Abstract
Cancer, a leading cause of global mortality, has been estimated to cause more deaths than all coronary heart disease or stroke. Mutation in the p53 gene is one of the major etiologies leading to carcinogenesis. p53 regarded as the “Guardian of the genome” regulates a large number of events including cell cycle arrest and apoptosis, among others. Treatment of cancer has mostly been confined to chemotherapy, radiotherapy, and surgery. However, these therapies can cause a severe threat to the life of the individual. Natural plant products have also been used due to their protective effect against various types of cancer. Quercetin, Luteolin, and Fisetin are polyphenolic compounds widely found in fruits and vegetables. They have been reported to possess antioxidant, anti-inflammatory, and antiproliferative properties among others. These properties make them a good candidate as an anticancer agent. Quercetin, Luteolin, and Fisetin have been shown to have a positive effect on the p53 expression. p53 shows potential in suppressing the expression of NF-κB, thereby repressing inflammation. Quercetin-, Luteolin-, and Fisetin-mediated stimulation of p53 causes arrest of cancerous cells at the various checkpoint of the cell cycle which further leads to apoptosis of cancerous cells. This section, therefore, discusses the anticancerous effect of quercetin, Luteolin, and Fisetin on the p53-mediated signaling in cancer.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, Büsselberg D (2019) Flavonoids in cancer and apoptosis. Cancers 11(1):28
Achanta G, Huang P (2004) Role of p53 in sensing oxidative DNA damage in response to reactive oxygen species-generating agents. Cancer Res 64(17):6233–6239
Afzal SM, Vafa A, Rashid S, Barnwal P, Shahid A, Shree A, Islam J, Ali N, Sultana S (2021) Protective effect of hesperidin against N, N′-dimethylhydrazine induced oxidative stress, inflammation, and apoptotic response in the colon of Wistar rats. Environ Toxicol 36(4):642–653
Bai L, Zhu W-G (2006) p53: structure, function and therapeutic applications. J Cancer Mol 2(4):141–153
Batra P, Sharma AK (2013) Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 3(6):439–459
Darband SG, Kaviani M, Yousefi B, Sadighparvar S, Pakdel FG, Attari JA, Mohebbi I, Naderi S, Majidinia M (2018) Quercetin: a functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer. J Cell Physiol 233(9):6544–6560
Fridman JS, Lowe SW (2003) Control of apoptosis by p53. Oncogene 22(56):9030–9040
George VC, Dellaire G, Rupasinghe HV (2017) Plant flavonoids in cancer chemoprevention: role in genome stability. J Nutr Biochem 45:1–14
Harris SL, Levine AJ (2005) The p53 pathway: positive and negative feedback loops. Oncogene 24(17):2899–2908
Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, Imran A, Orhan IE, Rizwan M, Atif M (2019) Luteolin, a flavonoid, as an anticancer agent: a review. Biomed Pharmacother 112:108612
Islam J, Shree A, Afzal SM, Vafa A, Sultana S (2020) Protective effect of Diosmin against benzo(a)pyrene-induced lung injury in Swiss Albino Mice. Environ Toxicol 35(7):747–757. https://doi.org/10.1002/tox.22909
Islam J, Shree A, Vafa A, Afzal SM, Sultana S (2021) Taxifolin ameliorates Benzo[a]pyrene-induced lung injury possibly via stimulating the Nrf2 signalling pathway. Int Immunopharmacol 96:107566. https://doi.org/10.1016/j.intimp.2021.107566
Joerger AC, Fersht AR (2016) The p53 pathway: origins, inactivation in cancer, and emerging therapeutic approaches. Annu Rev Biochem 85:375–404
Kashyap D, Garg VK, Tuli HS, Yerer MB, Sak K, Sharma AK, Kumar M, Aggarwal V, Sandhu SS (2019) Fisetin and quercetin: promising flavonoids with Chemopreventive potential. Biomol Ther 9(5):174
Khan H, Reale M, Ullah H, Sureda A, Tejada S, Wang Y, Zhang Z-J, Xiao J (2020) Anti-cancer effects of polyphenols via targeting p53 signaling pathway: updates and future directions. Biotechnol Adv 38:107385
Kim H-J, Kim S-K, Kim B-S, Lee S-H, Park Y-S, Park B-K, Kim S-J, Kim J, Choi C, Kim J-S (2010) Apoptotic effect of quercetin on HT-29 colon cancer cells via the AMPK signaling pathway. J Agric Food Chem 58(15):8643–8650
Li J, Cheng Y, Qu W, Sun Y, Wang Z, Wang H, Tian B (2011) Fisetin, a dietary flavonoid, induces cell cycle arrest and apoptosis through activation of p53 and inhibition of NF-kappa B pathways in bladder cancer cells. Basic Clin Pharmacol Toxicol 108(2):84–93
Li J, Qu W, Cheng Y, Sun Y, Jiang Y, Zou T, Wang Z, Xu Y, Zhao H (2014) The inhibitory effect of intravesical Fisetin against bladder cancer by induction of p53 and down-regulation of NF-kappa B pathways in a rat bladder carcinogenesis model. Basic Clin Pharmacol Toxicol 115(4):321–329
Li Y, Zhang T, Chen GY (2018) Flavonoids and colorectal cancer prevention. Antioxidants 7(12):187
Maurya AK, Vinayak M (2015) Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol Biol Rep 42(9):1419–1429
Naugler WE, Karin M (2008) NF-κB and cancer—identifying targets and mechanisms. Curr Opin Genet Dev 18(1):19–26
Panche A, Diwan A, Chandra S (2016) Flavonoids: an overview. J Nutr Sci 5:e47
Pandurangan AK, Esa NM (2014) Luteolin, a bioflavonoid inhibits colorectal cancer through modulation of multiple signaling pathways: a review. Asian Pac J Cancer Prev 15(14):5501–5508
Priyadarsini RV, Murugan RS, Maitreyi S, Ramalingam K, Karunagaran D, Nagini S (2010) The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur J Pharmacol 649(1–3):84–91
Schneider G, Krämer OH (2011) NFκB/p53 crosstalk—a promising new therapeutic target. Biochim Biophys Acta (BBA) Rev Cancer 1815(1):90–103
Sethi G, Sung B, Aggarwal BB (2008) Nuclear factor-κB activation: from bench to bedside. Exp Biol Med 233(1):21–31
Shree A, Hasan S, Islam J, Vafa A, Afzal S, Barnwal P, Siddiqi A, Ali R, Sultana S (2018) Colono-protective potentiality of Methanolic bark extract of Acacia catechu: a medicinal plant against 1, 2-Dimethylhydrazine-induced toxicity in Wistar rats. J Environ Pathol Toxicol Oncol 37(4):273–289
Shree A, Islam J, Vafa A, Mohammad Afzal S, Sultana S (2020) Gallic acid prevents 1, 2-Dimethylhydrazine induced colon inflammation, toxicity, mucin depletion, and goblet cell disintegration. Environ Toxicol 35(6):652–664. https://doi.org/10.1002/tox.22900
Shree A, Islam J, Sultana S (2021) Quercetin ameliorates reactive oxygen species generation, inflammation, mucus depletion, goblet disintegration, and tumor multiplicity in colon cancer: probable role of adenomatous polyposis coli, β-catenin. Phytother Res 35(4):2171–2184. https://doi.org/10.1002/ptr.6969
Tergaonkar V, Perkins ND (2007) p53 and NF-κB crosstalk: IKKα tips the balance. Mol Cell 26(2):158–159
Tergaonkar V, Pando M, Vafa O, Wahl G, Verma I (2002) p53 stabilization is decreased upon NFκB activation: a role for NFκB in acquisition of resistance to chemotherapy. Cancer Cell 1(5):493–503
Toufektchan E, Toledo F (2018) The guardian of the genome revisited: p53 downregulates genes required for telomere maintenance, DNA repair, and centromere structure. Cancers 10(5):135
Vafa A, Afzal S, Barnwal P, Rashid S, Shahid A, Alpashree, Islam J, Sultana S (2020) Protective role of diosmin against testosterone propionate-induced prostatic hyperplasia in Wistar rats: plausible role of oxidative stress and inflammation. Hum Exp Toxicol 39(9):1133–1146
Vousden KH, Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8(4):275–283
Zhao Y, Hu X, Zuo X, Wang M (2018) Chemopreventive effects of some popular phytochemicals on human colon cancer: a review. Food Funct 9(9):4548–4568
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2022 Springer Nature Singapore Pte Ltd.
About this entry
Cite this entry
Islam, J. (2022). Protective Effect of Quercetin, Luteolin, and Fisetin via Stimulating the p53-Mediated Signaling in Cancer. In: Chakraborti, S. (eds) Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-16-5422-0_20
Download citation
DOI: https://doi.org/10.1007/978-981-16-5422-0_20
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-5421-3
Online ISBN: 978-981-16-5422-0
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences