Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation:A Systematic Review

Guilherme Vinício de Sousa Silva; Ana Luiza Vieira Ferreira Guimarães Lopes; Isis Carolina Viali; Lucas Zannini Medeiros Lima; Matheus Ribeiro Bizuti; Fabiana Brum Haag; Débora Tavares de Resende e Silva

doi:10.1007/s11655-022-3674-9

Your Location：

Home >

Browse articles >

Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation:A Systematic Review

Review | Updated：2023-02-22

- Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation:A Systematic Review
- Chinese Journal of Integrative Medicine Vol. 29, Issue 3, Pages: 268-279(2023)
- Affiliations：
  
  1.Department of Medicine, Federal University of Fronteira Sul, Chapecó, Santa Catarina, Brazil
  2.Department of Nursing, Federal University of Fronteira Sul, Chapecó, Santa Catarina, Brazil
  3.Department of Graduate Studies in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, Santa Catarina, Brazil
- Author bio：
  
  Dr. Débora Tavares de Resende e Silva, E-mail: debora.silva@uffs.edu.br
- Funds：
- DOI：10.1007/s11655-022-3674-9
  CLC：
- Published：2023-03，
  
  Published Online：09 July 2022，
  
  Accepted：02 March 2022
Scan for full text
Guilherme Vinício de Sousa Silva, Ana Luiza Vieira Ferreira Guimarães Lopes, Isis Carolina Viali, et al. Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation:A Systematic Review. [J]. Chinese Journal of Integrative Medicine 29(3):268-279(2023)
DOI：

Guilherme Vinício de Sousa Silva, Ana Luiza Vieira Ferreira Guimarães Lopes, Isis Carolina Viali, et al. Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation:A Systematic Review. [J]. Chinese Journal of Integrative Medicine 29(3):268-279(2023) DOI： 10.1007/s11655-022-3674-9.

摘要

Abstract

Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of carcinogenesis. Autophagy is a quality control system for proteins and plays a fundamental role in cancer carcinogenesis

exerting an anticarcinogenic role in normal cells and can inhibit the transformation of malignant cells. Therefore

drugs aimed at autophagy can function as antitumor agents. Flavonoids are a class of polyphenolic secondary metabolites commonly found in plants and

consequently

consumed in diets. In this review

the systematic search strategy was used

which included the search for descriptors "flavonoids" AND "mTOR pathway" AND "cancer" AND "autophagy"

in the electronic databases of PubMed

Cochrane Library

Web of Science and Scopus

from January 2011 to January 2021. The current literature demonstrates that flavonoids have anticarcinogenic properties

including inhibition of cell proliferation

induction of apoptosis

autophagy

necrosis

cell cycle arrest

senescence

impaired cell migration

invasion

tumor angiogenesis and reduced resistance to multiple drugs in tumor cells. We demonstrate the available evidence on the roles of flavonoids and autophagy in cancer progression and inhibition. (Registration No. CRD42021243071 at PROSPERO)

关键词

Keywords

anti-cancer effectsapoptosiscell proliferationcell survivalflavonoids

references

Prado BBF do. Influence of life habits on the development of cancer. Sci Cult (Portug) 2014;66:21-24.

Instituto Nacional de Câncer. What is cancer? Available at:https://www.inca.gov.br/o-que-e-cancerhttps://www.inca.gov.br/o-que-e-cancer. Accessed 13 Jun 2021.

Dos Santos DS, Farias Rodrigues MM. Pharmacological activities of flavonoids: a review study. UNIFAP Sci Stat(Portug) 2017;7:29.

Kabala-Dzik A, Rzepecka-Stojko A, Kubina R, et al. Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7—a comparative study. Cell Mol Biol 2018;64:1.

Gonçalves C, de Freitas M, Ferreira A. Flavonoids, thyroid iodide uptake and thyroid cancer—a review. Int J Mol Sci 2017;18:1247.

Ngabire D, Kim GD. Autophagy and inflammatory response in the tumor microenvironment. Int J Mol Sci 2017;18:2016.

Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. PLoS Med 2009;6:e1000097.

An HK, Kim KS, Lee JW, et al. Mimulone-induced autophagy through p53-mediated AMPK/mTOR pathway increases caspase-mediated apoptotic cell death in a549 human lung cancer cells. PLoS One 2014;9:e114607.

Dou J, Wang Z, Ma L, et al. Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence. Oncotarget 2018;9:20089-20102.

Wu X, Liu P, Zhang H, et al. Wogonin as a targeted therapeutic agent for EBV(+) lymphoma cells involved in LMP1/NF-κB/miR-155/PU.1 pathway. BMC Cancer 2017;17:147.

Jiang S, Chang H, Deng S, et al. Icariin enhances the chemosensitivity of cisplatin-resistant ovarian cancer cells by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway. Int J Oncol 2019;54:1933-1942.

Deng Y, Zhang Q, Li Y, et al. Pectolinarigenin inhibits cell viability, migration and invasion and induces apoptosis via a ROS-mitochondrial apoptotic pathway in melanoma cells. Oncol Lett 2020;20:116.

Cui XL, Li KJ, Ren HX, et al. Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-fluorouracil on gastric cancer cells through the AKT-mTOR pathway. World J Gastroenterol 2019;25:1854-1864.

Wang S, Yan Y, Cheng Z, et al. Sotetsu flavone suppresses invasion and metastasis in non-small-cell lung cancer A549 cells by reversing EMT via the TNF-α/NF-κB and PI3K/AKT signaling pathway. Cell Death Discov 2018;4:26.

Bonesi M, Loizzo MR, Menichini F, et al. Flavonoids in treating psoriasis. In: Immunity and inflammation in health and disease. Elsevier 2018;23:281-294.

Kashyap D, Sharma A, Sak K, et al. Fisetin: a bioactive phytochemical with potential for cancer prevention and pharmacotherapy. Life Sci 2018;194:75-87.

Bao HR, Chen JL, Li F, et al. Relationship between PI3K/mTOR/RhoA pathway-regulated cytoskeletal rearrangements and phagocytic capacity of macrophages. Braz J Med Biol Res 2020;53:e9207.

Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 2014;26:2694-2701.

Moon HI, Jeong MH, Jo WS. Protective activity of c-geranylflavonoid analogs from paulownia tomentosa against DNA damage in 137Cs irradiated AHH-1 cells. Natural Product Commun 2014;9:1295-1298.

Aryal P, Kim K, Park PH, et al. Baicalein induces autophagic cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human cancer cells. FEBS J 2014;281:4644-4658.

Liu H, Dong Y, Gao Y, et al. The fascinating effects of baicalein on cancer: a review. Int J Mol Sci 2016;17:1681.

Bie B, Sun J, Guo Y, et al. Baicalein: a review of its anti-cancer effects and mechanisms in hepatocellular carcinoma. Biomed Pharmacother 2017;93:1285-1291.

Hu J, Wang R, Liu Y, et al. Baicalein represses cervical cancer cell growth, cell cycle progression and promotes apoptosis via blocking AKT/mTOR pathway by the regulation of circHIAT1/miR-19a-3p axis. OncoTargets Ther 2021;14:905-916.

Ma XC, Yan W, Dai Z, et al. Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/beta-catenin pathway. Drug Des Devel Ther 2016;10:1419-1441.

Guo Z, Hu X, Xing Z, et al. Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/AKT/mTOR pathway. Mol Cell Biochem 2015;406:111-119.

Peng F, Du Q, Peng C, et al. A review: the pharmacology of isoliquiritigenin. Phytother Res 2015;29:969-977.

Zhao TT, Xu YQ, Hu HM, et al. Isoliquiritigenin and its formulations: potential antitumor agents. Curr Med Chem 2019;26:6786-6796.

Baba M, Asano R, Takigami I, et al. Studies on cancer chemoprevention by traditional folk medicines http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=40151956&type=http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=40151967&type=http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=40151961&type=. Inhibitory effect of isoliquiritigenin on azoxymethane-induced murine colon aberrant crypt focus formation and carcinogenesis. Biol Pharm Bull 2002;25:247-250.

Chen G, Hu X, Zhang W, et al. Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and apoptotic cell death in adenoid cystic carcinoma cells. Apoptosis 2012;17:90-101.

Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer. Mol Cancer 2020;19:12.

Patra S, Mishra SR, Behera BP, et al. Autophagy-modulating phytochemicals in cancer therapeutics: current evidences and future perspectives. Semin Cancer Biol 2022;80:205-217.

Khan NM, Haseeb A, Ansari MY, et al. Wogonin, a plant derived small molecule, exerts potent anti-inflammatory and chondroprotective effects through the activation of ROS/ERK/Nrf2 signaling pathways in human osteoarthritis chondrocytes. Free Radic Biol Med 2017;106:288-301.

Fu R, Chen Y, Wang XP, et al. Wogonin inhibits multiple myeloma-stimulated angiogenesis via c-Myc/VHL/HIF-1α signaling axis. Oncotarget 2016;7:5715-5727.

Chow S, Chen Y, Liang C, et al. Wogonin induces cross-regulation between autophagy and apoptosis via a variety of Akt pathway in human nasopharyngeal carcinoma cells. J Cell Biochem 2012;113:3476-3485.

He C, Wang Z, Shi J. Pharmacological effects of icariin. In:Advances in pharmacology. Elsevier 2020;87:179-203.

Cheng X, Tan S, Duan F, et al. Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM. Breast Cancer 2019;26:766-775.

Tian M, Yang S, Yan X. Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities. Braz J Med Biol Res 2018;51:e7151.

Huang S, Xie T, Liu W. Icariin inhibits the growth of human cervical cancer cells by inducing apoptosis and autophagy by targeting mTOR/PI3K/AKT signalling pathway. J BUON 2019;24:990-996.

Grynkiewicz G, Demchuk OM. New perspectives for fisetin. Front Chem 2019;7:697.

Jia S, Xu X, Zhou S, et al. Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress-and mitochondrial stress-dependent pathways. Cell Death Dis 2019;10:142.

Cheriet T, Ben-Bachir B, Thamri O, et al. Isolation and biological properties of the natural flavonoids pectolinarin and pectolinarigenin—a review. Antibiotics 2020;9:417.

Lee H, Venkatarame Gowda Saralamma V, Kim S, et al. Pectolinarigenin induced cell cycle arrest, autophagy, and apoptosis in gastric cancer cell via PI3K/AKT/mTOR signaling pathway. Nutrients 2018;10:1043.

Xu F, Gao X, Pan H. Pectolinarigenin inhibits non-small cell lung cancer progression by regulating the PTEN/PI3K/AKT signaling pathway. Oncol Rep 2018;40:3458-3468.

Zappavigna S, Vanacore D, Lama S, et al. Silybin-induced apoptosis occurs in parallel to the increase of ceramides synthesis and miRNAs secretion in human hepatocarcinoma cells. Int J Mol Sci 2019;20:2190.

Pignatelli P, Carnevale R, Menichelli D. Silybin and metabolic disorders. Intern Emerg Med 2019;14:1-3.

Li F, Ma Z, Guan Z, et al. Autophagy induction by silibinin positively contributes to its anti-metastatic capacity via AMPK/mTOR pathway in renal cell carcinoma. Int J Mol Sci 2015;16:8415-8429.

Boozari M, Hosseinzadeh H. Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phytother Res 2021;35:864-876.

Wang S, Xu X, Hu Y, et al. Sotetsuflavone induces autophagy in non-small cell lung cancer through blocking PI3K/Akt/mTOR signaling pathway in vivo and in vitro. Front Pharmacol 2019;10:1460.

An D, Song Z, Yi Y, et al. Oroxylin A, a methylated metabolite of baicalein, exhibits a stronger inhibitory effect than baicalein on the CYP1B1-mediated carcinogenic estradiol metabolite formation. Phytother Res 2019;33:1033-1043.

Zhao Y, Zhu Q, Bu X, et al. Triggering apoptosis by oroxylin A through caspase-8 activation and p62/SQSTM1 proteolysis. Redox Biol 2020;29:101392.

Zou M, Lu N, Hu C, et al. Beclin 1-mediated autophagy in hepatocellular carcinoma cells: implication in anticancer efficiency of oroxylin A via inhibition of mTOR signaling. Cell Signal 2012;24:1722-732.

Gourgiotis S, Kocher HM, Solaini L, et al. Gallbladder cancer. Am J Surg 2008;196:252-264.

Gupta A, Siddeek R, Gupta S, et al. Evaluation of platelet distribution width as novel biomarker in gall bladder cancer. J Carcinog 2020;19:5.

Torres O, Caldas L, Azevedo R, et al. Cholelithiasis and gallbladder carcinoma. Rev Col Bras Cir (Portug) 2002;29:88-91.

Jung K, Narwal M, Min S, et al . Squamous cell carcinoma of head and neck: what internists should know. Kor J Intern Med 2020;35:1031-1044.

Augustine D, Singh P, Rao R, et al. Role of cancer stem cells in head-and-neck squamous cell carcinoma—a systematic review. J Carcinog 2021;20:12.

Felippu A, Freire E, de Arruda Silva R, et al. Impact of delay in the diagnosis and treatment of head and neck cancer. Braz J Otorhinolaryngol 2016;82:140-143.

Nayyar A, Patil M, Lavanya T, et al. Serum ceruloplasmin as cancer marker in oral pre-cancers and cancers. J Carcinog 2021;20:15.

Kramer IR, Lucas RB, Pindborg JJ, et al. Definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46:518-539.

Krishna A, Singh S, Kumar V, et al. Molecular concept in human oral cancer. Natl J Maxillofac Surg 2015;6:9-15.

Câncer de boca. INCA—Instituto Nacional de Câncer. Available at: https://www.inca.gov.br/tipos-de-cancer/cancer-de-bocahttps://www.inca.gov.br/tipos-de-cancer/cancer-de-boca. Accessed 13 February, 2022.

de Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol 1966;28:435-492.

Galluzzi L, Bravo-San Pedro JM, Levine B, et al. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov 2017;16:487-511.

Amaravadi RK, Kimmelman AC, Debnath J. Targeting autophagy in cancer: recent advances and future directions. Cancer Discov 2019;9:1167-1181.

Eskelinen EL. The dual role of autophagy in cancer. Curr Opin Pharmacol 2011;11:294-300.

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. 4th ed. Autophagy 2021;17:1-382.

Zhou Y, Zheng J, Li Y, et al. Natural polyphenols for prevention and treatment of cancer. Nutrients 2016;8:515.

Sudhakaran M, Sardesai S, Doseff AI. Flavonoids: new frontier for immuno-regulation and breast cancer control. Antioxidants 2019;8:103.

Kopustinskiene DM, Jakstas V, Savickas A, et al. Flavonoids as anticancer agents. Nutrients 2020;12:457.

Aune D. Plant foods, antioxidant biomarkers, and the risk of cardiovascular disease, cancer, and mortality: a review of the evidence. Adv Nutr 2019;10:S404-S421.

Batra P, Sharma AK. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 2013;3:439-459.

Pang X, Zhang X, Jiang Y, et al. Autophagy: mechanisms and therapeutic potential of flavonoids in cancer. Biomolecules 2021;11:135.

Benvenuto M, Albonici L, Focaccetti C, et al. Polyphenol-mediated autophagy in cancer: evidence of in vitro and in vivo studies. Int J Mol Sci 2020;21:6635.

Kiruthiga C, Devi KP, Nabavi SM, et al. Autophagy: a potential therapeutic target of polyphenols in hepatocellular carcinoma. Cancers 2020;12:562.

Deng S, Shanmugam MK, Kumar AP, et al. Targeting autophagy using natural compounds for cancer prevention and therapy. Cancer 2019;125:1228-1246.

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

Flavonoid Myricetin as Potent Anticancer Agent:A Possibility towards Development of Potential Anticancer Nutraceuticals

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

Naringin Inhibits Colorectal Carcinogenesis by Inhibiting Viability of Colorectal Cancer Cells

Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis

Related Author

No data

Related Institution

Department of Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

Department of Critical Care Medicine, Changzhou Hospital of Traditional of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

Department of Biosciences, Faculty of Science, Integral University

Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University

Molecular Cell Biology Laboratory, Integral Information and Research Centre-4 (IIRC-4), Department of Bioengineering, Faculty of Engineering, Integral University

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