Abstract
The interplay between cancer and obesity is multifactorial and complex with the increased risk of cancer development in obese individuals posing a significant threat. Obesity leads to the upregulation or hyperactivation of several oncogenic pathways in cancer cells, which drives them towards a deleterious phenotype. The cross-talk between cancer and obesity is considered a large contributing factor in the development of chemotherapeutic drug resistance and the resistance to radiotherapy. The link between obesity and the development of cancer is so strong that a medication that demonstrates effectiveness against both conditions would serve as an essential step. In this context, anti-obesity medications provide a worthy list of candidates based on their chemo-preventive potential and chemotherapeutic properties. The current study focuses on exploring the potential of anti-obesity medicines as dual anticancer drugs. These medications target several key signaling pathways (e.g., AMPK, PI3K/Akt/mTOR, MAPK, NF-κB, JNK/ERK), which prove to be crucial for both cancer growth and metastases. Some of these drugs also play an important role in attenuating the signaling and cellular events which incite cancer-obesity cross-talk and demonstrate efficient counteraction of neoplastic transformation. Thus, this review highlights a comprehensive view of the potential use of anti-obesity medicines to treat both cancer and obesity for patients exhibiting both comorbities.
Keywords: Obesity, cancer, anti-obesity medicines, phytochemicals, signaling pathways, metastasis.
Graphical Abstract
[http://dx.doi.org/10.1089/ars.2007.1740]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.3389/fonc.2013.00209] [PMID: 23967401]
[http://dx.doi.org/10.1038/nm1087] [PMID: 15286780]
[http://dx.doi.org/10.1155/2013/291546] [PMID: 24073332]
[http://dx.doi.org/10.17795/semj26242]
[http://dx.doi.org/10.1093/jnci/djn415] [PMID: 19116382]
[http://dx.doi.org/10.1073/pnas.0914076107] [PMID: 20457905]
[http://dx.doi.org/10.1038/sj.onc.1201011] [PMID: 9135074]
[http://dx.doi.org/10.1038/nrc1670] [PMID: 16056258]
[http://dx.doi.org/10.1172/JCI39104] [PMID: 19487818]
[http://dx.doi.org/10.1038/nm.2492] [PMID: 22037646]
[http://dx.doi.org/10.1146/annurev-med-050913-022228] [PMID: 25587653]
[http://dx.doi.org/10.1056/NEJMsr1606602] [PMID: 27557308]
[http://dx.doi.org/10.1016/j.ejphar.2015.05.060] [PMID: 26048312]
[http://dx.doi.org/10.1053/j.gastro.2016.12.049] [PMID: 28192104]
[http://dx.doi.org/10.1016/j.pharmthera.2016.10.015] [PMID: 27773782]
[http://dx.doi.org/10.1358/dot.2010.46.12.1556433]
[http://dx.doi.org/10.3390/ph11020055] [PMID: 29849009]
[http://dx.doi.org/10.1038/npp.2010.16] [PMID: 20200509]
[http://dx.doi.org/10.1592/phco.20.4.270.34882] [PMID: 10730683]
[http://dx.doi.org/10.1111/j.1365-2125.2008.03311.x] [PMID: 19220279]
[http://dx.doi.org/10.2337/db17-1385] [PMID: 29776968]
[http://dx.doi.org/10.1007/s13679-018-0300-4] [PMID: 29504049]
[http://dx.doi.org/10.1038/nutd.2017.17] [PMID: 28481334]
[http://dx.doi.org/10.1097/MED.0000000000000095] [PMID: 25105996]
[http://dx.doi.org/10.1111/j.1463-1326.2011.01465.x] [PMID: 21733060]
[http://dx.doi.org/10.1038/clpt.2013.204] [PMID: 24105257]
[http://dx.doi.org/10.1002/biof.1409] [PMID: 29315906]
[http://dx.doi.org/10.3390/nu10091211] [PMID: 30200502]
[http://dx.doi.org/10.1155/2016/9340637] [PMID: 28003714]
[http://dx.doi.org/10.4103/pm.pm_388_17] [PMID: 29720835]
[http://dx.doi.org/10.3390/antiox2040293] [PMID: 26784466]
[http://dx.doi.org/10.1002/ptr.6602] [PMID: 31977122]
[http://dx.doi.org/10.1038/srep07973] [PMID: 25609476]
[http://dx.doi.org/10.1111/obr.12523] [PMID: 28335087]
[http://dx.doi.org/10.1016/j.bbrc.2018.07.168] [PMID: 30093114]
[http://dx.doi.org/10.1038/ncomms6493] [PMID: 25423280]
[http://dx.doi.org/10.1042/BSR20170286] [PMID: 28424369]
[http://dx.doi.org/10.1021/acs.jafc.9b05072] [PMID: 31789021]
[http://dx.doi.org/10.1016/j.cell.2015.05.011] [PMID: 26000480]
[http://dx.doi.org/10.3390/molecules181214892] [PMID: 24304585]
[http://dx.doi.org/10.1016/j.jnutbio.2018.02.012] [PMID: 29621669]
[http://dx.doi.org/10.1016/j.bbalip.2016.08.005] [PMID: 27531277]
[http://dx.doi.org/10.1016/j.jnutbio.2018.10.012] [PMID: 30513433]
[http://dx.doi.org/10.1080/13543784.2018.1471132] [PMID: 29723075]
[http://dx.doi.org/10.3892/mmr.2018.8475] [PMID: 29393459]
[http://dx.doi.org/10.1016/j.ejphar.2017.05.015] [PMID: 28501576]
[http://dx.doi.org/10.1186/s40880-017-0184-9] [PMID: 28126011]
[http://dx.doi.org/10.1093/abbs/gmx106] [PMID: 29342230]
[http://dx.doi.org/10.1371/journal.pone.0209435] [PMID: 30625181]
[http://dx.doi.org/10.1038/s41598-017-11688-x] [PMID: 28916833]
[PMID: 21105456]
[http://dx.doi.org/10.23736/S0026-4806.18.05897-4] [PMID: 30371047]
[http://dx.doi.org/10.7759/cureus.1844] [PMID: 29344438]
[http://dx.doi.org/10.1242/dmm.009621] [PMID: 22915024]
[http://dx.doi.org/10.1021/acs.jafc.9b03997] [PMID: 31419115]
[http://dx.doi.org/10.3390/ijms20010114] [PMID: 30597956]
[http://dx.doi.org/10.3892/ijo.2018.4512] [PMID: 30066852]
[http://dx.doi.org/10.1097/CAD.0000000000000621] [PMID: 29553945]
[http://dx.doi.org/10.1039/C7FO01295K] [PMID: 29185571]
[PMID: 29399197]
[http://dx.doi.org/10.3390/ijms17122109] [PMID: 27983683]
[http://dx.doi.org/10.1186/s12957-018-1400-z] [PMID: 29898731]
[http://dx.doi.org/10.1016/j.bmcl.2017.06.014] [PMID: 28610976]
[http://dx.doi.org/10.1111/jcmm.12749] [PMID: 26648178]
[http://dx.doi.org/10.2174/1871520619666181231112453] [PMID: 30599111]
[http://dx.doi.org/10.1177/1534735413485419] [PMID: 23615751]
[http://dx.doi.org/10.1016/j.heliyon.2018.e00909] [PMID: 30450437]
[http://dx.doi.org/10.3892/or.2018.6292] [PMID: 29512739]
[http://dx.doi.org/10.1111/jfbc.13333] [PMID: 32548903]
[http://dx.doi.org/10.1080/01635581.2019.1651879] [PMID: 31409173]
[http://dx.doi.org/10.1093/carcin/bgs198] [PMID: 22678116]
[http://dx.doi.org/10.1016/j.bbrc.2010.10.063] [PMID: 20971068]
[http://dx.doi.org/10.1007/s10549-008-0227-7] [PMID: 18953692]
[http://dx.doi.org/10.1007/s40495-015-0043-9] [PMID: 26457243]
