Genistein As a Regulator of Signaling Pathways and MicroRNAs in Different Types of Cancers

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2021 Jul 22

PMID 34289845

Citations 24

Authors

Zeeshan Javed

Khushbukhat Khan

Jesus Herrera-Bravo

Sajid Naeem

Muhammad Javed Iqbal

Haleema Sadia

Qamar Raza Qadri

Shahid Raza

Asma Irshad

Ali Akbar

Zeljko Reiner

Ahmed Al-Harrasi

Ahmed Al-Rawahi

Dinara Satmbekova

Monica Butnariu

Iulia Cristina Bagiu

Radu Vasile Bagiu

Javad Sharifi-Rad

Affiliations

Soon will be listed here.

Abstract

Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

Citing Articles

Cellular and Molecular Mechanisms Modulated by Genistein in Cancer.

Naponelli V, Piscazzi A, Mangieri D Int J Mol Sci. 2025; 26(3).

PMID: 39940882 PMC: 11818640. DOI: 10.3390/ijms26031114.

Unleashing the potential of Genistein and its derivatives as effective therapeutic agents for breast cancer treatment.

Qaed E, Liu W, Almoiliqy M, Mohamed R, Tang Z Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39549063 DOI: 10.1007/s00210-024-03579-6.

Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy.

Gao R, Lin P, Yang W, Fang Z, Gao C, Cheng B Int J Nanomedicine. 2024; 19:10455-10478.

PMID: 39430311 PMC: 11491070. DOI: 10.2147/IJN.S479438.

Notch Signaling Suppression by Golden Phytochemicals: Potential for Cancer Therapy.

Zenjanab M, Hashemzadeh N, Alimohammadvand S, Sharifi-Azad M, Abdolahinia E, Jahanban-Esfahlan R Adv Pharm Bull. 2024; 14(2):302-313.

PMID: 39206407 PMC: 11347744. DOI: 10.34172/apb.2024.035.

Synergistic Mechanisms of Selected Polyphenols in Overcoming Chemoresistance and Enhancing Chemosensitivity in Colorectal Cancer.

Hon K, Naidu R Antioxidants (Basel). 2024; 13(7).

PMID: 39061884 PMC: 11273411. DOI: 10.3390/antiox13070815.

References

Dorling L, Carvalho S, Allen J, Gonzalez-Neira A, Luccarini C, Wahlstrom C . Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. N Engl J Med. 2021; 384(5):428-439. PMC: 7611105. DOI: 10.1056/NEJMoa1913948. View

Khongsti K, Das K, Das B . MAPK pathway and SIRT1 are involved in the down-regulation of secreted osteopontin expression by genistein in metastatic cancer cells. Life Sci. 2020; 265:118787. DOI: 10.1016/j.lfs.2020.118787. View

Tian J, Chi C, Bian G, Xing D, Guo F, Wang X . PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells. Colloids Surf B Biointerfaces. 2021; 203:111723. DOI: 10.1016/j.colsurfb.2021.111723. View

Mukund V . Genistein: Its Role in Breast Cancer Growth and Metastasis. Curr Drug Metab. 2020; 21(1):6-10. DOI: 10.2174/1389200221666200120121919. View

Gong L, Li Y, Nedeljkovic-Kurepa A, Sarkar F . Inactivation of NF-kappaB by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene. 2003; 22(30):4702-9. DOI: 10.1038/sj.onc.1206583. View

Li Y, Sarkar F . Inhibition of nuclear factor kappaB activation in PC3 cells by genistein is mediated via Akt signaling pathway. Clin Cancer Res. 2002; 8(7):2369-77. View

Pan H, Zhou W, He W, Liu X, Ding Q, Ling L . Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. Int J Mol Med. 2012; 30(2):337-43. DOI: 10.3892/ijmm.2012.990. View

Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar F . Inhibition of nuclear factor kappab activity by genistein is mediated via Notch-1 signaling pathway in pancreatic cancer cells. Int J Cancer. 2005; 118(8):1930-6. DOI: 10.1002/ijc.21589. View

10.

Al-Maghrebi M, Renno W . Genistein alleviates testicular ischemia and reperfusion injury-induced spermatogenic damage and oxidative stress by suppressing abnormal testicular matrix metalloproteinase system via the Notch 2/Jagged 1/Hes-1 and caspase-8 pathways. J Physiol Pharmacol. 2016; 67(1):129-37. View

11.

Dijsselbloem N, Goriely S, Albarani V, Gerlo S, Francoz S, Marine J . A critical role for p53 in the control of NF-kappaB-dependent gene expression in TLR4-stimulated dendritic cells exposed to Genistein. J Immunol. 2007; 178(8):5048-57. DOI: 10.4049/jimmunol.178.8.5048. View

12.

Kim E, Kwon K, Song M, Seo S, Park S, Ka S . Genistein protects pancreatic beta cells against cytokine-mediated toxicity. Mol Cell Endocrinol. 2007; 278(1-2):18-28. DOI: 10.1016/j.mce.2007.08.003. View

13.

Zhang H, Zhao Z, Pang X, Yang J, Yu H, Zhang Y . Genistein Protects Against Ox-LDL-Induced Inflammation Through MicroRNA-155/SOCS1-Mediated Repression of NF-ĸB Signaling Pathway in HUVECs. Inflammation. 2017; 40(4):1450-1459. DOI: 10.1007/s10753-017-0588-3. View

14.

Xu J, Xiong H, Zhao Z, Luo M, Ju Y, Yang G . Genistein suppresses allergic contact dermatitis through regulating the MAP2K2/ERK pathway. Food Funct. 2021; 12(10):4556-4569. DOI: 10.1039/d0fo03238g. View

15.

Malloy K, Wang J, Clark L, Fang Z, Sun W, Yin Y . Novasoy and genistein inhibit endometrial cancer cell proliferation through disruption of the AKT/mTOR and MAPK signaling pathways. Am J Transl Res. 2018; 10(3):784-795. PMC: 5883119. View

16.

Wang L, Li A, Liu Y, Zhan S, Zhong L, Du Y . Genistein protects against acetaminophen-induced liver toxicity through augmentation of SIRT1 with induction of Nrf2 signalling. Biochem Biophys Res Commun. 2020; 527(1):90-97. DOI: 10.1016/j.bbrc.2020.04.100. View

17.

Yi S, Chen S, Xiang J, Tan J, Huang K, Zhang H . Genistein exerts a cell-protective effect via Nrf2/HO-1/ /PI3K signaling in Ab25-35-induced Alzheimer's disease models in vitro. Folia Histochem Cytobiol. 2021; 59(1):49-56. DOI: 10.5603/FHC.a2021.0006. View

18.

Zhou C, Li D, Ding C, Yuan Q, Yu S, Du D . Involvement of SIRT1 in amelioration of schistosomiasis-induced hepatic fibrosis by genistein. Acta Trop. 2021; 220:105961. DOI: 10.1016/j.actatropica.2021.105961. View

19.

Zhang Y, Li Q, Chen H . DNA methylation and histone modifications of Wnt genes by genistein during colon cancer development. Carcinogenesis. 2013; 34(8):1756-63. PMC: 3731807. DOI: 10.1093/carcin/bgt129. View

20.

Zhang Y, Chen H . Genistein, an epigenome modifier during cancer prevention. Epigenetics. 2011; 6(7):888-91. DOI: 10.4161/epi.6.7.16315. View

21.

Wang Z, Chen H . Genistein increases gene expression by demethylation of WNT5a promoter in colon cancer cell line SW1116. Anticancer Res. 2010; 30(11):4537-45. View