365]
[http://dx.doi.org/10.1093/jnci/djg036] [PMID: 12953086]
[http://dx.doi.org/10.1200/JCO.1993.11.12.2405] [PMID: 7902426]
[http://dx.doi.org/10.1016/S0140-6736(03)13718-X] [PMID: 12826431]
[PMID: 14607056]
[http://dx.doi.org/10.1056/NEJM199601043340101] [PMID: 7494563]
[http://dx.doi.org/10.21873/anticanres.14294] [PMID: 32487607]
[PMID: 15628759]
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2117] [PMID: 18347149]
[http://dx.doi.org/10.1002/ijc.20405] [PMID: 15352049]
[PMID: 19578772]
[PMID: 11212279]
[http://dx.doi.org/10.1016/S0022-5347(05)00891-8] [PMID: 16600800]
[http://dx.doi.org/10.1200/JCO.1997.15.9.3156] [PMID: 9294479]
[http://dx.doi.org/10.1002/cncr.22068] [PMID: 16832814]
[http://dx.doi.org/10.1016/S0022-5347(05)64164-X] [PMID: 12441936]
[http://dx.doi.org/10.1016/j.carbpol.2011.04.082]
[http://dx.doi.org/10.1016/j.jconrel.2004.07.006] [PMID: 15380635]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2182] [PMID: 31831565]
[http://dx.doi.org/10.1021/acs.molpharmaceut.9b01215] [PMID: 31944768]
[http://dx.doi.org/10.1016/j.biomaterials.2014.03.049] [PMID: 24726749]
[http://dx.doi.org/10.1016/j.biomaterials.2013.07.075] [PMID: 23932498]
[http://dx.doi.org/10.1007/s10147-011-0220-8] [PMID: 21455624]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-1356] [PMID: 23918602]
[http://dx.doi.org/10.1186/s12885-018-5244-2] [PMID: 30621618]
[http://dx.doi.org/10.1200/JCO.2011.36.5742] [PMID: 21969517]
[http://dx.doi.org/10.1159/000334704] [PMID: 22187539]
[http://dx.doi.org/10.1007/s00280-012-1979-7] [PMID: 23053263]
[http://dx.doi.org/10.1097/COC.0b013e3182436e8c] [PMID: 22307213]
[http://dx.doi.org/10.1093/annonc/mdr379] [PMID: 21896540]
[http://dx.doi.org/10.3109/07357900903179591] [PMID: 19968498]