Abstract
Obesity is a growing epidemic where an abnormal accumulation of fat leads to severe pathological conditions and it recently emerges as an avoidable risk factor for cancer. Obesity fine-tunes the activation of AMPK and PI3K/AKT pathway to induce cancer cell survival, proliferation, metabolism, and genome stability by modulating insulin growth factor signaling, leptin signaling, adiponectin signaling. Autophagy regulates diverse aspects of cellular metabolism and its impairment is associated with obesity-related pathophysiology and its subsequent progression to cancer. Autophagy reduces obesity-induced metabolism dysfunction, inflammation, lipotoxicity, oxidative stress, and proteotoxicity. Autophagy plays a puzzling role in cancer; it prevents cancer initiation in the early stages while leads to cancer development and persistence in later stages. This chapter would link pathways for autophagy dysregulation in obesity and its role in subsequent cancer progression. Accumulated pieces of evidence suggest that modulating autophagy could be an attractive therapeutic intervention for the treatment of obesity-induced cancer.
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References
Abbaszadeh H, Keikhaei B, Mottaghi S (2019) A review of molecular mechanisms involved in anticancer and antiangiogenic effects of natural polyphenolic compounds. Phytother Res 33:2002–2014. https://doi.org/10.1002/ptr.6403
Abdulamir AS, Hafidh RR, Bakar FA (2011) The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role. J Exp Clin Cancer Res 30:11. https://doi.org/10.1186/1756-9966-30-11
Aghajan M, Li N, Karin M, Karin M (2012) Obesity, autophagy and the pathogenesis of liver and pancreatic cancers. J Gastroenterol Hepatol 27:10–14. https://doi.org/10.1111/j.1440-1746.2011.07008.x
Al Dhaheri Y, Attoub S, Ramadan G, Arafat K, Bajbouj K, Karuvantevida N, AbuQamar S, Eid A, Iratni R (2014) Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer. PLoS One 9(10):e109630. https://doi.org/10.1371/journal.pone.0109630
Albiges L, Ari Hakimi A, Xie W, McKay RR, Simantov R, Lin X, Lee JL, Rini BI, Srinivas S, Bjarnason GA, Ernst S, Wood LA, Vaishamayan UN, Rha SY, Agarwal N, Yuasa T, Pal SK, Bamias A, Zabor EC et al (2016) Body mass index and metastatic renal cell carcinoma: clinical and biological correlations. J Clin Oncol 34:3655. https://doi.org/10.1200/JCO.2016.66.7311
Antony J, Masoud J, Salmani M, Jiang Z, Feng L, Song J, Jia X, Chen B (2017) Autophagy : an overview and its roles in cancer and obesity. Clin Chim Acta 468:85–89. https://doi.org/10.1016/j.cca.2017.01.028
Avgerinos KI, Spyrou N, Mantzoros CS, Dalamaga M (2019) Obesity and cancer risk: emerging biological mechanisms and perspectives. Metabolism 92:121–135. https://doi.org/10.1016/j.metabol.2018.11.001
Ballak DB, Stienstra R, Tack CJ, Dinarello CA, van Diepen JA (2015) IL-1 family members in the pathogenesis and treatment of metabolic disease: focus on adipose tissue inflammation and insulin resistance. Cytokine 75:280. https://doi.org/10.1016/j.cyto.2015.05.005
Bardou M, Barkun AN, Martel M (2013) Obesity and colorectal cancer. Gut 62:933–947. https://doi.org/10.1136/gutjnl-2013-304701
Biondo LA, Teixeira AAS, de Ferreira KCOS, Neto JCR (2020) Pharmacological strategies for insulin sensitivity in obesity and cancer: thiazolidinediones and metformin. Curr Pharm Des 26:932. https://doi.org/10.2174/1381612826666200122124116
