Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery


ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

Apigenin, A Plant Flavone Playing Noble Roles in Cancer Prevention Via Modulation of Key Cell Signaling Networks

Author(s): Deepti Singh, Mohammad A. Khan and Hifzur R. Siddique*

Volume 14, Issue 4, 2019

Page: [298 - 311] Pages: 14

DOI: 10.2174/1574892814666191026095728

Price: $65


Background: Cancer is a global health problem and the continuous rise in incidence and mortality due to cancer carries a real economic burden to all countries. Accumulation of genetic mutation, exposure of environmental carcinogens and food habits due to change in lifestyles are the key reasons for cancer. Targeting cancer cells, we need a multitargeting molecule with low/no toxicity.

Objective: To review the current update of the research status of chemopreventive/therapeutic molecule, Apigenin.

Methods: Compare the results of the published articles and granted patents on this compound. We also discuss the pros and cons of the present research and future direction.

Results: Cancer cells have characteristic alterations and dysregulation of various cell signaling pathways that control cell homeostasis, proliferation, motility, and survival in normal cells. Natural flavonoids are the compounds well known for their anti-inflammatory, anti-oxidant, and anti-cancerous properties. Apigenin, along with several other physiological effects, has a very low intrinsic toxicity and striking effects on the proliferation of cancer cells. Interestingly, this multitargeting molecule is getting wide acceptance among researchers. It is evident from the recent patents filed in this compound. At present, three patents have been granted only on the anticancer properties of apigenin.

Conclusion: This mini-review will explain the present research status of apigenin and will further shine some light on how apigenin performs its anti-cancerous actions by interfering with the key cellsignaling pathways.

Keywords: Apigenin, bioavailability, cancer, cell signaling, chemoresistance, patents, prevention, therapy.

