Modulation of Autophagy in Cancer Cells by Dietary Polyphenols

Pérez-Hernández, M., Arias, A., Martínez-García, D., Pérez-Tomás, R., Quesada, R., and Soto-Cerrato, V. (2019). Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization. Cancers, 11.

Wu, M.-Y., and Lu, J.-H. (2020). Autophagy and Macrophage Functions: Inflammatory Response and Phagocytosis. Cells, 9.

Sahu, 2011, Microautophagy of Cytosolic Proteins by Late Endosomes, Dev. Cell., 20, 131, 10.1016/j.devcel.2010.12.003

White, 2015, The role for autophagy in cancer (White, 2015), J. Clin. Investig., 125, 42, 10.1172/JCI73941

Hao, 2019, Targetome analysis of chaperone-mediated autophagy in cancer cells, Autophagy, 15, 1558, 10.1080/15548627.2019.1586255

Dikic, 2018, Mechanism and medical implications of mammalian autophagy, Nat. Rev. Mol. Cell Biol., 19, 349, 10.1038/s41580-018-0003-4

Lim, 2020, Targeting Autophagy to Treat Cancer: Challenges and Opportunities, Front. Pharmacol., 11, 590344, 10.3389/fphar.2020.590344

Kimmelman, 2011, The dynamic nature of autophagy in cancer, Genes Dev., 25, 1999, 10.1101/gad.17558811

Janji, 2018, Targeting Autophagy in the Tumor Microenvironment: New Challenges and Opportunities for Regulating Tumor Immunity, Front. Immunol., 9, 887, 10.3389/fimmu.2018.00887

Liu, 2012, Autophagy and cancer—Issues we need to digest, J. Cell Sci., 12, 2349

Patel, 2007, Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis, Genes Dev., 21, 1621, 10.1101/gad.1565707

Jin, 2008, Tumor suppression by autophagy through the management of metabolic stress, Autophagy, 4, 563, 10.4161/auto.5830

Follo, 2019, Autophagy facilitates the release of immunogenic signals following chemotherapy in 3D models of mesothelioma, Mol. Carcinog., 58, 1754, 10.1002/mc.23050

Li, 2020, Autophagy and autophagy-related proteins in cancer, Mol. Cancer, 19, 12, 10.1186/s12943-020-1138-4

Shimgu, 2009, Inhibition of autophagy at a late stage enhances imatinib-induced cytotoxicity In human malignant glioma cells, Int. J. Cancer., 124, 1060, 10.1002/ijc.24030

Liu, 2011, Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in esophageal squamous cell carcinoma cells, Med. Oncol., 28, 105, 10.1007/s12032-009-9397-3

Selvakumaran, 2013, Autophagy inhibition sensitizes colon cancer cells to antiangiogenic and cytotoxic therapy, Clin. Cancer Res., 19, 2995, 10.1158/1078-0432.CCR-12-1542

Boya, 2005, Inhibition of Macroautophagy Triggers Apoptosis, Mol. Cell. Biol., 25, 1025, 10.1128/MCB.25.3.1025-1040.2005

Lu, 2018, Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965, EBioMedicine, 34, 85, 10.1016/j.ebiom.2018.07.034

Hanahan, 2011, Hallmarks of cancer: the next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013

Ojha, 2015, Autophagy in Cancer Stem Cells: A Potential Link between Chemoresistance, Recurrence, and Metastasis, BioResearch Open Access, 4, 97, 10.1089/biores.2014.0035

2020, The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity, Front. Oncol., 10, 578418, 10.3389/fonc.2020.578418

Hardie, 2007, AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy, Nat. Rev. Mol. Cell Biol., 8, 774, 10.1038/nrm2249

Yoshida, 2017, Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment, J. Hematol. Oncol., 9, 10

Kim, 2011, AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1, Nat. Cell Biol., 13, 132, 10.1038/ncb2152

Bedoui, 2020, Emerging connectivity of programmed cell death pathways and its physiological implications, Nat. Rev. Mol. Cell Biol., 21, 678, 10.1038/s41580-020-0270-8

Jung, 2020, Autophagy as a decisive process for cell death, Exp. Mol. Med., 52, 921, 10.1038/s12276-020-0455-4