Brahimi-Horn MC, Chiche J, Pouysségur J (2007) Hypoxia and cancer. J Mol Med 85:1301. https://doi.org/10.1007/s00109-007-0281-3
Bromberg J, Wang TC (2009) Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 15:79–80. https://doi.org/10.1016/j.ccr.2009.01.009
Calle EE, Thun MJ (2004) Obesity and cancer. Oncogene 23:6365. https://doi.org/10.1038/sj.onc.1207751
Chartoumpekis DV, Zaravinos A, Ziros PG, Iskrenova RP, Psyrogiannis AI, Kyriazopoulou VE, Habeos IG (2012) Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice. PLoS One 7(4):e34872. https://doi.org/10.1371/journal.pone.0034872
Che J, Wang W, Huang Y, Zhang L, Zhao J, Zhang P, Yuan X (2019) miR-20a inhibits hypoxia-induced autophagy by targeting ATG5/FIP200 in colorectal cancer. Mol Carcinog 58(7):1234–1247. https://doi.org/10.1002/mc.23006
Cheng Y, Ren X, Hait WN, Yang JM (2013) Therapeutic targeting of autophagy in disease: biology and pharmacology. Pharmacol Rev 65(4):1162–1197. https://doi.org/10.1124/pr.112.007120
Chu SC, Hsieh YS, Yu CC, Lai YY, Chen PN (2014) Thymoquinone induces cell death in human squamous carcinoma cells via caspase activation-dependent apoptosis and LC3-II activation-dependent autophagy. PLoS One 9(7):e101579. https://doi.org/10.1371/journal.pone.0101579
Chu YL, Ho CT, Chung JG, Rajasekaran R, Sheen LY (2012) Allicin induces p53-mediated autophagy in Hep G2 human liver cancer cells. J Agric Food Chem 68(40):11144–11150. https://doi.org/10.1021/jf301298y
Corrêa H, Magalhaes (2019) The impact of the adipose organ plasticity on inflammation and cancer progression. Cell 8:662. https://doi.org/10.3390/cells8070662
Cui YQ, Liu YJ, Zhang F (2018) The suppressive effects of Britannin (Bri) on human liver cancer through inducing apoptosis and autophagy via AMPK activation regulated by ROS. Biochem Biophys Res Commun 497(3):916–923. https://doi.org/10.1016/j.bbrc.2017.12.144
Denduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, Ye J, Wei Q, Wang J, Zhao L, Luu HH (2015) Insulin-like growth factor (IGF) signaling intumorigenesis and the development ofcancer drug resistance. Genes Dis 2:13. https://doi.org/10.1016/j.gendis.2014.10.004
Deretic V, Klionsky DJ (2018) Autophagy and inflammation: a special review issue. Autophagy 14:179. https://doi.org/10.1080/15548627.2017.1412229
Di Zhang L, Liu Z, Liu H, Ran DM, Guo JH, Jiang B, Wu YL, Gao FH (2016) Oridonin enhances the anticancer activity of NVP-BEZ235 against neuroblastoma cells in vitro and in vivo through autophagy. Int J Oncol 49:657. https://doi.org/10.3892/ijo.2016.3557
Ertunc ME, Hotamisligil GS (2016) Lipid signaling and lipotoxicity in metaflammation: indications for metabolic disease pathogenesis and treatment. J Lipid Res 57:2099. https://doi.org/10.1194/jlr.R066514
Fenton JI, Hursting SD, Perkins SN, Hord NG (2006) Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc(min/+) colon epithelial cell line. Carcinogenesis 27:1507. https://doi.org/10.1093/carcin/bgl018
Filomeni G, De Zio D, Cecconi F (2015) Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ 22:377. https://doi.org/10.1038/cdd.2014.150
Galavotti S, Bartesaghi S, Faccenda D, Shaked-Rabi M, Sanzone S, McEvoy A, Dinsdale D, Condorelli F, Brandner S, Campanella M, Grose R, Jones C, Salomoni P (2013) The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells. Oncogene 32:699. https://doi.org/10.1038/onc.2012.111
Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, Codogno P, Debnath J, Gewirtz DA, Karantza V, Kimmelman A, Kumar S, Levine B, Maiuri MC, Martin SJ, Penninger J, Piacentini M, Rubinsztein DC, Simon H et al (2015) Autophagy in malignant transformation and cancer progression. EMBO J 34:856. https://doi.org/10.15252/embj.201490784
Gasche JA, Hoffmann J, Boland CR, Goel A (2011) Interleukin-6 promotes tumorigenesis by altering DNA methylation in oral cancer cells. Int J Cancer 27:1507. https://doi.org/10.1002/ijc.25764
Gilbert CA, Slingerland JM (2013) Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to cancer risk and progression. Annu Rev Med 64:45. https://doi.org/10.1146/annurev-med-121211-091527
Gong K, Zhang Z, Chen Y, Shu HB, Li W (2014) Extracellular signal-regulated kinase, receptor interacting protein, and reactive oxygen species regulate shikonin-induced autophagy in human hepatocellular carcinoma. Eur J Pharmacol 738:142. https://doi.org/10.1016/j.ejphar.2014.05.034
Goodman M (2014) AMPK activators as a drug for diabetes, cancer and cardiovascular disease. Pharmaceut Regul Aff 2:118. https://doi.org/10.4172/2167-7689.1000118
Gossner G, Choi M, Tan L, Fogoros S, Griffith KA, Kuenker M, Liu JR (2007) Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells. Gynecol Oncol 105:23. https://doi.org/10.1016/j.ygyno.2006.11.009
Gottlieb RA (2013) Autophagy in health and disease. In: Autophagy in health and disease. Academic Press, Amsterdam. https://doi.org/10.1016/C2010-0-66523-0
Granato M, Rizzello C, Montani MSG, Cuomo L, Vitillo M, Santarelli R, Gonnella R, D’Orazi G, Faggioni A, Cirone M (2017) Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways. J Nutr Biochem 41:124. https://doi.org/10.1016/j.jnutbio.2016.12.011
Gugnoni M, Sancisi V, Manzotti G, Gandolfi G, Ciarrocchi A (2016) Autophagy and epithelial–mesenchymal transition: an intricate interplay in cancer. Cell Death Dis 7:e2520. https://doi.org/10.1038/cddis.2016.415
Gukovsky I, Li N, Todoric J, Gukovskaya A, Karin M (2013) Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology 144:1199. https://doi.org/10.1053/j.gastro.2013.02.007
He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67. https://doi.org/10.1146/annurev-genet-102808-114910
Heckmann BL, Yang X, Zhang X, Liu J (2013) The autophagic inhibitor 3-methyladenine potently stimulates PKA-dependent lipolysis in adipocytes. Br J Pharmacol 168:163. https://doi.org/10.1111/j.1476-5381.2012.02110.x
Hsin MC, Hsieh YH, Wang PH, Ko JL, Hsin IL, Yang SF (2017) Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells. Cell Death Dis 8:e3089. https://doi.org/10.1038/cddis.2017.459
Hurley JH, Young LN (2017) Mechanisms of autophagy initiation. Annu Rev Biochem 86:225. https://doi.org/10.1146/annurev-biochem-061516-044820
Jacob JA, Salmani JMM, Jiang Z, Feng L, Song J, Jia X, Chen B (2017) Autophagy: an overview and its roles in cancer and obesity. Clin Chim Acta 468:85. https://doi.org/10.1016/j.cca.2017.01.028
Jiang K, Wang W, Jin X, Wang Z, Ji Z, Meng G (2015) Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells. Oncol Rep 3915:4346. https://doi.org/10.3892/or.2015.3915
Johnson R, Shabalala S, Louw J, Kappo AP, Muller CJF (2017) Aspalathin reverts doxorubicin-induced cardiotoxicity through increased autophagy and decreased expression of p53/mTOR/p62 signaling. Molecules 22:1589. https://doi.org/10.3390/molecules22101589
Kao C, Chao A, Tsai CL, Chuang WC, Huang WP, Chen GC, Lin CY, Wang TH, Wang HS, Lai CH (2014) Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation. Cell Death Dis 5:e1510. https://doi.org/10.1038/cddis.2014.468