Mishra AP, Salehi B, Sharifi-Rad M, Pezzani R, Kobarfard F, Sharifi-Rad J, et al. Programmed cell death, from a cancer perspective: An overview. Mol Diagn Ther 2018; 22(3): 281-95.
[] [PMID: 29560608]
Sankaranarayanan R, Ramadas K, Qiao YL. Managing the changing burden of cancer in Asia. BMC Med 2014; 12: 3.
[] [PMID: 24400922]
Blackadar CB. Historical review of the causes of cancer. World J Clin Oncol 2016; 7(1): 54-86.
[] [PMID: 26862491]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011; 144(5): 646-74.
[] [PMID: 21376230]
Siddique HR, Saleem M. Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: Preclinical and clinical evidences. Stem Cells 2012; 30(3): 372-8.
[] [PMID: 22252887]
Siddique HR, Feldman DE, Chen CL, Punj V, Tokumitsu H, Machida K. NUMB phosphorylation destabilizes p53 and promotes self-renewal of tumor-initiating cells by a NANOG-dependent mechanism in liver cancer. Hepatology 2015; 62(5): 1466-79.
[] [PMID: 26174965]
Arjmand F, Afsan Z, Sharma S, Parveen S, Yousuf I, Sartaj S, et al. Recent advances in metalodrug-like molecules targetting non-coding RNAs (ncRNAs) in cancer chemotherapy. Coord Chem Rev 2019; 387: 47-59.
Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harb Perspect Med 2015; 5(4)a006098
[] [PMID: 25833940]
Kumar S, Pandey AK. Chemistry and biological activities of Flavonoids: An overview. The Sci World J 2013 2013. Article ID162750
Salehi B, Fokou PVT, Sharifi-Rad M, Zucca P, Pezzani R, Martins N, et al. The therapeutic potential of naringenin: A review of clinical trials. Pharmaceuticals (Basel) 2019; 12(1)E11
[] [PMID: 30634637]
Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, et al. The therapeutic potential of apigenin. Int J Mol Sci 2019; 20(6)E1305
[] [PMID: 30875872]
Batra P, Sharma AK. Anti-cancer potential of flavonoids: Recent trends and future perspectives. 3 Biotech 2013; 3(6): 439-59.
[] [PMID: 28324424]
Leopoidin M, Pitarch IP, Russo N, Toscano M. Structure, conformation, and electronic properties of apigenin, luteolin and taxifolin antioxidants. A First principle theoretical study. J Phys Chem A 2004; 108(1): 92-6.
Gradolatto A, Basly JP, Berges R, Teyssier C, Chagnon MC, Siess MH, et al. Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metab Dispos 2005; 33(1): 49-54.
[] [PMID: 15466493]
Gupta S, Afaq F, Mukhtar H. Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. Biochem and Biophys Res Commun 2001; 287: 914-20.
Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 52(4): 673-751.
[PMID: 11121513]
Singh P, Mishra SK, Noel S, Sharma S, Rath SK. Acute exposure of apigenin induces hepatotoxicity in Swiss mice. PLoS One 2012; 7(2)e31964
[] [PMID: 22359648]
Shukla S, Bhaskaran N, Babcook MA, Fu P, Maclennan GT, Gupta S. Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway. Carcinogenesis 2014; 35(2): 452-60.
[] [PMID: 24067903]
Silvan S, Manoharan S, Baskaran N, Karthikeyan S, Prabhakar MM. Protective effect of apigenin on 7, 12-Dimethybenz(A) anthracene induced glycoconjugates in the plasma and buccal mucosa of golden Syrian hamsters. Int J Pharm Sci Res 2011; 1753-8.
Tatsuta A, Iishi H, Baba M, Yano H, Murata K, Mukai M, et al. Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats. Clin Exp Metastasis 2000; 18(8): 657-62.
[] [PMID: 11827069]
Zhong Y, Krisanapun C, Lee SH, Nualsanit T, Sams C, Peungvicha P, et al. Molecular targets of apigenin in colorectal cancer cells: Involvement of p21, NAG-1 and p53. Eur J Cancer 2010; 46(18): 3365-74.
[] [PMID: 20709524]
Shukla S, Gupta S. Molecular targets for apigenin-induced cell cycle arrest and apoptosis in prostate cancer cell xenograft. Mol Cancer Ther 2006; 5(4): 843-52.
[] [PMID: 16648554]
Budhraja A, Gao N, Zhang Z, Son YO, Cheng S, Wang X, et al. Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. Mol Cancer Ther 2012; 11(1): 132-42.
[] [PMID: 22084167]