[http://dx.doi.org/10.1017/S0954422416000044] [PMID: 27172872]
[http://dx.doi.org/10.1002/biof.1400] [PMID: 29210129]
[http://dx.doi.org/10.1080/10408398.2011.585525] [PMID: 24188307]
[http://dx.doi.org/10.1016/j.bbagen.2012.07.010] [PMID: 22877747]
[PMID: 26648205]
[http://dx.doi.org/10.1371/journal.pone.0051702] [PMID: 23240057]
[http://dx.doi.org/10.1177/1947601913486346] [PMID: 23946867]
[http://dx.doi.org/10.5604/01.3001.0010.3801] [PMID: 28258677]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1769] [PMID: 21540236]
[http://dx.doi.org/10.1038/cddis.2012.13] [PMID: 22378068]
[http://dx.doi.org/10.1186/1471-2407-13-235] [PMID: 23663483]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2539]
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2994] [PMID: 19752085]
[http://dx.doi.org/10.1126/science.1116221] [PMID: 16293724]
[http://dx.doi.org/10.1074/jbc.M109.099770] [PMID: 20424164]
[http://dx.doi.org/10.1126/science.1062374] [PMID: 11533489]
[http://dx.doi.org/10.1186/1476-4598-3-11] [PMID: 14749471]
[http://dx.doi.org/10.1586/14737159.7.5.569] [PMID: 17892365]
[http://dx.doi.org/10.1080/15384047.2016.1235661] [PMID: 27686621]
[http://dx.doi.org/10.1016/j.cellsig.2013.03.025] [PMID: 23603750]
[http://dx.doi.org/10.1023/A:1025867130437] [PMID: 15000152]
[http://dx.doi.org/10.3389/fncel.2015.00086] [PMID: 25852478]
[http://dx.doi.org/10.1016/j.molcel.2016.08.009] [PMID: 27618486]
[http://dx.doi.org/10.4161/auto.2149] [PMID: 16874058]
[PMID: 25834400]
[http://dx.doi.org/10.18632/oncotarget.4767] [PMID: 26311737]
[http://dx.doi.org/10.1111/j.1365-2249.2011.04515.x] [PMID: 22235995]
[http://dx.doi.org/10.1155/2012/281261] [PMID: 21876693]
[http://dx.doi.org/10.1038/sj.onc.1209020] [PMID: 16421604]
[http://dx.doi.org/10.1093/jn/137.5.1208] [PMID: 17449583]
[http://dx.doi.org/10.1038/sj.onc.1203239] [PMID: 10602461]
[http://dx.doi.org/10.1007/s11010-010-0540-4] [PMID: 20658310]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4554] [PMID: 21555371]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2807] [PMID: 15833883]
[http://dx.doi.org/10.1016/j.ejphar.2006.03.012] [PMID: 16631160]
[http://dx.doi.org/10.1002/jcb.24386] [PMID: 22961809]
[http://dx.doi.org/10.1007/s13277-013-1169-1] [PMID: 24048756]
[http://dx.doi.org/10.1016/j.ejphar.2015.01.003] [PMID: 25592318]
[http://dx.doi.org/10.1177/1934578X1501000208] [PMID: 25920253]
[PMID: 26884946]
[http://dx.doi.org/10.4103/0970-1591.117278] [PMID: 24082436]
[http://dx.doi.org/10.1124/pr.54.3.375] [PMID: 12223530]
[http://dx.doi.org/10.1038/34112] [PMID: 9422506]
[http://dx.doi.org/10.3390/nu11050945] [PMID: 31035457]
[http://dx.doi.org/10.1080/14737140.2020.1807950] [PMID: 32772585]
[http://dx.doi.org/10.1002/ijc.31392] [PMID: 29569717]
[PMID: 19956878]
[http://dx.doi.org/10.2174/1871520616666160330104413] [PMID: 27025656]
[http://dx.doi.org/10.1371/journal.pone.0121538] [PMID: 25933112]
[http://dx.doi.org/10.1038/nrc1408] [PMID: 15286738]
[http://dx.doi.org/10.1038/ijo.2016.185]
[http://dx.doi.org/10.21037/atm.2019.07.27] [PMID: 31555707]
[http://dx.doi.org/10.1016/j.neuropharm.2017.12.023] [PMID: 29246856]
[http://dx.doi.org/10.2147/VHRM.S6808] [PMID: 18561508]
[http://dx.doi.org/10.1007/s40262-016-0410-7] [PMID: 27193270]
[http://dx.doi.org/10.1007/s40262-015-0343-6] [PMID: 26597252]
[http://dx.doi.org/10.1002/j.1550-8528.1998.tb00314.x] [PMID: 9526970]
[http://dx.doi.org/10.1370/afm.343] [PMID: 16189063]
[http://dx.doi.org/10.1007/s00125-017-4349-5] [PMID: 28770328]
[http://dx.doi.org/10.1097/MOL.0000000000000532] [PMID: 29878903]
[http://dx.doi.org/10.1345/aph.1R501] [PMID: 23482732]
[http://dx.doi.org/10.6118/jmm.2014.20.3.90] [PMID: 25580419]
[http://dx.doi.org/10.2478/folmed-2018-0036] [PMID: 31188761]
[http://dx.doi.org/10.2147/DMSO.S95299] [PMID: 28652791]
[http://dx.doi.org/10.1038/s41598-017-15154-6] [PMID: 29142285]
[http://dx.doi.org/10.1016/j.peptides.2017.09.018] [PMID: 29412831]
[http://dx.doi.org/10.1001/archneur.65.5.577] [PMID: 18474731]
[http://dx.doi.org/10.1016/j.pbb.2010.07.020] [PMID: 20688100]
[http://dx.doi.org/10.1016/j.jnutbio.2017.02.009] [PMID: 28319852]
[http://dx.doi.org/10.1155/2013/575482] [PMID: 23691264]
[http://dx.doi.org/10.1007/s00262-013-1513-8] [PMID: 24363024]
[http://dx.doi.org/10.1016/j.joen.2018.02.023] [PMID: 29680727]
[http://dx.doi.org/10.1016/j.atherosclerosis.2018.06.882] [PMID: 30015296]
[http://dx.doi.org/10.3390/nu11010143] [PMID: 30641865]
[http://dx.doi.org/10.3390/ijms20030535] [PMID: 30695995]
[http://dx.doi.org/10.1111/nyas.13372] [PMID: 28662290]
[http://dx.doi.org/10.1155/2014/834294] [PMID: 25614714]
[http://dx.doi.org/10.3892/ijmm.2014.1921] [PMID: 25189808]
[http://dx.doi.org/10.7150/thno.20270] [PMID: 29158824]
[http://dx.doi.org/10.1097/CAD.0000000000000590] [PMID: 29389802]
[http://dx.doi.org/10.1142/S0192415X18500271] [PMID: 29595072]
[http://dx.doi.org/10.1016/j.saa.2016.06.005] [PMID: 27294548]
[http://dx.doi.org/10.5582/bst.2018.01240] [PMID: 30674760]
[http://dx.doi.org/10.1007/s11418-017-1150-1] [PMID: 29147836]
[http://dx.doi.org/10.3390/ijms18071500] [PMID: 28704925]
[http://dx.doi.org/10.3390/cells8030218] [PMID: 30841634]
[http://dx.doi.org/10.1002/jsfa.6458] [PMID: 24166097]
[http://dx.doi.org/10.1089/jmf.2017.0001] [PMID: 28459647]
[http://dx.doi.org/10.3892/mmr.2017.6321] [PMID: 28447763]
[http://dx.doi.org/10.14336/AD.2016.0620] [PMID: 29344415]
[http://dx.doi.org/10.1021/acs.jafc.5b01246] [PMID: 25929334]
[http://dx.doi.org/10.3390/nu8110731] [PMID: 27869665]
[http://dx.doi.org/10.1111/bph.13514] [PMID: 27174467]
[http://dx.doi.org/10.3390/molecules21080966] [PMID: 27455231]
[PMID: 30272354]
[http://dx.doi.org/10.1007/s00441-018-2803-4] [PMID: 29455258]
[http://dx.doi.org/10.1002/jsfa.6642] [PMID: 24615565]
[http://dx.doi.org/10.3390/ijms19072068] [PMID: 30013004]
[http://dx.doi.org/10.1016/j.ejphar.2014.09.043] [PMID: 25300680]
[http://dx.doi.org/10.1007/978-3-319-41334-1_12] [PMID: 27671821]
[http://dx.doi.org/10.1111/jphp.12744] [PMID: 28481011]
[http://dx.doi.org/10.2174/1568026616666160204123107] [PMID: 26845549]