Kastan MB (2008) DNA damage responses: mechanisms and roles in human disease 2007 - G.H.a. Clowes memorial award lecture. Mol Cancer Res 6:517. https://doi.org/10.1158/1541-7786.MCR-08-0020
Kim AD, Kang KA, Kim HS, Kim DH, Choi YH, Lee SJ, Kim HS, Hyun JW (2013) A ginseng metabolite, compound K, induces autophagy and apoptosis via generation of reactive oxygen species and activation of JNK in human colon cancer cells. Cell Death Dis 4:e750. https://doi.org/10.1038/cddis.2013.273
Krosch TCK, Sangwan V, Banerjee S, Mujumdar N, Dudeja V, Saluja AK, Vickers SM (2013) Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor-kappa B activity. Am J Surg 205:387. https://doi.org/10.1016/j.amjsurg.2013.01.008
Kryston TB, Georgiev AB, Pissis P, Georgakilas AG (2011) Role of oxidative stress and DNA damage in human carcinogenesis. Mutation Res 711:193. https://doi.org/10.1016/j.mrfmmm.2010.12.016
Lavallard VJ, Meijer AJ, Codogno P, Gual P (2012) Autophagy, signaling and obesity. Pharmacol Res 66:513. https://doi.org/10.1016/j.phrs.2012.09.003
Lee HP, Lin CY, Shih JS, Fong YC, Wang SW, Li TM, Tang CH (2015) Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-α pathway. Oncotarget 6:36746. https://doi.org/10.18632/oncotarget.5479
Lee HW, Jang K, Bin S, Choi HJ, Jo A, Cheong JH, Chun KH (2014a) Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy. BMB Rep 47:697. https://doi.org/10.5483/BMBRep.2014.47.12.069
Lee Y, Sung B, Kang YJ, Kim DH, Jang JY, Hwang SY, Kim M, Lim HS, Yoon JH, Chung HY, Kim ND (2014b) Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells. Int J Oncol 44:1599. https://doi.org/10.3892/ijo.2014.2339
Lega IC, Lipscombe LL (2020) Review: diabetes, obesity, and cancer-pathophysiology and clinical implications. Endocr Rev 41:1. https://doi.org/10.1210/endrev/bnz014
Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict? J Clin Investig 115:2679. https://doi.org/10.1172/JCI26390
Li S, Dou X, Ning H, Song Q, Wei W, Zhang X, Shen C, Li J, Sun C, Song Z (2017) Sirtuin 3 acts as a negative regulator of autophagy dictating hepatocyte susceptibility to lipotoxicity. Hepatology 66:936. https://doi.org/10.1002/hep.29229
Li YC, He SM, He ZX, Li M, Yang Y, Pang JX, Zhang X, Chow K, Zhou Q, Duan W, Zhou ZW, Yang T, Huang GH, Liu A, Qiu JX, Liu JP, Zhou SF (2014) Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells. Cancer Lett 344:239. https://doi.org/10.1016/j.canlet.2013.11.001
Liu F, Gao S, Yang Y, Zhao X, Fan Y, Ma W, Yang D, Yang A, Yu Y (2017) Curcumin induced autophagy anticancer effects on human lung adenocarcinoma cell line A549. Oncol Lett 66:513. https://doi.org/10.3892/ol.2017.6565
Liu HY, Han J, Cao SY, Hong T, Zhuo D, Shi J, Liu Z, Cao W (2009) Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia. Inhibition of FoxO1-dependent expression of key autophagy genes by insulin. J Biol Chem 6:284. https://doi.org/10.1074/jbc.M109.033936
Luna-Dulcey L, Tomasin R, Naves MA, da Silva JA, Cominetti MR (2018) Autophagy-dependent apoptosis is triggered by a semi-synthetic [6]-gingerol analogue in triple negative breast cancer cells. Oncotarget 9:30787. https://doi.org/10.18632/oncotarget.25704
Luo Y, Yang Y, Liu M, Wang D, Wang F, Bi Y, Ji J, Li S, Liu Y, Chen R, Huang H, Wang X, Swidnicka-Siergiejko AK, Janowitz T, Beyaz S, Wang G, Xu S, Bialkowska AB, Luo CK et al (2019) Oncogenic KRAS reduces expression of FGF21 in acinar cells to promote pancreatic tumorigenesis in mice on a high-fat diet. Gastroenterology 157:1413. https://doi.org/10.1053/j.gastro.2019.07.030