Masuelli L, Benvenuto M, Mattera R, Di Stefano E, Zago E, Taffera G, et al. In vitro and in vivo anti-tumoral effects of the flavonoid apigenin in malignant mesothelioma. Front Pharmacol 2017; 8: 373.
Seo HS, Jo JK, Ku JM, Choi HS, Choi YK, Woo JK, et al. Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells. Biosci Rep 2015; 35(6) e00276
[] [PMID: 26500281]
Zhu J, Cai Y, Xu K, Ren X, Sun J, Lu S, et al. Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy-dependent pathway in human synovial sarcoma cells. Oncol Rep 2018; 40(4): 1927-36.
[] [PMID: 30066884]
Zeng X, Huang H, Tamai K, Zhang X, Harada Y, Yokota C, et al. Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions. Development 2008; 135(2): 367-75.
[] [PMID: 18077588]
Lee Y, Sung B, Kang YJ, Kim DH, Jang JY, Hwang SY, et al. Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells. Int J Oncol 2014; 44(5): 1599-606.
[] [PMID: 24626522]
Maggioni D, Garavello W, Rigolio R, Pignataro L, Gaini R, Nicolini G. Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. Int J Oncol 2013; 43(5): 1675-82.
[] [PMID: 23969487]
Zhang L, Cheng X, Gao Y, Zheng J, Xu Q, Sun Y, et al. Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells. Food Funct 2015; 6(11): 3464-72.
[] [PMID: 26292725]
Pham H, Chen M, Takahashi H, King J, Reber HA, Hines OJ, et al. Apigenin inhibits NNK-induced focal adhesion kinase activation in pancreatic cancer cells. Pancreas 2012; 41(8): 1306-15.
[] [PMID: 22889981]
Kim EY, Kim AK. Apigenin sensitizes Huh-7 human hepatocellular carcinoma cells to TRAIL-induced apoptosis. Biomol Ther (Seoul) 2012; 20(1): 62-7.
[] [PMID: 24116276]
D’Arcy MS. Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int 2019; 43(6): 582-92.
[] [PMID: 30958602]
Shukla S, Fu P, Gupta S. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer. Apoptosis 2014; 19(5): 883-94.
[] [PMID: 24563225]
Wang IK, Lin-Shiau SY, Lin JK. Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur J Cancer 1999; 35(10): 1517-25.
[] [PMID: 10673981]
Abu-Yousif AO, Smith KA, Getsios S, Green KJ, Van Dross RT, Pelling JC. Enhancement of UVB-induced apoptosis by apigenin in human keratinocytes and organotypic keratinocyte cultures. Cancer Res 2008; 68(8): 3057-65.
[] [PMID: 18413777]
Gupta S, Afaq F, Mukhtar H. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene 2002; 21(23): 3727-38.
[] [PMID: 12032841]
Baddani M. Autophagy mechanism, regulation, functions and disorder. ISRN Cell Biology (Basel) 2012; 2012 Article ID:927064
Fulda S. Autophagy in cancer therapy. Front Oncol 2017; 7: 128.
[] [PMID: 28674677]
Gaballah HH, Gaber RA, Mohamed DA. Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms. Toxicol Appl Pharmacol 2017; 316: 27-35.
[] [PMID: 28025107]
Wang Q, Zeng P, Liu Y, Wen G, Fu X, Sun X. Inhibition of autophagy ameliorates atherogenic inflammation by augmenting apigenin-induced macrophage apoptosis. Int Immunopharmacol 2015; 27(1): 24-31.
[] [PMID: 25899084]
Ruela-de-Sousa RR, Fuhler GM, Blom N, Ferreira CV, Aoyama H, Peppelenbosch MP. Cytotoxicity of apigenin on leukemia cell lines: Implications for prevention and therapy. Cell Death Dis 2010; 1(1) e19
[] [PMID: 21364620]
Tong X, Smith KA, Pelling JC. Apigenin, a chemopreventive bioflavonoid, induces AMP-activated protein kinase activation in human keratinocytes. Mol Carcinog 2012; 51(3): 268-79.
[] [PMID: 21538580]
Cao X, Liu B, Cao W, Zhang W, Zhang F, Zhao H, et al. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells. Chin J Cancer Res 2013; 25(2): 212-22.
[PMID: 23592903]
Yang J, Pi C, Wang G. Inhibition of PI3K/Akt/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells. Biomed Pharmacother 2018; 103: 699-707.
Coelho PL, Oliveira MN, da Silva AB, Pitanga BP, Silva VD, Faria GP, et al. The flavonoid apigenin from Croton betulaster Mull inhibits proliferation, induces differentiation and regulates the inflammatory profile of glioma cells. Anticancer Drugs 2016; 27(10): 960-9.