Galluzzi, 2017, Molecular definitions of autophagy and related processes, EMBO J., 36, 1811, 10.15252/embj.201796697

Klionsky, 2016, Guidelines for the use and interpretation of assays for monitoring autophagy (3rd ed.), Autophagy, 12, 1, 10.1080/15548627.2015.1100356

Galluzzi, 2018, Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018, Cell Death Differ., 25, 486, 10.1038/s41418-017-0012-4

Dasari, 2017, Signalome-wide RNAi screen identifies GBA1 as a positive mediator of autophagic cell death, Cell Death Differ., 24, 1288, 10.1038/cdd.2017.80

Fan, 2020, Resveratrol modulates the apoptosis and autophagic death of human lung adenocarcinoma A549 cells via a p53 dependent pathway: Integrated bioinformatics analysis and experimental validation, Int. J. Oncol., 57, 925

Li, 2020, Ferroptosis: past, present and future, Cell Death Dis., 11, 88, 10.1038/s41419-020-2298-2

Yoshida, 2020, The interplay between apoptosis and ferroptosis mediated by ER stress, Apoptosis, 25, 784, 10.1007/s10495-020-01641-1

Sui, 2013, Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment, Cell Death Dis., 4, 838, 10.1038/cddis.2013.350

Wang, 2019, LncRNA SNHG6 promotes chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in colorectal cancer cells, Cancer Cell Int., 19, 234, 10.1186/s12935-019-0951-6

Li, 2020, MiTF is Associated with Chemoresistance to Cisplatin in A549 Lung Cancer Cells via Modulating Lysosomal Biogenesis and Autophagy, Cancer Manag. Res., 12, 6563, 10.2147/CMAR.S255939

Kiruthiga, C., Devi, K.P., Nabavi, S.M., and Bishayee, A. (2020). Autophagy: A Potential Therapeutic Target of Polyphenols in Hepatocellular Carcinoma. Cancers, 12.

Zarfeshany, 2014, Potent health effects of pomegranate, Adv. Biomed. Res., 3, 100, 10.4103/2277-9175.129371

Xu, 2020, Metabolomic analysis of acerola cherry (Malpighia emarginata) fruit during ripening development via UPLC-Q-TOF and contribution to the antioxidant activity, Food Res. Int., 130, 108915, 10.1016/j.foodres.2019.108915

Xia, 2010, Biological activities of polyphenols from grapes, Int. J. Mol. Sci., 11, 622, 10.3390/ijms11020622

Musial, C., Kuban-Jankowska, A., and Gorska-Ponikowska, M. (2020). Beneficial Properties of Green Tea Catechins. Int. J. Mol. Sci., 21.

Arranz, 2012, Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer, Nutrients, 4, 759, 10.3390/nu4070759

Kapuy, 2014, mTOR inhibition increases cell viability via autophagy induction during endoplasmic reticulum stress—an experimental and modeling study, FEBS OpenBio, 4, 704, 10.1016/j.fob.2014.07.006

Karthikeyan, 2017, Insights on the involvement of (−)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration, Apoptosis, 22, 72, 10.1007/s10495-016-1318-2

Lee, 2015, EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone deacetylase in primary neuron cells, Oncotarget, 6, 9701, 10.18632/oncotarget.3832

Holczer, 2015, A comprehensive systems biological study of autophagy-apoptosis crosstalk during endoplasmic reticulum stress, BioMed Res. Int., 2015, 319589, 10.1155/2015/319589

Holczer, 2018, Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress, Oxidative Med. Cell. Longev., 2018, 6721530, 10.1155/2018/6721530

Tsai, C.Y., Chen, C.Y., and Chiou, Y.H. (2017). Epigallocatechin-3-gallate suppresses human herpesvirus 8 replication and induces ROS leading to apoptosis and autophagy in primary effusion lymphoma cells. Int. J. Mol. Sci., 19.

Grube, 2018, Achievable central nervous system concentrations of the green tea catechin EGCG induce stress in glioblastoma cells in vitro, Nutr. Cancer, 70, 1145, 10.1080/01635581.2018.1495239

Abdal, D.A., Choi, H.Y., Yang, G.M., Kim, K., Saha, S.K., and Cho, S.G. (2016). The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms. Nutrients, 8.

Zhou, Y., Zheng, J., Li, Y., Xu, D.P., Li, S., Chen, Y.M., and Li, H.B. (2016). Natural Polyphenols for Prevention and Treatment of Cancer. Nutrients, 8.

Izdebska, 2015, Green tea extract induces protective autophagy in A549 non-small lung cancer cell line, Postepy Hig. Med. Dosw., 31, 1478

Minnelli, C., Laudadio, E., Mobbili, G., and Galeazzi, R. (2020). Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents. Int. J. Mol. Sci., 21.

Meng, 2019, EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC, Onco Targets Ther., 12, 6033, 10.2147/OTT.S209441

Modernelli, 2015, EGCG antagonizes Bortezomib cytotoxicity in prostate cancer cells by an autophagic mechanism, Sci. Rep., 5, 15270, 10.1038/srep15270

Wang, 2018, SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition, J. Exp. Clin. Cancer Res., 37, 37, 10.1186/s13046-018-0689-3

Przychodzen, 2019, Anticancer Potential of Oleuropein, the Polyphenol of Olive Oil, With 2-Methoxyestradiol, Separately or in Combination, in Human Osteosarcoma Cells, Anticancer Res., 39, 1243, 10.21873/anticanres.13234

Lu, 2020, Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion via Induction of Autophagy in ER-Positive Breast Cancer Cell Lines (MCF7 and T47D), Nutr. Cancer, 14, 1

Imran, 2018, Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates, J. Food Sci., 83, 1781, 10.1111/1750-3841.14198

Grossi, C., Rigacci, S., Ambrosini, S., Ed Dami, T., Luccarini, I., Traini, C., Failli, P., Berti, A., Casamenti, F., and Stefani, M. (2013). The polyphenol oleuropein aglycone protects TgCRND8 mice against AΔ plaque pathology. PLoS ONE, 8.

Rigacci, 2015, Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: A mechanistic insight, Oncotarget, 6, 35344, 10.18632/oncotarget.6119

Porcu, C., Sideri, S., Martini, M., Cocomazzi, A., Galli, A., Tarantino, G., and Balsano, C. (2018). Oleuropein Induces AMPK-Dependent Autophagy in NAFLD Mice, Regardless of the Gender. Int. J. Mol. Sci., 19.

Stacchiotti, 2020, Natural Compounds and Autophagy: Allies Against Neurodegeneration, Front Cell Dev. Biol., 22, 555409, 10.3389/fcell.2020.555409

Turrini, 2015, Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy, Oxidative Med. Cell. Longev., 2015, 938475, 10.1155/2015/938475

Mehta, 2004, Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture, Eur. J. Cancer Prev., 13, 345, 10.1097/01.cej.0000136571.70998.5a

Aslam, 2006, Pomegranate as a cosmeceutical source: Pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells, J. Ethnopharmacol., 103, 311, 10.1016/j.jep.2005.07.027

Malik, 2005, Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer, Proc. Natl. Acad. Sci. USA, 102, 14813, 10.1073/pnas.0505870102

Larrosa, 2006, The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway, J. Nutr. Biochem., 17, 611, 10.1016/j.jnutbio.2005.09.004

Khan, 2007, Pomegranate fruit extract inhibits prosurvival pathways in human A549 lung carcinoma cells and tumor growth in athymic nude mice, Carcinogenesis, 28, 163, 10.1093/carcin/bgl145

Syed, 2006, Photochemopreventive effect of pomegranate fruil extract on UVA-mediated activation of cellular pathways in normal human epidermal keratinocytes, Photochem. Photobiol., 82, 398, 10.1562/2005-06-23-RA-589

Malik, 2006, Prostate cancer prevention through pomegranate fruit, Cell Cycle, 5, 371, 10.4161/cc.5.4.2486

Seeram, 2005, In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice, J Nutr Biochem., 16, 360, 10.1016/j.jnutbio.2005.01.006

Gil, 2000, Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing, J. Agric. Food Chem., 48, 4581, 10.1021/jf000404a

Wang, 2013, Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells, Acta Pharmacol. Sin., 34, 1411, 10.1038/aps.2013.98

Tan, 2019, Pomegranate activates TFEB to promote autophagy-lysosomal fitness and mitophagy, Sci. Rep., 9, 727, 10.1038/s41598-018-37400-1

Mezadri, 2008, Antioxidant compounds and antioxidant activity in acerola (Malpighia emarginata DC.) fruits and derivatives, J. Food Compost. Anal., 21, 282, 10.1016/j.jfca.2008.02.002

Sung, 2016, Role of Apigenin in Cancer Prevention via the Induction of Apoptosis and Autophagy, J. Cancer Prev., 21, 216, 10.15430/JCP.2016.21.4.216

Tong, 2012, Apigenin, a chemopreventive bioflavonoid, induces AMP-activated protein kinase activation in human keratinocytes, Mol. Carcinog., 51, 268, 10.1002/mc.20793

Jeremic, 2013, The mechanisms of in vitro cytotoxicity of mountain tea, Sideritis scardica, against the C6 glioma cell line, Planta Med., 79, 516

Rimando, 2004, Resveratrol, pterostilbene, and piceatannol in vaccinium berries, J. Agric. Food Chem., 52, 4713, 10.1021/jf040095e

Liu, 2003, Comparative characterization of peanuts grown by aquatic floating cultivation and field cultivation for seed and resveratrol production, J. Agric. Food Chem., 51, 1582, 10.1021/jf025963r

Wang, 2002, An LC-MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine, J. Agric. Food Chem., 50, 431, 10.1021/jf010812u

Stojanovic, 2001, Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analogues in the radical liposome oxidation, Arch. Biochem. Biophys., 391, 79, 10.1006/abbi.2001.2388

Szewczuk, 2004, Resveratrol is a peroxidase mediated inactivator of COX-1 but not COX-2: A mechanistic approach to the design of COX-1 selective agents, J. Biol. Chem., 279, 22727, 10.1074/jbc.M314302200

Cao, 2004, Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury, Eur. J. Pharmacol., 489, 39, 10.1016/j.ejphar.2004.02.031

Rivera, 2009, Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats, Biochem. Pharmacol., 77, 1053, 10.1016/j.bcp.2008.11.027

Jang, 1997, Cancer chemopreventive activity of resveratrol, a natural product derived from grapes, Science, 275, 218, 10.1126/science.275.5297.218

Fan, Y., Chiu, J.F., Liu, J., Deng, Y., Xu, C., Zhang, J., and Li, G. (2018). Resveratrol induces autophagy-dependent apoptosis in HL-60 cells. BMC Cancer, 18.

Wozniak, 2019, The wine polyphenol resveratrol modulates autophagy and induces apoptosis in MOLT-4 and HL-60 human leukemia cells, J. Physiol. Pharmacol., 70, 1

Puissant, 2010, Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation, Cancer Res., 70, 1042, 10.1158/0008-5472.CAN-09-3537

Ge, 2013, Resveratrol induces apoptosis and autophagy in T-cell acute lymphoblastic leukemia cells by inhibiting Akt/mTOR and activating p38-MAPK, Biomed. Environ. Sci., 26, 902

Yan, 2014, Resveratrol induces human K562 cell apoptosis, erythroid differentiation, and autophagy, Tumour Biol., 35, 5381, 10.1007/s13277-014-1701-y

Wang, 2014, Resveratrol triggers protective autophagy through the ceramide/Akt/mTOR pathway in melanoma B16 cells, Nutr. Cancer, 66, 435, 10.1080/01635581.2013.878738

Gong, 2020, Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway, Exp. Ther. Med., 19, 1878

Li, J., Qin, Z., and Liang, Z. (2009). The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells. BMC Cancer, 9.

Liu, 2018, Resveratrol-mediated apoptosis in renal cell carcinoma via the p53/AMP activated protein kinase/mammalian target of rapamycin autophagy signaling pathway, Mol. Med. Rep., 17, 502

Tang, 2013, Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma, Cancer Lett., 336, 325, 10.1016/j.canlet.2013.03.023

Zhang, 2018, Resveratrol inhibited the progression of human hepatocellular carcinoma by inducing autophagy via regulateng p53 and the phosphoinositide 3 kinase/protein kinase B pathway, Oncol. Rep., 40, 2758

Miki, 2012, Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells, Int. J. Oncol., 40, 1020, 10.3892/ijo.2012.1325

Li, 2013, Dietary resveratrol prevents development of high-grade prostatic intraepithelial neoplastic lesions: involvement of SIRT1/S6K axis, Cancer Prev. Res. (Phila), 6, 27, 10.1158/1940-6207.CAPR-12-0349

Selvaraj, 2016, Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway, Mol. Carcinog., 55, 818, 10.1002/mc.22324

Scarlatti, 2008, Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells, Cell Death Differ., 15, 1318, 10.1038/cdd.2008.51

Opipari, 2004, Resveratrol-induced autophagocytosis in ovarian cancer cells, Cancer Res., 64, 696, 10.1158/0008-5472.CAN-03-2404

Lang, F., Qin, Z., Li, F., Zhang, H., Fang, Z., and Hao, E. (2015). Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells. PLoS ONE, 10.

Chang, 2017, Resveratrol-induced autophagy and apoptosis in cisplatin-resistant human oral cancer CAR cells: A key role of AMPK and Akt/mTOR signaling, Int. J. Oncol., 50, 873, 10.3892/ijo.2017.3866

Zhang, 2013, Autophagic cell death induced by resveratrol depends on the Ca(2+)/AMPK/mTOR pathway in A549 cells, Biochem. Pharmacol., 86, 317, 10.1016/j.bcp.2013.05.003

Wang, 2018, Resveratrol, an activator of SIRT1, induces protective autophagy in non-small-cell lung cancer via inhibiting Akt/mTOR and activating p38-MAPK, Onco Targets Ther., 11, 7777, 10.2147/OTT.S159095

Zhang, 2014, The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells, Int. J. Mol. Med., 33, 987, 10.3892/ijmm.2014.1660

Adrian, 2000, Stilbene content of mature Vitis vinifera berries in response to UV-C elicitation, J. Agric. Food Chem., 48, 6103, 10.1021/jf0009910

Rimando, 2002, Cancer chemopreventive and antioxidant activities of pterostilbene, a naturally occurring analogue of resveratrol, J. Agric. Food Chem., 50, 3453, 10.1021/jf0116855

Chiou, 2010, Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice, J. Agric. Food Chem., 58, 8833, 10.1021/jf101571z

Chen, 2012, Chemopreventive effects of pterostilbene on urethane-induced lung carcinogenesis in mice via the inhibition of EGFR-mediated pathways and the induction of apoptosis and autophagy, J. Agric. Food Chem., 60, 11533, 10.1021/jf302778a

Pari, 2006, Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin- and nicotinamide-induced diabetic rats, Life Sci., 79, 641, 10.1016/j.lfs.2006.02.036

Jozwik, 2013, Pterostilbene induces accumulation of autophagic vacuoles followed by cell death in HL60 human leukemia cells, J. Physiol. Pharmacol., 64, 545

Ko, 2015, Pterostilbene induce autophagy on human oral cancer cells through modulation of Akt and mitogen-activated protein kinase pathway, Oral Oncol., 51, 593, 10.1016/j.oraloncology.2015.03.007

Yu, 2019, Inhibition of eIF2α dephosphorylation accelerates pterostilbene-induced cell death in human hepatocellular carcinoma cells in an ER stress and autophagy-dependent manner, Cell Death Dis., 10, 418, 10.1038/s41419-019-1639-5

Chen, 2010, Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells, Mol. Nutr. Food Res., 54, 1819, 10.1002/mnfr.201000067

Chakraborty, 2012, Long term induction by pterostilbene results in autophagy and cellular differentiation in MCF-7 cells via ROS dependent pathway, Mol. Cell. Endocrinol., 355, 25, 10.1016/j.mce.2012.01.009

Chang, 2018, Pterostilbene modulates the suppression of multidrug resistance protein 1 and triggers autophagic and apoptotic mechanisms in cisplatin-resistant human oral cancer CAR cells via AKT signaling, Int. J. Oncol., 52, 1504

Hsieh, 2014, A combination of pterostilbene with autophagy inhibitors exerts efficient apoptotic characteristics in both chemosensitive and chemoresistant lung cancer cells, Toxicol. Sci., 137, 65, 10.1093/toxsci/kft238

Verghese, 1993, Isolation of curcumin from Curcuma longa L. Rhizome, Flavour Fragr. J., 8, 315, 10.1002/ffj.2730080605

Goel, 2008, Curcumin as "Curecumin": from kitchen to clinic, Biochem. Pharmacol., 75, 787, 10.1016/j.bcp.2007.08.016

Daverey, 2016, Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes, Neuroscience, 333, 92, 10.1016/j.neuroscience.2016.07.012

Dhillon, 2008, Phase II trial of curcumin in patients with advanced pancreatic cancer, Clin. Cancer Res., 14, 4491, 10.1158/1078-0432.CCR-08-0024

Huang, 1991, Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis, Cancer Res., 51, 813

Giordano, A., and Tommonaro, G. (2019). Curcumin and Cancer. Nutrients, 11.

Jin, 2015, Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway, Oncol. Rep., 34, 2782, 10.3892/or.2015.4258

Xue, 2014, Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via regulation of mitochondrial signaling pathways, Asian Pac. J. Cancer Prev., 15, 3987, 10.7314/APJCP.2014.15.9.3987

Shehzad, 2013, Curcumin induces apoptosis in human colorectal carcinoma (HCT-15) cells by regulating expression of Prp4 and p53, Mol. Cells, 35, 526, 10.1007/s10059-013-0038-5

Li, 2004, Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis, Cancer, 101, 2351, 10.1002/cncr.20605

Liu, 2009, Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NF_B, cyclinD and MMP-1 transcription, Phytomedicine, 16, 916, 10.1016/j.phymed.2009.04.008

Mukhopadhyay, 2001, Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines, Oncogene, 20, 7597, 10.1038/sj.onc.1204997

Yang, C.W., Chang, C.L., Lee, H.C., Chi, C.W., Pan, J.P., and Yang, W.C. (2012). Curcumin induces the apoptosis of human monocytic leukemia THP-1 cells via the activation of JNK/ERK pathways. BMC Complement. Altern. Med., 12.

Han, 1999, Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53, Clin. Immunol., 93, 152, 10.1006/clim.1999.4769

Jia, 2009, Autophagic and apoptotic mechanisms of curcumin-induced death in K562 cells, J. Asian Nat. Prod. Res., 11, 918, 10.1080/10286020903264077

Zhao, 2016, Curcumin induces autophagy, inhibits proliferation and invasion by downregulating AKT/mTOR signaling pathway in human melanoma cells, Oncol. Rep., 35, 1065, 10.3892/or.2015.4413

Aoki, 2007, Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways, Mol. Pharmacol., 72, 29, 10.1124/mol.106.033167

Fu, 2018, Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling, J. Cell Physiol., 233, 4634, 10.1002/jcp.26190

Xiao, 2013, Curcumin induces autophagy via activating the AMPK signaling pathway in lung adenocarcinoma cells, J. Pharmacol. Sci., 123, 102, 10.1254/jphs.13085FP

Yang, 2017, Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation, Drug Des. Dev. Ther., 11, 431, 10.2147/DDDT.S126964

Berrak, 2015, Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells, Biomed. Pharmacother., 71, 161, 10.1016/j.biopha.2015.02.029

Lee, 2011, Involvement of ROS in Curcumin-induced Autophagic Cell Death, Korean J. Physiol. Pharmacol., 15, 1, 10.4196/kjpp.2011.15.1.1

Salvador, 2010, The dark side of curcumin, Int. J. Cancer, 126, 1771, 10.1002/ijc.24967

Sharma, 2004, Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance, Clin. Cancer Res., 10, 6847, 10.1158/1078-0432.CCR-04-0744

Cianfruglia, L., Minnelli, C., Laudadio, E., Scirè, A., and Armeni, T. (2019). Side Effects of Curcumin: Epigenetic and Antiproliferative Implications for Normal Dermal Fibroblast and Breast Cancer Cells. Antioxidants, 8.