Maheswari U, Ghosh K, Sadras SR (2018) Licarin a induces cell death by activation of autophagy and apoptosis in non-small cell lung cancer cells. Apoptosis 23:210. https://doi.org/10.1007/s10495-018-1449-8
Manzoni C, Mamais A, Roosen DA, Dihanich S, Soutar MPM, Plun-Favreau H, Bandopadhyay R, Hardy J, Tooze SA, Cookson MR, Lewis PA (2016) MTOR independent regulation of macroautophagy by leucine rich repeat kinase 2 via Beclin-1. Sci Rep 6:35106. https://doi.org/10.1038/srep35106
Mariño G, Martins I, Kroemer G (2011) Autophagy in Ras-induced malignant transformation: fatal or vital? Mol Cell 42:1. https://doi.org/10.1016/j.molcel.2011.03.003
MartÃnez-RodrÃguez OP, Thompson-Bonilla MDR, Jaramillo-Flores ME (2020) Association between obesity and breast cancer: molecular bases and the effect of flavonoids in signaling pathways. Crit Rev Food Sci Nutr 60:3770. https://doi.org/10.1080/10408398.2019.1708262
Mathew R, Karantza-Wadsworth V, White E (2007) Role of autophagy in cancer. Nat Rev Cancer 7:961. https://doi.org/10.1038/nrc2254
Mauthe M, Orhon I, Rocchi C, Zhou X, Luhr M, Hijlkema KJ, Coppes RP, Engedal N, Mari M, Reggiori F (2018) Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy 14:1435. https://doi.org/10.1080/15548627.2018.1474314
Mazure NM, Pouysségur J (2010) Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol 22:177. https://doi.org/10.1016/j.ceb.2009.11.015
Meschini S, Condello M, Marra M, Formisano G, Federici E, Arancia G (2007) Autophagy-mediated chemosensitizing effect of the plant alkaloid voacamine on multidrug resistant cells. Toxicol In Vitro 21:197. https://doi.org/10.1016/j.tiv.2006.09.007
Mizushima N (2007) Autophagy: process and function. Genes Dev 21:2861. https://doi.org/10.1101/gad.1599207
Mohammadi M, Gozashti MH, Aghadavood M, Mehdizadeh MR, Hayatbakhsh MM (2017) Clinical significance of serum IL-6 and TNF-α levels in patients with metabolic syndrome. Rep Biochem Mol Biol 6:74
Muniraj N, Siddharth S, Nagalingam A, Walker A, Woo J, Gyorffy B, Gabrielson E, Saxena NK, Sharma D (2019) Withaferin a inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells. Carcinogenesis 40:1110. https://doi.org/10.1093/carcin/bgz015
Namkoong S, Cho CS, Semple I, Lee JH (2018) Autophagy dysregulation and obesity-associated pathologies. Mol Cells 41:3. https://doi.org/10.14348/molcells.2018.2213
Niture S, Gyamfi MA, Lin M, Chimeh U, Dong X, Zheng W, Moore J, Kumar D (2020) TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation. Cell Death Dis 11:178. https://doi.org/10.1038/s41419-020-2369-4
Pagliassotti MJ, Kim PY, Estrada AL, Stewart CM, Gentile CL (2016) Endoplasmic reticulum stress in obesity and obesity-related disorders: an expanded view. Metabolism 65:1238. https://doi.org/10.1016/j.metabol.2016.05.002
Park D, Jeong H, Lee MN, Koh A, Kwon O, Yang YR, Noh J, Suh PG, Park H, Ryu SH (2016) Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition. Sci Rep 6:21772. https://doi.org/10.1038/srep21772
Park J, Morley TS, Kim M, Clegg DJ, Scherer PE (2014) Obesity and cancer - mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol 40:455. https://doi.org/10.1038/nrendo.2014.94
Park SH, Park HS, Lee JH, Chi GY, Kim GY, Moon SK, Chang YC, Hyun JW, Kim WJ, Choi YH (2013) Induction of endoplasmic reticulum stress-mediated apoptosis and non-canonical autophagy by luteolin in NCI-H460 lung carcinoma cells. Food Chem Toxicol 49:1. https://doi.org/10.1016/j.fct.2013.02.022