[] [PMID: 27622606]
Zhu Y, Wu J, Li S, Wang X, Liang Z, Xu X, et al. Apigenin inhibits migration and invasion via modulation of epithelial mesenchymal transition in prostate cancer. Mol Med Rep 2015; 11(2): 1004-8.
[] [PMID: 25351792]
Hu XW, Meng D, Fang J. Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase. Carcinogenesis 2008; 29(12): 2369-76.
[] [PMID: 18974065]
Chunhua L, Donglan L, Xiuqiong F, Lihua Z, Qin F, Yawei L, et al. Apigenin up-regulates transgelin and inhibits invasion and migration of colorectal cancer through decreased phosphorylation of AKT. J Nutr Biochem 2013; 24(10): 1766-75.
[] [PMID: 23773626]
Zhao G, Han X, Cheng W, Ni J, Zhang Y, Lin J, et al. Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells. Oncol Rep 2017; 37(4): 2277-85.
[] [PMID: 28260058]
Dai J, Van Wie PG, Fai LY, Kim D, Wang L, Poyil P, et al. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells. Toxicol Appl Pharmacol 2016; 311: 106-12.
[] [PMID: 27664007]
Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002; 296(5573): 1655-7.
[] [PMID: 12040186]
Cheung M, Testa JR. Diverse mechanisms of AKT pathway activation in human malignancy. Curr Cancer Drug Targets 2013; 13(3): 234-44.
[] [PMID: 23297823]
Willems L, Tamburini J, Chapuis N, Lacombe C, Mayeux P, Bouscary D. PI3K and mTOR signaling pathways in cancer: New data on targeted therapies. Curr Oncol Rep 2012; 14(2): 129-38.
[] [PMID: 22350330]
Tong X, Pelling JC. Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anticancer Agents Med Chem 2013; 13(7): 971-8.
[] [PMID: 23272913]
Kaur P, Shukla S, Gupta S. Plant flavonoid apigenin inactivates Akt to trigger apoptosis in human prostate cancer: An in vitro and in vivo study. Carcinogenesis 2008; 29(11): 2210-7.
[] [PMID: 18725386]
Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: Anti-cancer effects and mechanisms of action. Cell Biosci 2017; 7: 50.
[] [PMID: 29034071]
Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115(5): 577-90.
[] [PMID: 14651849]
Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, et al. AMPK phosphorylation of Raptor mediates a metabolic checkpoint. Mol Cell 2008; 30(2): 214-26.
[] [PMID: 18439900]
Constantinescu SN, Girardot M, Pecquet C. Mining for JAK-STAT mutations in cancer. Trends Biochem Sci 2008; 33(3): 122-31.
[] [PMID: 18291658]
Schwaller J. Modeling ETV6-JAK2-induced leukemia: Insights from the zebrafish. Haematologica 2012; 97(12): 1783-5.
[] [PMID: 23204479]
Warsch W, Walz C, Sexl V. JAK of all trades: JAK2-STAT5 as novel therapeutic targets in BCR-ABL1+ chronic myeloid leukemia. Blood 2013; 122(13): 2167-75.
[] [PMID: 23926299]
Morales JK, Falanga YT, Depcrynski A, Fernando J, Ryan JJ. Mast cell homeostasis and the JAK-STAT pathway. Genes Immun 2010; 11(8): 599-608.
[] [PMID: 20535135]
Villarino AV, Kanno Y, Ferdinand JR, O’Shea JJ. Mechanisms of Jak/STAT signaling in immunity and disease. J Immunol 2015; 194(1): 21-7.
[] [PMID: 25527793]
Cao HH, Chu JH, Kwan HY, Su T, Yu H, Cheng CY, et al. Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma. Sci Rep 2016; 6: 21731.
[] [PMID: 26911838]
Seo HS, Ku JM, Choi HS, Woo JK, Jang BH, Go H, et al. Apigenin induces caspase-dependent apoptosis by inhibiting signal transducer and activator of transcription 3 signaling in HER2-overexpressing SKBR3 breast cancer cells. Mol Med Rep 2015; 12(2): 2977-84.
[] [PMID: 25936427]
Suh YA, Jo SY, Lee HY, Lee C. Inhibition of IL-6/STAT3 axis and targeting Axl and Tyro3 receptor tyrosine kinases by apigenin circumvent taxol resistance in ovarian cancer cells. Int J Oncol 2015; 46(3): 1405-11.
[] [PMID: 25544427]
Komiya Y, Habas R. Wnt signal transduction pathways. Organogenesis 2008; 4(2): 68-75.
[] [PMID: 19279717]