Patra S, Mishra SR, Behera BP, Mahapatra KK, Panigrahi DP, Bhol CS, Praharaj PP, Sethi G, Patra SK, Bhutia SK (2020) Autophagy-modulating phytochemicals in cancer therapeutics: current evidences and future perspectives. Semin Cancer Biol. Academic Press. https://doi.org/10.1016/j.semcancer.2020.05.008
Pereira RI, Leitner JW, Erickson C, Draznin B (2008) Pioglitazone acutely stimulates adiponectin secretion from mouse and human adipocytes via activation of the phosphatidylinositol 3′-kinase. Life Sci 83:638. https://doi.org/10.1016/j.lfs.2008.09.002
Popa C, Netea MG, Van Riel PLCM, Van Der Meer JWM, Stalenhoef AFH (2007) The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 89:64. https://doi.org/10.1194/jlr.R600021-JLR200
Procaccini C, Lourenço E, Matarese G, Cava A (2009) Leptin signaling: a key pathway in immune responses. Current Sig Trans Therapy 4:22. https://doi.org/10.2174/157436209787048711
Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, Cattoretti G, Levine B (2003) Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Investig 112:1809. https://doi.org/10.1172/JCI20039
Quail DF, Dannenberg AJ (2019) The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol 15:139. https://doi.org/10.1038/s41574-018-0126-x
Ramadori P, Li X, Heikenwalder M (2020) PKCλ/ι loss induces metabolic reprogramming in liver cancer: hitting two birds with one stone? Cancer Cell 38(2):152–154. https://doi.org/10.1016/j.ccell.2020.07.003
Rasul A, Yu B, Zhong L, Khan M, Yang H, Ma T (2012) Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy. Oncol Rep 27:1487. https://doi.org/10.3892/or.2012.1694
Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL (2004) Secretion of Angiogenic and Antiapoptotic factors by human adipose stromal cells. Circulation 4:8. https://doi.org/10.1161/01.CIR.0000121425.42966.F1
Roca-Agujetas V, De Dios C, Lestón L, Marà M, Morales A, Colell A (2019) Recent insights into the mitochondrial role in autophagy and its regulation by oxidative stress. Oxid Med Cell Longev 184:2066. https://doi.org/10.1155/2019/3809308
Roy B, Pattanaik AK, Das J, Bhutia SK, Behera B, Singh P, Maiti TK (2014) Role of PI3K/Akt/mTOR and MEK/ERK pathway in concanavalin a induced autophagy in HeLa cells. Chem Biol Interact 210:96. https://doi.org/10.1016/j.cbi.2014.01.003
Rubinsztein DC, Codogno P, Levine B (2012) Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 11:709. https://doi.org/10.1038/nrd3802
Rubinsztein DC, Mariño G, Kroemer G (2011) Autophagy and aging. Cell 146:682. https://doi.org/10.1016/j.cell.2011.07.030
Saha S, Panigrahi DP, Patil S, Bhutia SK (2018) Autophagy in health and disease: a comprehensive review. Biomed Pharmacother 10:572. https://doi.org/10.1016/j.biopha.2018.05.007
Schmid D, Ricci C, Behrens G, Leitzmann MF (2015) Adiposity and risk of thyroid cancer: a systematic review and meta-analysis. Obes Rev 16:1042. https://doi.org/10.1111/obr.12321
Selvakumaran M, Amaravadi RK, Vasilevskaya IA, O’Dwyer PJ (2013) Autophagy inhibition sensitizes colon cancer cells to antiangiogenic and cytotoxic therapy. Clin Cancer Res 19:2995. https://doi.org/10.1158/1078-0432.CCR-12-1542
Singh BN, Kumar D, Shankar S, Srivastava RK (2012) Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. Biochem Pharmacol 84:1154. https://doi.org/10.1016/j.bcp.2012.08.007
Sun JW, Zhao LG, Yang Y, Ma X, Wang YY, Xiang YB (2015) Obesity and risk of bladder cancer: a dose-response meta-analysis of 15 cohort studies. PLoS One 10:e0119313. https://doi.org/10.1371/journal.pone.0119313
Sun ZL, Dong JL, Wu J (2017) Juglanin induces apoptosis and autophagy in human breast cancer progression via ROS/JNK promotion. Biomed Pharmacother 85:303. https://doi.org/10.1016/j.biopha.2016.11.030
Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S, Eishi Y, Hino O, Tanaka K, Mizushima N (2011) Autophagy-deficient mice develop multiple liver tumors. Genes Dev 25:795. https://doi.org/10.1101/gad.2016211
Tan J, Xianzhen J, Yin G, He L, Liu J, Zhi L, Zhiqiang J, Yao K (2017) Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway. Oncol Rep 38:1373. https://doi.org/10.3892/or.2017.5841
Tan KT, Lin MX, Lin SC, Tung YT, Lin SH, Lin CC (2019) Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma. Anticancer Drugs 30:485. https://doi.org/10.1097/CAD.0000000000000756
Tian Y, Xu H, Farooq AA, Nie B, Chen X, Su S, Yuan R, Qiao G, Li C, Li X, Liu X, Lin X (2018) Maslinic acid induces autophagy by down-regulating HSPA8 in pancreatic cancer cells. Phytother Res 32:1320. https://doi.org/10.1002/ptr.6064
Uchiyama Y, Shibata M, Koike M, Yoshimura K, Sasaki M (2008) Autophagy-physiology and pathophysiology. Histochem Cell Biol 129:407. https://doi.org/10.1007/s00418-008-0406-y
Vessoni AT, Filippi-Chiela EC, Menck CFM, Lenz G (2013) Autophagy and genomic integrity. Cell Death Differ 20:1444. https://doi.org/10.1038/cdd.2013.103
Vucenik I, Stains JP (2012) Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci 1271:37. https://doi.org/10.1111/j.1749-6632.2012.06750.x
Wang B, Zhou TY, Nie CH, Wan DL, Zheng SS (2018b) Bigelovin, a sesquiterpene lactone, suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation in liver cancer. Biochem Biophys Res Commun 499:156. https://doi.org/10.1016/j.bbrc.2018.03.091
Wang H, Liu T, Li L, Wang Q, Yu C, Liu X, Li W (2015) Tetrandrine is a potent cell autophagy agonist via activated intracellular reactive oxygen species. Cell Biosci 5:4. https://doi.org/10.1186/2045-3701-5-4
Wang Y, Xu W, Yan Z, Zhao W, Mi J, Li J, Yan H (2018a) Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways. J Exp Clin Cancer Res 37:63. https://doi.org/10.1186/s13046-018-0731-5
Wang Y, Li L, Hou C, Lai Y, Long J, Liu J, Zhong Q, Diao J (2016) SNARE-mediated membrane fusion in autophagy. Semin Cell Dev Biol 60:97. https://doi.org/10.1016/j.semcdb.2016.07.009
White E (2016) Autophagy and p53. Cold Spring Harb Perspect Med 6:a026120. https://doi.org/10.1101/cshperspect.a026120
White E, DiPaola RS (2009) The double-edged sword of autophagy modulation in cancer. Clin Cancer Res 15:5308. https://doi.org/10.1158/1078-0432.CCR-07-5023
Wu S, Lu H, Bai Y (2019) Nrf2 in cancers: a double-edged sword. Cancer Med 8:2252. https://doi.org/10.1002/cam4.2101
Xiong XX, Liu JM, Qiu XY, Pan F, Yu SB, Chen XQ (2015) Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways. Acta Pharmacol Sin 36(3):362–374. https://doi.org/10.1038/aps.2014.141
Xu J, Zhang XQ, Zhang Z (2020) Transcription factor EB agonists from natural products for treating human diseases with impaired autophagy-lysosome pathway. Chin Med 20:1. https://doi.org/10.1186/s13020-020-00402-1
Yang PM, Tseng HH, Peng CW, Chen WS, Chiu SJ (2012) Dietary flavonoid fisetin targets caspase-3-deficient human breast cancer MCF-7 cells by induction of caspase-7-associated apoptosis and inhibition of autophagy. Int J Oncol 40:469. https://doi.org/10.3892/ijo.2011.1203
Yang Z, Klionsky DJ (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol 12:814. https://doi.org/10.1038/ncb0910-814
Yoon YS, Kwon AR, Lee YK, Oh SW (2019) Circulating adipokines and risk of obesity related cancers: a systematic review and meta-analysis. Obes Res Clin Pract 13:329. https://doi.org/10.1016/j.orcp.2019.03.006
Youl E, Bardy G, Magous R, Cros G, Sejalon F, Virsolvy A, Richard S, Quignard JF, Gross R, Petit P, Bataille D, Oiry C (2010) Quercetin potentiates insulin secretion and protects INS-1 pancreatic -cells against oxidative damage via the ERK1/2 pathway. Br J Pharmacol 161:799. https://doi.org/10.1111/j.1476-5381.2010.00910.x
Young ARJ, Narita M, Ferreira M, Kirschner K, Sadaie M, Darot JFJ, Tavaré S, Arakawa S, Shimizu S, Watt FM, Narita M (2009) Autophagy mediates the mitotic senescence transition. Genes Dev 23:784. https://doi.org/10.1101/gad.519709
Yu R, Zhang Z, Wang B, Jiang H, Cheng L, Shen L (2014) Berberine-induced apoptotic and autophagic death of HepG2 cells requires AMPK activation. Cancer Cell Int 14:49. https://doi.org/10.1186/1475-2867-14-49
Yuan G, Yan SF, Xue H, Zhang P, Sun JT, Li G (2014) Cucurbitacin i induces protective autophagy in glioblastoma in vitro and in vivo. J Biol Chem 289:10607. https://doi.org/10.1074/jbc.M113.528760
Yun CW, Lee SH (2018) The roles of autophagy in cancer. Int J Mol Sci 19:3466. https://doi.org/10.3390/ijms19113466
Zachari M, Ganley IG (2017) The mammalian ULK1 complex and autophagy initiation. Essays Biochem 61:585. https://doi.org/10.1042/EBC20170021
Zhang JW, Zhang SS, Song JR, Sun K, Zong C, Zhao QD, Liu WT, Li R, Wu MC, Wei LX (2014) Autophagy inhibition switches low-dose camptothecin-induced premature senescence to apoptosis in human colorectal cancer cells. Biochem Pharmacol 90:265. https://doi.org/10.1016/j.bcp.2014.05.009
Zhang Y, Sowers JR, Ren J (2018) Targeting autophagy in obesity: from pathophysiology to management. Nat Rev Endocrinol 14:356. https://doi.org/10.1038/s41574-018-0009-1
Zhao C, Yin S, Dong Y, Guo X, Fan L, Ye M, Hu H (2013) Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. Autophagy 9:196. https://doi.org/10.4161/auto.22805
Zhao R, Chen M, Jiang Z, Zhao F, Xi B, Zhang X, Fu H, Zhou K (2015) Platycodin-D induced autophagy in non-small cell lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathways. J Cancer 6:623. https://doi.org/10.7150/jca.11291
Zhao Z, Chen Y (2014) Oridonin, a promising antitumor natural product in the chemotherapy of hematological malignancies. Curr Pharm Biotechnol 15:1083. https://doi.org/10.2174/1389201015666141111115608
Zhou J, Li G, Zheng Y, Shen HM, Hu X, Ming QL, Huang C, Li P, Gao N (2015) A novel autophagy/mitophagy inhibitor liensinine sensitizes breast cancer cells to chemotherapy through DNM1L-mediated mitochondrial fission. Autophagy 11:1259. https://doi.org/10.1080/15548627.2015.1056970
Zou M, Hu C, You Q, Zhang A, Wang X, Guo Q (2015) Oroxylin a induces autophagy in human malignant glioma cells via the mTOR-STAT3-notch signaling pathway. Mol Carcinog 54:1363. https://doi.org/10.1002/mc.22212
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Authors are thankful to the Department of Biotechnology, MNNIT Allahabad, India for the facilitation and support.
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Kushwaha, A., Agarwal, V. (2021). Autophagy at the Crossroad of Obesity-Mediated Cancer Progression. In: Kumar, S., Gupta, S. (eds) Obesity and Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-16-1846-8_16
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