Abrahamsson AE, Geron I, Gotlib J, Dao KH, Barroga C1F, Newton IG, et al. Glycogen synthase kinase 3β missplicing contributes to leukemia stem cell generation. Proc Natl Acad Sci USA 2009; 106(10): 3925-9.
[] [PMID: 19237556]
Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, et al. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004; 74(5): 1043-50.
[] [PMID: 15042511]
Galy O, Chemin I, Le Roux E, Villar S, Le Calvez-Kelm F, Lereau M, et al. Mutations in TP53 and CTNNB1 in relation to hepatitis B and C infections in hepatocellular carcinomas from Thailand. Hepat Res Treat 2011; 2011697162
[] [PMID: 21760996]
Björklund P, Akerström G, Westin G. An LRP5 receptor with internal deletion in hyperparathyroid tumors with implications for deregulated WNT/beta-catenin signaling. PLoS Med 2007; 4(11) e328
[] [PMID: 18044981]
Oikonomou E, Barreto DC, Soares B, De Marco L, Buchfelder M, Adams EF. Beta-catenin mutations in craniopharyngiomas and pituitary adenomas. J Neurooncol 2005; 73(3): 205-9.
[] [PMID: 15980970]
Novellasdemunt L, Antas P, Li VS. Targeting Wnt signaling in colorectal cancer. A review in the theme: Cell signalling: Proteins, pathways, mechanisms. Am J Physiol Cell Physiol 2015; 309(8): C511-21.
[] [PMID: 26289750]
Lin CM, Chen HH, Lin CA, Wu HC, Sheu JJ, Chen HJ. Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling. Sci Rep 2017; 7(1): 372.
[] [PMID: 28337019]
Xu M, Wang S, Song YU, Yao J, Huang K, Zhu X. Apigenin suppresses colorectal cancer cell proliferation, migration and invasion via inhibition of the Wnt/β-catenin signaling pathway. Oncol Lett 2016; 11(5): 3075-80.
[] [PMID: 27123066]
Shukla S, MacLennan GT, Flask CA, Fu P, Mishra A, Resnick MI, et al. Blockade of β-catenin signaling by plant flavonoid apigenin suppresses prostate carcinogenesis in TRAMP mice. Cancer Res 2007; 67(14): 6925-35.
[] [PMID: 17638904]
Keshet Y, Seger R. The MAP kinase signaling cascades: A system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 2010; 661: 3-38.
[] [PMID: 20811974]
Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 2002; 12(1): 9-18.
[] [PMID: 11942415]
Yang S, Liu G. Targeting the Ras/Raf/MEK/ERK pathway in hepatocellular carcinoma. Oncol Lett 2017; 13(3): 1041-7.
[] [PMID: 28454211]
De Luca A, Maiello MR, D’Alessio A, Pergameno M, Normanno N. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets 2012; 16(16)(Suppl. 2): S17-27.
[] [PMID: 22443084]
Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene 2007; 26(22): 3279-90.
[] [PMID: 17496922]
Chen M, Wang X, Zha D, Cai F, Zhang W, He Y, et al. Apigenin potentiates TRAIL therapy of non-small cell lung cancer via upregulating DR4/DR5 expression in a p53-dependent manner. Sci Rep 2016; 6: 35468.
[] [PMID: 27752089]
Shao H, Jing K, Mahmoud E, Huang H, Fang X, Yu C. Apigenin sensitizes colon cancer cells to antitumor activity of ABT-263. Mol Cancer Ther 2013; 12(12): 2640-50.
[] [PMID: 24126433]
Shukla S, MacLennan GT, Fu P, Gupta S. Apigenin attenuates insulin-like growth factor-I signaling in an autochthonous mouse prostate cancer model. Pharm Res 2012; 29(6): 1506-17.
[] [PMID: 22139534]
Hasnat MA, Pervin M, Lim JH, Lim BO. Apigenin attenuates melanoma cell migration by inducing anoikis through integrin and focal adhesion kinase inhibition. Molecules 2015; 20(12): 21157-66.
[] [PMID: 26633318]
Shukla S, Gupta S. Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle 2007; 6(9): 1102-14.
[] [PMID: 17457054]
Lim W, Park S, Bazer FW, Song G. Apigenin reduces survival of choriocarcinoma cells by inducing apoptosis via the PI3K/AKT and ERK1/2 MAPK pathways. J Cell Physiol 2016; 231(12): 2690-9.
[] [PMID: 26970256]
Gutierrez-Uribe JA, Serna-Saldivar SRO, Moreno-Cuevas JE, Hernandez-Brenes C, Guajardo-Touche EM. Cancer cell growth inhibition by black bean (Phaseolus vulgaris L) extracts US7763292. (2010).
Uckun FM. EGF-Genistein conjugates for the treatment of cancer US5911995. (1999).
Wen-zhe MA. Use of nobiletin in cancer treatment US9808477. (2017).
Young C. Methods and compositions for inhibiting the proliferation of prostate cancer cells US6680342. (2004).
Walle T. A method of treating colon cancer by administering apigenin, luteolin, diosmetin and chrysin WO2001058410. (2001).
Liu Y. A kind of chrysin phenylalanine derivative with anti-lung cancer activity CN109824642. (2019).
Mukhtar H, Khan N, Mohammad A, Afaq F. Methods of treating androgen dependent prostate cancer by administering an active pharmaceutical ingredient being fisetin, 3,3',4',7-tetrahydroxyflavone or a derivative thereof, in an oral, transdermal or topical dosage form US20100010078. (2010).
Young SS. Use in anti-cancer agent of 4'-o-glucose-luteolin KR20100134966. (2010).
Nakajima N, Kawashima N. Cancer proliferation inhibitor JP2012025724. (2012).
Vorsa N, Vvedenskaya IO, Huang M-T, Rosen LRSL. Antiinflammatory cranberry flavonol extract preparations US7270837. (2007).
Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: Promising natural compounds against viral infections. Arch Virol 2017; 162(9): 2539-51.
[] [PMID: 28547385]
Yuen K. Baicalin and its derivatives as a treatment for SARS corona virus infection or other related infections WO2005044291. (2005).
Hwa-Jeong C. Flavonoid comprising anti-virus activity KR101334348. (2013).
Kim JW, Han JJ, Park EY, et al. Genistein derivatives and anti-fungal composition containing the same WO2007061254. (2007).
Yuan J. Application of kaempferol as synergist of anti-fungal medicaments CN102218052. (2012).
Kim C. Pharmaceutical compositions for preventing or treating lung cancer comprising apigenin, curcumin, and honokiol as active ingredients KR101803000. (2017).
Yang C. Applications of apigenin for preparation of medicines inhibiting liver cancer epithelial-mesenchymal transition CN106377522. (2017).
Kim BB. Method for improving anti-cancer effect of apigenin by irradiation and pharmaceutical composition for treating or preventing cancer comprising irradiated apigenin KR20160132185. (2016).
Song KH. Pharmaceutical composition for preventing or treating choriocarcinoma comprising apigenin, chrysophanol or mixture thereof KR20180132212. (2018).
Jiang BH. Apigenin for chemoprevention, and chemotherapy combined with therapeutic reagents US8377918. (2013).
Liu Y. Safe natural pharmaceutical composition for treating cancer US20040072790. (2004).
Cohen I. Methods and compositions for the treatment of cancer AU2009289644. (2010).
Lei Z. Pharmaceutical composition having apigenin and apigenin derivative as well as histone deacetylase inhibitors and application thereof CN102441167. (2014).
He B, You L, Xu Z, Jablons DM. Methods for treating cancer by inhibiting Wnt signaling US20090304695. (2009).
Hollman PC, Katan MB. Health effects and bioavailability of dietary flavonols. Free Radic Res 1999; 31: S75-80.
[] [PMID: 10694044]
Ross JA, Kasum CM. Dietary flavonoids: Bioavailability, metabolic effects, and safety. Annu Rev Nutr 2002; 22: 19-34.
[] [PMID: 12055336]
Walle UK, Walle T. Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements. Drug Metab Dispos 2002; 30(5): 564-9.
[] [PMID: 11950788]
Ding B, Chen H, Wang C, Zhai Y, Zhai G. Preparation and in vitro evaluation of apigenin loaded lipid nanocapsules. J Nanosci Nanotechnol 2013; 13(10): 6546-52.
[] [PMID: 24245113]
Cochran DB, Gray LN, Anderson KW, Dziubla TD. Degradable poly(apigenin) polymer inhibits tumor cell adhesion to vascular endothelial cells. J Biomed Mater Res B Appl Biomater 2016; 104(7): 1438-47.
[] [PMID: 26251070]
Rajendran I, Dhandapani H, Anantharaman R, Rajaram R. Apigenin mediated gold nanoparticle synthesis and their anti-cancer effect on human epidermoid carcinoma (A431) cells. RSC Advances 2015; 5: 51055-66.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy