Advanced search
Publication Cover
International Journal of Food Properties Volume 26, 2023 - Issue 2
Submit an article Journal homepage
1,176
Views
0
CrossRef citations to date
0
Altmetric
Review Article

Anticancer perspectives of genistein: a comprehensive review

Hammad Naeema Department of Food Science and Technology, Muhammad Nawaz Shareef University of Agriculture Multan, Pakistan
,
Ushna Momala Department of Food Science and Technology, Muhammad Nawaz Shareef University of Agriculture Multan, Pakistan
,
Muhammad Imranb Department of food science and technology, University of Narowal-Pakistan, Narowal
,
Muhammad Shahbaza Department of Food Science and Technology, Muhammad Nawaz Shareef University of Agriculture Multan, Pakistan
,
Muzzamal Hussainc Department of Food Sciences, Government College University Faisalabad, Faisalabad, PakistanORCID Iconhttps://orcid.org/0000-0001-6508-1962
ORCID Icon,
Suliman A. Alsagabyd Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, AL-Majmaah, Saudi Arabia
,
Waleed Al Abdulmoneme Department of Pathology, College of Medicine, Qassim University, Buraidah, Kingdom of Saudi Arabia
,
Maryam Umarc Department of Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan
,
Ahmad Mujtabaf Department of Food Sciences and Technology, Faculty of Engineering and Technology, Hamdard UniversityIslamabad Campus, Pakistan
,
Ahmed H. El-Ghorabg Department of Chemistry, College of Science, Jouf University, Sakaka, Saudi Arabia
,
Mohammed M. Ghoneimh Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia;i Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
,
Mohamed E. Shakerj Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf, Saudi Arabia;k Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
,
Mohamed A. Abdelgawadl Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia;m Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-suef, Egypt
&
Entessar AL JBawin Agricultural Extension Directorate, MAAR, Damascus, SyriaCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-1804-1770
ORCID Icon show all
Pages 3305-3341 | Received 11 Aug 2023, Accepted 03 Nov 2023, Published online: 27 Nov 2023

References

  • Rasheed, S.; Rehman, K.; Shahid, M.; Suhail, S.; Akash, M. S. Therapeutic Potentials of Genistein: New Insights and Perspectives. J. Food Biochem. 2022, 46(9), e14228. DOI: 10.1111/jfbc.14228.
  • Tuli, H. S.; Tuorkey, M. J.; Thakral, F.; Sak, K.; Kumar, M.; Sharma, A. K.; Sharma, U.; Jain, A.; Aggarwal, V.; Bishayee, A. Molecular Mechanisms of Action of Genistein in Cancer: Recent Advances. Front. Pharmacol. 2019, 10, 1336. DOI: 10.3389/fphar.2019.01336.
  • Yang, Z.; Kulkarni, K.; Zhu, W.; Hu, M. Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on Its ADME. Anti-Cancer Agents Med. Chem. (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2012, 12(10), 1264–1280. DOI: 10.2174/187152012803833107.
  • Sethi, G.; Rath, P.; Chauhan, A.; Ranjan, A.; Choudhary, R.; Ramniwas, S.; Sak, K.; Aggarwal, D.; Rani, I.; Tuli, H. S. Apoptotic Mechanisms of Quercetin in Liver Cancer: Recent Trends and Advancements. Pharmaceutics. 2023, 15(2), 712. DOI: 10.3390/pharmaceutics15020712.
  • Pawlicka, M. A.; Zmorzyński, S.; Popek-Marciniec, S.; Filip, A. A. The Effects of Genistein at Different Concentrations on MCF-7 Breast Cancer Cells and BJ Dermal Fibroblasts. Int. J. Mol. Sci. 2022, 23(20), 12360. DOI: 10.3390/ijms232012360.
  • Hu, C.; Wang, M.; Hu, M.; Ma, S.; Yang, B.; Xiao, W.; Zhou, Q.; Zhou, M.; Li, Z. Genistein Induces Endocrine Resistance in Human Breast Cancer by Suppressing H3K27 Trimethylation. Endocr. Relat. Cancer. 2023, 30(2), e220191. DOI: 10.1530/ERC-22-0191.
  • Mukund, V. G. Genistein: Its Role in Breast Cancer Growth and Metastasis. Curr. Drug Metab. 2020, 21(1), 6–10. DOI: 10.2174/1389200221666200120121919.
  • Chen, B.; Wu, L.; Tang, X.; Wang, T.; Wang, S.; Yu, H.; Wan, G.; Xie, M.; Zhang, R.; Xiao, H., et al. Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990. Front Pharmacol. 2022, 13, 874696. DOI: 10.3389/fphar.2022.874696.
  • Malik, P.; Singh, R.; Kumar, M.; Malik, A.; Mukherjee, T. K. Understanding the Phytoestrogen Genistein Actions on Breast Cancer: Insights on Estrogen Receptor Equivalence, Pleiotropic Essence andEmerging Paradigms in Bioavailability Modulation. CTMC. 2023, 23(15), 1395–1413. DOI: 10.2174/1568026623666230103163023.
  • Bhat, S. S.; Prasad, S. K.; Shivamallu, C.; Prasad, K. S.; Syed, A.; Reddy, P.; Cull, C. A.; Amachawadi, R. G. Genistein: A Potent Anti-Breast Cancer Agent. Curr. Issues Mol. Biol. 2021, 43(3), 1502–1517. DOI: 10.3390/cimb43030106.
  • Kim, G. Y.; Suh, J.; Jang, J. H.; Kim, D. H.; Park, O. J.; Park, S. K.; Surh, Y. J. Genistein Inhibits Proliferation of BRCA1 Mutated Breast Cancer Cells: The GPR30-Akt Axis as a Potential Target. J. Cancer Prev. 2019, 24(4), 197–207. DOI: 10.15430/JCP.2019.24.4.197.
  • Ma, X.; Yu, X.; Min, J.; Chen, X.; Liu, R.; Cui, X.; Cheng, J.; Xie, M.; Diel, P.; Hu, X. Genistein Interferes with Antitumor Effects of Cisplatin in an Ovariectomized Breast Cancer Xenograft Tumor Model. Toxicol. Lett. 2022, 355, 106–115. DOI: 10.1016/j.toxlet.2021.11.013.
  • Mukund, V.; Saddala, M. S.; Farran, B.; Mannavarapu, M.; Alam, A.; Nagaraju, G. P. Molecular Docking Studies of Angiogenesis Target Protein HIF-1α and Genistein in Breast Cancer. Gene. 2019, 701, 169–172. DOI: 10.1016/j.gene.2019.03.062.
  • Kaushik, S.; Shyam, H.; Agarwal, S.; Sharma, R.; Nag, T. C.; Dwivedi, A. K.; Balapure, A. K. Genistein Potentiates Centchroman Induced Antineoplasticity in Breast Cancer via PI3K/Akt Deactivation and ROS Dependent Induction of Apoptosis. Life. sci. 2019, 239, 117073. DOI: 10.1016/j.lfs.2019.117073.
  • Jiang, H.; Fan, J.; Cheng, L.; Hu, P.; Liu, R. The anticancer activity of genistein is increased in estrogen receptor beta 1-positive breast cancer cells. Onco. Targets Ther. 2018, 11, 8153–8163. DOI: 10.2147/OTT.S182239.
  • Li, T.; Kuang, T.; Yang, Z.; Zhang, Q.; Zhang, W.; Fan, Y. Co-Treatment with Everolimus, an MTOR-Specific Antagonist, or Downregulation of ELK1 Enhances the Sensitivity of Pancreatic Cancer Cells to Genistein. Front Cell Dev Biol. 2021, 9, 633035. DOI: 10.3389/fcell.2021.633035.
  • Mesmar, F.; Dai, B.; Ibrahim, A.; Hases, L.; Jafferali, M. H.; Jose Augustine, J.; DiLorenzo, S.; Kang, Y.; Zhao, Y.; Wang, J.; et al. Clinical Candidate and Genistein Analogue AXP107-11 Has Chemoenhancing Functions in Pancreatic Adenocarcinoma Through G Protein-Coupled Estrogen Receptor Signaling. Cancer Med. 2019, 8(18), 7705–7719.
  • Ma, C. H.; Zhang, Y. X.; Tang, L. H.; Yang, X. J.; Cui, W. M.; Han, C. C.; Ji, W. Y. MicroRNA-1469, a p53-Responsive microRna Promotes Genistein Induced Apoptosis by Targeting Mcl1 in Human Laryngeal Cancer Cells. Biomed. Pharmacother. 2018, 106, 665–671. DOI: 10.1016/j.biopha.2018.07.005.
  • Xia, J.; Cheng, L.; Mei, C.; Ma, J.; Shi, Y.; Zeng, F.; Wang, Z.; Wang, Z. Genistein Inhibits Cell Growth and Invasion Through Regulation of MiR-27a in Pancreatic Cancer Cells. Curr. Pharm. Des. 2014, 20(33), 5348–5353. DOI: 10.2174/1381612820666140128215756.
  • Ma, J.; Zeng, F.; Ma, C.; Pang, H.; Fang, B.; Lian, C.; Yin, B.; Zhang, X.; Wang, Z.; Xia, J. Synergistic Reversal Effect of Epithelial-To-Mesenchymal Transition by MiR-223 Inhibitor and Genistein in Gemcitabine-Resistant Pancreatic Cancer Cells. Am. J. Cancer Res. 2016, 6(6), 1384–1395.
  • Ma, J.; Cheng, L.; Liu, H.; Zhang, J.; Shi, Y.; Zeng, F.; Miele, L.; Sarkar, F. H.; Xia, J.; Wang, Z. Genistein down-regulates miR-223 expression in pancreatic cancer cells. Curr. Drug Targets. 2013, 14(10), 1150–1156. DOI: 10.2174/13894501113149990187.
  • Ji, X.; Liu, K.; Li, Q.; Shen, Q.; Han, F.; Ye, Q.; Zheng, C. A Mini-Review of Flavone Isomers Apigenin and Genistein in Prostate Cancer Treatment. Front Pharmacol. 2022, 13, 851589. DOI: 10.3389/fphar.2022.851589.
  • Shafiee, G.; Saidijam, M.; Tayebinia, H.; Khodadadi, I. Beneficial Effects of Genistein in Suppression of Proliferation, Inhibition of Metastasis, and Induction of Apoptosis in PC3 Prostate Cancer Cells. Arch. Physiol. Biochem. 2022, 128(3), 694–702. DOI: 10.1080/13813455.2020.1717541.
  • Khamesi, S. M.; Salehi Barough, M.; Zargan, J.; Shayesteh, M.; Banaee, N.; Haji Noormohammadi, A.; Keshavarz Alikhani, H.; Mousavi, M. Evaluation of Anticancer and Cytotoxic Effects of Genistein on PC3 Prostate Cell Line Under Three-Dimensional Culture Medium. Iran. Biomed. J. 2022, 26(5), 380–388. DOI: 10.52547/ibj.3711.
  • Yu, X.; Yan, J.; Li, Y.; Cheng, J.; Zheng, L.; Fu, T.; Zhu, Y. Inhibition of Castration-Resistant Prostate Cancer Growth by Genistein Through Suppression of AKR1C3. Food & Nutrition Research. 2023, 67. DOI: 10.29219/fnr.v67.9024.
  • Tang, Q.; Ma, J.; Sun, J.; Yang, L.; Yang, F.; Zhang, W.; Li, R.; Wang, L.; Wang, Y.; Wang, H. Genistein and AG1024 Synergistically Increase the Radiosensitivity of Prostate Cancer Cells. Oncol. Rep. 2018, 40(2), 579–588. DOI: 10.3892/or.2018.6468.
  • Batra, N.; Sam, A.; Woldemariam, T.; Talbott, G.; de Vere White, R. W.; Ghosh, P. M.; Gaikwad, N. W.; Kotchoni, S. O.; Vinall, R. L. Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells. Biomedicines. 2020, 8(8), 282. DOI: 10.3390/biomedicines8080282.
  • Tian, T.; Li, J.; Li, B.; Wang, Y.; Li, M.; Ma, D.; Wang, X. Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells. Tumour Biol. 2014, 35(5), 4137–4145. DOI: 10.1007/s13277-013-1542-0.
  • Song, Y. Y.; Yuan, Y.; Shi, X.; Che, Y. Y. Improved Drug Delivery and Anti-Tumor Efficacy of Combinatorial Liposomal Formulation of Genistein and Plumbagin by Targeting Glut1 and Akt3 Proteins in Mice Bearing Prostate Tumor. Colloids Surf. B Biointerfaces. 2020, 190, 110966. DOI: 10.1016/j.colsurfb.2020.110966.
  • Lee, S. R.; Kwon, S. W.; Lee, Y. H.; Kaya, P.; Kim, J. M.; Ahn, C.; Jung, E. M.; Lee, G. S.; An, B. S.; Jeung, E. B.; et al. Dietary Intake of Genistein Suppresses Hepatocellular Carcinoma Through AMPK-Mediated Apoptosis and Anti-Inflammation. BMC Cancer. 2019, 19(1), 6. DOI: 10.1186/s12885-018-5222-8.
  • Yang, X.; Jiang, W.; Kong, X.; Zhou, X.; Zhu, D.; Kong, L. Genistein Restricts the Epithelial Mesenchymal Transformation (EMT) and Stemness of Hepatocellular Carcinoma via Upregulating MiR-1275 to Inhibit the EIF5A2/PI3K/Akt Pathway. Biol. 2022, 11(10), 1383. DOI: 10.3390/biology11101383.
  • Sanaei, M.; Kavoosi, F.; Roustazadeh, A.; Golestan, F. Effect of Genistein in Comparison with Trichostatin a on Reactivation of DNMTs Genes in Hepatocellular Carcinoma. J. Clin. Transl. Hepatol. 2018, 6(2), 141–146. DOI: 10.14218/JCTH.2018.00002.
  • Dai, W.; Wang, F.; He, L.; Lin, C.; Wu, S.; Chen, P.; Zhang, Y.; Shen, M.; Wu, D.; Wang, C., et al. Genistein Inhibits Hepatocellular Carcinoma Cell Migration by Reversing the Epithelial-Mesenchymal Transition: Partial Mediation by the Transcription Factor NFAT1. Mol. Carcinog. 2015, 54(4), 301–311. DOI: 10.1002/mc.22100.
  • Lepri, S. R.; Sartori, D.; Semprebon, S. C.; Baranoski, A.; Coatti, G. C.; Mantovani, M. S. Genistein Affects Expression of Cytochrome P450 (CYP450) Genes in Hepatocellular Carcinoma (HEPG2/C3A) Cell Line. Drug Metab. Lett. 2018, 12(2), 138–144. DOI: 10.2174/1872312812666180709150440.
  • Sanaei, M.; Kavoosi, F.; Valiani, A.; Ghobadifar, M. A. Effect of Genistein on Apoptosis and Proliferation of Hepatocellular Carcinoma Hepa1-6 Cell Line. Int. J. Prev. Med. 2018, 9(1), 12. DOI: 10.4103/ijpvm.IJPVM_249_16.
  • Dastjerdi, M. N.; Kavoosi, F.; Valiani, A.; Esfandiari, E.; Sanaei, M.; Sobhanian, S.; Hakemi, M. G.; Mobarakian, M. Inhibitory Effect of Genistein on PLC/PRF5 Hepatocellular Carcinoma Cell Line. Int. J. Prev. Med. 2015, 6(1), 54. DOI: 10.4103/2008-7802.158914.
  • Roh, T.; Kim, S. W.; Moon, S. H.; Nam, M. J. Genistein induces apoptosis by down-regulating thioredoxin-1 in human hepatocellular carcinoma SNU-449 cells. Food. Chem. Toxicol. 2016, 97, 127–134. DOI: 10.1016/j.fct.2016.09.003.
  • Yu, D.; Shin, H. S.; Lee, Y. S.; Lee, D.; Kim, S.; Lee, Y. C. Genistein Attenuates Cancer Stem Cell Characteristics in Gastric Cancer Through the Downregulation of Gli1. Oncol. Rep. 2014, 31(2), 673–678. DOI: 10.3892/or.2013.2893.
  • Huang, W.; Wan, C.; Luo, Q.; Huang, Z.; Luo, Q. Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer. Int. J. Mol. Sci. 2014, 15(3), 3432–3443. DOI: 10.3390/ijms15033432.
  • Hou, S. G. Genistein: Therapeutic and Preventive Effects, Mechanisms, and Clinical Application in Digestive Tract Tumor. Evid. Based Complement. Alternat. Med. 2022, 2022, 1–10. DOI: 10.1155/2022/5957378.
  • Moreno-Quintero, G.; Castrillón-Lopez, W.; Herrera-Ramirez, A.; Yepes-Pérez, A. F.; Quintero-Saumeth, J.; Cardona-Galeano, W. Synthesis and Chemopreventive Potential of 5-Fu/genistein Hybrids on Colorectal Cancer Cells. Pharm. 2022, 15(10), 1299. DOI: 10.3390/ph15101299.
  • Alorda-Clara, M.; Torrens-Mas, M.; Morla-Barcelo, P. M.; Roca, P.; Sastre-Serra, J.; Pons, D. G.; Oliver, J. High Concentrations of Genistein Decrease Cell Viability Depending on Oxidative Stress and Inflammation in Colon Cancer Cell Lines. Int. J. Mol. Sci. 2022, 23(14), 7526. DOI: 10.3390/ijms23147526.
  • Castaño, M.; Martínez, E.; Osorio, M.; Castro, C. Development of Genistein Drug Delivery Systems Based on Bacterial Nanocellulose for Potential Colorectal Cancer Chemoprevention: Effect of Nanocellulose Surface Modification on Genistein Adsorption. Molecules. 2022, 27(21), 7201. DOI: 10.3390/molecules27217201.
  • Liang, Y. S.; Qi, W. T.; Guo, W.; Wang, C. L.; Hu, Z. B.; Li, A. K. Genistein and Daidzein Induce Apoptosis of Colon Cancer Cells by Inhibiting the Accumulation of Lipid Droplets. Food Nutr. Res. 2018, 62. DOI: 10.29219/fnr.v62.1384.
  • Pool, H.; Campos-Vega, R.; Herrera-Hernández, M. G.; García-Solis, P.; García-Gasca, T.; Sánchez, I. C.; Luna-Bárcenas, G.; Vergara-Castañeda, H. Development of Genistein-PEGylated Silica Hybrid Nanomaterials with Enhanced Antioxidant and Antiproliferative Properties on HT29 Human Colon Cancer Cells. Am. J. Transl. Res. 2018, 10(8), 2306–2323.
  • Zhou, P.; Wang, C.; Hu, Z.; Chen, W.; Qi, W.; Li, A. Genistein Induces Apoptosis of Colon Cancer Cells by Reversal of Epithelial-To-Mesenchymal via a Notch1/nf-Κb/slug/e-Cadherin Pathway. BMC Cancer. 2017, 17(1), 813. DOI: 10.1186/s12885-017-3829-9.
  • Shafiee, G.; Saidijam, M.; Tavilani, H.; Ghasemkhani, N.; Khodadadi, I. Genistein Induces Apoptosis and Inhibits Proliferation of HT29 Colon Cancer Cells. Int. J. Mol. Cell Med. 2016, 5(3), 178–191.
  • Zhang, Z.; Wang, C. Z.; Du, G. J.; Qi, L. W.; Calway, T.; He, T. C.; Du, W.; Yuan, C. S. Genistein Induces G2/M Cell Cycle Arrest and Apoptosis via ATM/p53-Dependent Pathway in Human Colon Cancer Cells. Int. J. Oncol. 2013, 43(1), 289–296. DOI: 10.3892/ijo.2013.1946.
  • Han, J.; Kurita, Y.; Isoda, H. Genistein-Induced G2/M Cell Cycle Arrest of Human Intestinal Colon Cancer Caco-2 Cells is Associated with Cyclin B1 and Chk2 Down-Regulation. Cytotechnology. 2013, 65(6), 973–978. DOI: 10.1007/s10616-013-9592-0.
  • Lepri, S. R.; Zanelatto, L. C.; da Silva, P. B.; Sartori, D.; Ribeiro, L. R.; Mantovani, M. S. Effects of Genistein and Daidzein on Cell Proliferation Kinetics in HT29 Colon Cancer Cells: The Expression of CTNNBIP1 (β-Catenin), APC (Adenomatous Polyposis Coli) and BIRC5 (Survivin). Hum. Cell. 2014, 27(2), 78–84. DOI: 10.1007/s13577-012-0051-6.
  • Qin, J.; Chen, J. X.; Zhu, Z.; Teng, J. A. Genistein Inhibits Human Colorectal Cancer Growth and Suppresses MiR-95, Akt and SGK1. Cell. Physiol. Biochem. 2015, 35(5), 2069–2077. DOI: 10.1159/000374013.
  • Hussein, A. M.; Attaai, A. H.; Zahran, A. M. Genistein anticancer efficacy during induced oral squamous cell carcinoma: an experimental study. J. Egypt. Natl. Canc. Inst. 2022, 34(1), 37. DOI: 10.1186/s43046-022-00140-5.
  • Dev, A.; Sardoiwala, M. N.; Kushwaha, A. C.; Karmakar, S.; Choudhury, S. R. Genistein Nanoformulation Promotes Selective Apoptosis in Oral Squamous Cell Carcinoma Through Repression of 3PK-EZH2 Signalling Pathway. Phytomedicine. 2021, 80, 153386. DOI: 10.1016/j.phymed.2020.153386.
  • Bae, M. G.; Hwang-Bo, J.; Lee, D. Y.; Lee, Y. H.; Chung, I. S. Effects of 6,8-Diprenylgenistein on VEGF-A-Induced Lymphangiogenesis and Lymph Node Metastasis in an Oral Cancer Sentinel Lymph Node Animal Model. Int. J. Mol. Sci. 2021, 22(2), 770. DOI: 10.3390/ijms22020770.
  • Hsieh, P. L.; Liao, Y. W.; Hsieh, C. W.; Chen, P. N.; Yu, C. C. Soy Isoflavone Genistein Impedes Cancer Stemness and Mesenchymal Transition in Head and Neck Cancer Through Activating MiR-34a/RTCB Axis. Nutrients. 2020, 12(7), 1924. DOI: 10.3390/nu12071924.
  • Ardito, F.; Di Gioia, G.; Pellegrino, M. R.; Muzio, L. L. Genistein as a Potential Anticancer Agent Against Head and Neck Squamous Cell Carcinoma. Curr. Top. Med. Chem. 2018, 18(3), 174–181. DOI: 10.2174/1568026618666180116122650.
  • Zhang, C.; Lv, B.; Yi, C.; Cui, X.; Sui, S.; Li, X.; Qi, M.; Hao, C.; Han, B.; Liu, Z. Genistein Inhibits Human Papillary Thyroid Cancer Cell Detachment, Invasion and Metastasis. J. Cancer. 2019, 10(3), 737–748. DOI: 10.7150/jca.28111.
  • Schroeter, A.; Aichinger, G.; Stornig, K.; Marko, D. Impact of Oxidative Metabolism on the Cytotoxic and Genotoxic Potential of Genistein in Human Colon Cancer Cells. Mol. Nutr. Food Res. 2019, 63(2), e1800635. DOI: 10.1002/mnfr.201800635.
  • Xi, P.; Zhang, S. The Research of Apoptosis and Proliferation Inhibition of Human Laryngeal Carcinoma Cell Line Hep-2 Induced by Genistein. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015, 29(7), 638–641.
  • Chen, X.; Wu, Y.; Gu, J.; Liang, P.; Shen, M.; Xi, J.; Qin, J. Anti-invasive effect and pharmacological mechanism of genistein against colorectal cancer. BioFactors. 2020, 46(4), 620–628. DOI: 10.1002/biof.1627.
  • Sundaram, M. K.; Ansari, M. Z.; Al Mutery, A.; Ashraf, M.; Nasab, R.; Rai, S.; Rais, N.; Hussain, A. Genistein Induces Alterations of Epigenetic Modulatory Signatures in Human Cervical Cancer Cells. Anti Cancer Agents Med. Chem. 2018, 18(3), 412–421. DOI: 10.2174/1871520617666170918142114.
  • Liu, X.; Li, P.; Hirayama, R.; Niu, Y.; Liu, X.; Chen, W.; Jin, X.; Zhang, P.; Ye, F.; Zhao, T., et al. Genistein Sensitizes Glioblastoma Cells to Carbon Ions via Inhibiting DNA-PKcs Phosphorylation and Subsequently Repressing NHEJ and Delaying HR Repair Pathways. Radiother. Oncol. 2018, 129(1), 84–94. DOI: 10.1016/j.radonc.2018.04.005.
  • Yoriki, K.; Mori, T.; Aoyama, K.; Tarumi, Y.; Kataoka, H.; Kokabu, T.; Kitawaki, J. Genistein Induces Long-Term Expression of Progesterone Receptor Regardless of Estrogen Receptor Status and Improves the Prognosis of Endometrial Cancer Patients. Sci. Rep. 2022, 12(1), 10303. DOI: 10.1038/s41598-022-13842-6.
  • Carbonel, A. A.; Calió, M. L.; Santos, M. A.; Bertoncini, C. R.; Sasso Gda, S.; Simões, R. S.; Simões, M. J.; JM, S., Jr. Soybean Isoflavones Attenuate the Expression of Genes Related to Endometrial Cancer Risk. Climacteric. 2015, 18(3), 389–398. DOI: 10.3109/13697137.2014.964671.
  • Buathong, N.; Poonyachoti, S.; Deachapunya, C. Isoflavone Genistein Modulates the Protein Expression of Toll-like Receptors in Cancerous Human Endometrial Cells. J. Med. Assoc. Thai. 2015, 98(Suppl 9), S31–8.
  • Chen, Y.; Bai, J.; Xu, J.; Song, X. Effects of 7-Difluoromethy-5, 4’-Dimethoxygenistein on Proliferation and Apoptosis of Human Cervical Cancer Cells and Its Mechanism. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016, 41(5), 463–470. DOI: 10.11817/j.issn.1672-7347.2016.05.003.
  • Naciff, J. M.; Khambatta, Z. S.; Carr, G. J.; Tiesman, J. P.; Singleton, D. W.; Khan, S. A.; Daston, G. P. Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein. Toxicol. Sci. 2016, 151(1), 71–87. DOI: 10.1093/toxsci/kfw024.
  • Xu, H.; Ma, H.; Zha, L.; Li, Q.; Pan, H.; Zhang, L. Genistein Promotes Apoptosis of Lung Cancer Cells Through the IMPDH2/AKT1 Pathway. Am. J. Transl. Res. 2022, 14(10), 7040–7051.
  • Fu, Z.; Cao, X.; Liu, L.; Cao, X.; Cui, Y.; Li, X.; Quan, M.; Ren, K.; Chen, A.; Xu, C., et al. Genistein Inhibits Lung Cancer Cell Stem-Like Characteristics by Modulating MnSod and FoxM1 Expression. Oncol. Lett. 2020, 20(3), 2506–2515. DOI: 10.3892/ol.2020.11802.
  • Yu, Y.; Xing, Y.; Zhang, Q.; Zhang, Q.; Huang, S.; Li, X.; Gao, C. Soy isoflavone genistein inhibits hsa_circ_0031250/miR-873-5p/FOXM1 axis to suppress non-small-cell lung cancer progression. IUBMB Life. 2021, 73(1), 92–107. DOI: 10.1002/iub.2404.
  • Yang, Y.; Zang, A.; Jia, Y.; Shang, Y.; Zhang, Z.; Ge, K.; Zhang, J.; Fan, W.; Wang, B. Genistein Inhibits A549 Human Lung Cancer Cell Proliferation via MiR-27a and MET Signaling. Oncol. Lett. 2016, 12(3), 2189–2193. DOI: 10.3892/ol.2016.4817.
  • Wu, T. C.; Lin, Y. C.; Chen, H. L.; Huang, P. R.; Liu, S. Y.; Yeh, S. L. The Enhancing Effect of Genistein on Apoptosis Induced by Trichostatin a in Lung Cancer Cells with Wild Type p53 Genes is Associated with Upregulation of Histone Acetyltransferase. Toxicol. Appl. Pharmacol. 2016, 292, 94–102. DOI: 10.1016/j.taap.2015.12.028.
  • Kamel, N. M.; Helmy, M. W.; Abdelfattah, E. Z.; Khattab, S. N.; Ragab, D.; Samaha, M. W.; Fang, J. Y.; Elzoghby, A. O. Inhalable Dual-Targeted Hybrid Lipid Nanocore-Protein Shell Composites for Combined Delivery of Genistein and All-Trans Retinoic Acid to Lung Cancer Cells. ACS Biomater. Sci. Eng. 2020, 6(1), 71–87. DOI: 10.1021/acsbiomaterials.8b01374.
  • Zhang, C.; Yang, F.; Ni, S.; Teng, W.; Ning, Y. Drug-Target-Disease Network Analysis of Gene-Phenotype Connectivity for Genistein in Ovarian Cancer. Onco. Targets Ther. 2018, 11, 8901–8908. DOI: 10.2147/OTT.S183302.
  • Liu, D.; Yan, L.; Wang, L.; Tai, W.; Wang, W.; Yang, C. Genistein Enhances the Effect of Cisplatin on the Inhibition of Non-Small Cell Lung Cancer A549 Cell Growth in vitro and in vivo. Oncol. Lett. 2014, 8(6), 2806–2810. DOI: 10.3892/ol.2014.2597.
  • Yazdani, Y.; Sharifi Rad, M. R.; Taghipour, M.; Chenari, N.; Ghaderi, A.; Razmkhah, M. Genistein Suppression of Matrix Metalloproteinase 2 (MMP-2) and Vascular Endothelial Growth Factor (VEGF) Expression in Mesenchymal Stem Cell Like Cells Isolated from High and Low Grade Gliomas. Asian Pac. J. Cancer Prev. 2016, 17(12), 5303–5307. DOI: 10.22034/APJCP.2016.17.12.5303.
  • Shahmoradi, M.; Banisharif-Dehkordi, F.; Kouhihabibidehkordi, M.; GhatrehSamani, M.; Jami, M. S.; Shirzad, H.; Pourgheysari, B. Molecular Effects of Genistein, as a Potential Anticancer Agent, on CXCR-4 and VEGF Pathway in Acute Lymphoblastic Leukemia. Mol. Biol. Rep. 2022, 49(6), 4161–4170. DOI: 10.1007/s11033-022-07163-0.
  • Ghasemi Goorbandi, R.; Mohammadi, M. R.; Malekzadeh, K. Synthesizing Efficacious Genistein in Conjugation with Superparamagnetic Fe3O4 Decorated with Bio-Compatible Carboxymethylated Chitosan Against Acute Leukemia Lymphoma. Biomater. Res. 2020, 24(1), 9. DOI: 10.1186/s40824-020-00187-2.
  • Abedi Nejad, M.; Nikbakht, M.; Afsa, M.; Malekzadeh, K. Restraining the Proliferation of Acute Lymphoblastic Leukemia Cells by Genistein Through Up-Regulation of B-Cell Translocation Gene-3 at Transcription Level. Galen. Med. J. 2019, 8, e1229. DOI: 10.31661/gmj.v8i0.1229.
  • Hsiao, Y. C.; Peng, S. F.; Lai, K. C.; Liao, C. L.; Huang, Y. P.; Lin, C. C.; Lin, M. L.; Liu, K. C.; Tsai, C. C.; Ma, Y. S., et al. Genistein Induces Apoptosis in vitro and Has Antitumor Activity Against Human Leukemia HL-60 Cancer Cell Xenograft Growth in vivo. Environ. Toxicol. 2019, 34(4), 443–456. DOI: 10.1002/tox.22698.
  • Hsiao, Y. C.; Chueh, F. S.; Ma, Y. S.; Lien, J. C.; Hsia, T. C.; Huang, W. W.; Chou, Y. C.; Chen, P. Y.; Chung, J. G.; Chen, H. Y., et al. Genistein Enhances the Effects of L-Asparaginase on Inducing Cell Apoptosis in Human Leukemia Cancer HL-60 Cells. Environ. Toxicol. 2021, 36(5), 764–772. DOI: 10.1002/tox.23078.
  • Narasimhan, K.; Lee, Y. M.; Lim, T. K.; Port, S. A.; Han, J. H.; Chen, C. S.; Lin, Q. Genistein Exerts Anti-Leukemic Effects on Genetically Different Acute Myeloid Leukemia Cell Lines by Inhibiting Protein Synthesis and Cell Proliferation While Inducing Apoptosis – Molecular Insights from an iTraq™ Quantitative Proteomics Study. Oncoscience. 2015, 2(2), 111–124. DOI: 10.18632/oncoscience.120.
  • Ozturk, S. A.; Alp, E.; Yar Saglam, A. S.; Konac, E.; Menevse, E. S. The Effects of Thymoquinone and Genistein Treatment on Telomerase Activity, Apoptosis, Angiogenesis, and Survival in Thyroid Cancer Cell Lines. J. Cancer Res. Ther. 2018, 14(2), 328–334. DOI: 10.4103/0973-1482.202886.
  • Ferrari, S. M.; Antonelli, A.; Guidi, P.; Bernardeschi, M.; Scarcelli, V.; Fallahi, P.; Frenzilli, G. Genotoxicity Evaluation of the Soybean Isoflavone Genistein in Human Papillary Thyroid Cancer Cells. Study of Its Potential Use in Thyroid Cancer Therapy. Nutr. Cancer. 2019, 71(8), 1335–1344. DOI: 10.1080/01635581.2019.1604004.
  • Zhao, D.; Yin, J.; Wu, S.; Wu, Z.; Pan, H. Effects of Genistein on Proliferation and Invasion of Human Thyroid Squamous Cell Carcinoma SW579 Cells. Wei Sheng Yan Jiu. 2018, 47(6), 984–992.
  • Park, C.; Cha, H. J.; Lee, H.; Hwang-Bo, H.; Ji, S. Y.; Kim, M. Y.; Hong, S. H.; Jeong, J. W.; Han, M. H.; Choi, S. H., et al. Induction of G2/M Cell Cycle Arrest and Apoptosis by Genistein in Human Bladder Cancer T24 Cells Through Inhibition of the ROS-Dependent PI3k/Akt Signal Transduction Pathway. Antioxidants (Basel). 2019, 8(9), 327. DOI: 10.3390/antiox8090327.
  • Li, E.; Zhang, T.; Sun, X.; Li, Y.; Geng, H.; Yu, D.; Zhong, C. Sonic Hedgehog Pathway Mediates Genistein Inhibition of Renal Cancer Stem Cells. Oncol. Lett. 2019, 18(3), 3081–3091. DOI: 10.3892/ol.2019.10657.
  • Hirata, H.; Ueno, K.; Nakajima, K.; Tabatabai, Z. L.; Hinoda, Y.; Ishii, N.; Dahiya, R. Genistein Downregulates Onco-MiR-1260b and Inhibits Wnt-Signalling in Renal Cancer Cells. Br. J. Cancer. 2013, 108(10), 2070–2078. DOI: 10.1038/bjc.2013.173.
  • Imai-Sumida, M.; Dasgupta, P.; Kulkarni, P.; Shiina, M.; Hashimoto, Y.; Shahryari, V.; Majid, S.; Tanaka, Y.; Dahiya, R.; Yamamura, S. Genistein Represses HOTAIR/Chromatin Remodeling Pathways to Suppress Kidney Cancer. Cell. Physiol. Biochem. 2020, 54(1), 53–70. DOI: 10.33594/000000205.
  • Ji, Z.; Huo, C.; Yang, P. Genistein Inhibited the Proliferation of Kidney Cancer Cells via CDKN2a Hypomethylation: Role of Abnormal Apoptosis. Int. Urol. nephrol. 2020, 52(6), 1049–1055. DOI: 10.1007/s11255-019-02372-2.
  • Guo, Y.; Zhang, A.; Ding, Y.; Wang, Y.; Yuan, W. Genistein Ameliorates Parathyroid Hormone-Induced Epithelial-To-Mesenchymal Transition and Inhibits Expression of Connective Tissue Growth Factor in Human Renal Proximal Tubular Cells. Arch. Med. Sci. 2013, 9(4), 724–730. DOI: 10.5114/aoms.2013.36929.
  • Wei, D.; Yang, L.; Lv, B.; Chen, L. Genistein Suppresses Retinoblastoma Cell Viability and Growth and Induces Apoptosis by Upregulating MiR-145 and Inhibiting Its Target ABCE1. Mol. Vis. 2017, 23, 385–394.
  • Song, M.; Tian, X.; Lu, M.; Zhang, X.; Ma, K.; Lv, Z.; Wang, Z.; Hu, Y.; Xun, C.; Zhang, Z.; et al. Genistein Exerts Growth Inhibition on Human Osteosarcoma MG-63 Cells via PPARγ Pathway. Int. J. Oncol. 2015, 46(3), 1131–1140. DOI: 10.3892/ijo.2015.2829.
  • Engel, N.; Adamus, A.; Schauer, N.; Kühn, J.; Nebe, B.; Seitz, G.; Kraft, K.; Nikitovic-Tzanakaki, D. Synergistic Action of Genistein and Calcitriol in Immature Osteosarcoma MG-63 Cells by SGPL1 Up-Regulation. PLoS. One. 2017, 12(1), e0169742. DOI: 10.1371/journal.pone.0169742.
  • Sharma, M.; Arora, I.; Chen, M.; Wu, H.; Crowley, M. R.; Tollefsbol, T. O.; Li, Y. Therapeutic Effects of Dietary Soybean Genistein on Triple-Negative Breast Cancer via Regulation of Epigenetic Mechanisms. Nutrients. 2021, 13(11), 3944. DOI: 10.3390/nu13113944.
  • Sahin, K.; Yenice, E.; Bilir, B.; Orhan, C.; Tuzcu, M.; Sahin, N.; Ozercan, I. H.; Kabil, N.; Ozpolat, B.; Kucuk, O. Genistein Prevents Development of Spontaneous Ovarian Cancer and Inhibits Tumor Growth in Hen Model. Cancer Prev. Res. (Phila). 2019, 12(3), 135–146. DOI: 10.1158/1940-6207.CAPR-17-0289.
  • Wang, Y.; Li, W.; Wang, Z.; Ren, H.; Li, Y.; Zhang, Y.; Yang, P.; Pan, S. Genistein Upregulates Cyclin D1 and CDK4 Expression and Promotes the Proliferation of Ovarian Cancer OVCAR-5 Cells. Clin. Chim. Acta. 2021, 512, 100–105. DOI: 10.1016/j.cca.2019.08.023.
  • Suraweera, T. L.; Merlin, J. J.; Dellaire, G.; Xu, Z.; Rupasinghe, H. V. Genistein and Procyanidin B2 Reduce Carcinogen-Induced Reactive Oxygen Species and DNA Damage Through the Activation of Nrf2/ARE Cell Signaling in Bronchial Epithelial Cells in vitro. Int. J. Mol. Sci. 2023, 24(4), 3676. DOI: 10.3390/ijms24043676.
  • Hwang, K. A.; Park, M. A.; Kang, N. H.; Yi, B. R.; Hyun, S. H.; Jeung, E. B.; Choi, K. C. Anticancer Effect of Genistein on BG-1 Ovarian Cancer Growth Induced by 17 β-Estradiol or Bisphenol a via the Suppression of the Crosstalk Between Estrogen Receptor α and Insulin-Like Growth Factor-1 Receptor Signaling Pathways. Toxicol. Appl. Pharmacol. 2013, 272(3), 637–646. DOI: 10.1016/j.taap.2013.07.027.
  • Huang, S. L.; Chang, T. C.; Chao, C. C. K.; Sun, N. K. Role of the TLR4-Androgen Receptor Axis and Genistein in Taxol-Resistant Ovarian Cancer Cells. Biochem Pharmacol. 2020, 177, 113965. DOI: 10.1016/j.bcp.2020.113965.
  • Zhang, L.; Ma, X.; Dong, Y. Effect of Genistein on Apoptosis of Lung Adenocarcinoma A549 Cells and Expression of Apoptosis Factors. J. Buon. 2018, 23(3), 641–646.
  • Xu, L.; Xiang, J.; Shen, J.; Zou, X.; Zhai, S.; Yin, Y.; Li, P.; Wang, X.; Sun, Q. Oncogenic MicroRNA-27a is a Target for Genistein in Ovarian Cancer Cells. Anti Cancer Agents Med. Chem. 2013, 13(7), 1126–1132. DOI: 10.2174/18715206113139990006.
  • Chan, K. K. L.; Siu, M. K. Y.; Jiang, Y. X.; Wang, J. J.; Leung, T. H. Y.; Ngan, H. Y. S. Estrogen Receptor Modulators Genistein, Daidzein and ERB-041 Inhibit Cell Migration, Invasion, Proliferation and Sphere Formation via Modulation of FAK and PI3K/AKT Signaling in Ovarian Cancer. Cancer Cell Int. 2018, 18(1), 65. DOI: 10.1186/s12935-018-0559-2.
  • Rendón, J. P.; Cañas, A. I.; Correa, E.; Bedoya-Betancur, V.; Osorio, M.; Castro, C.; Naranjo, T. W. Evaluation of the Effects of Genistein in vitro as a Chemopreventive Agent for Colorectal Cancer-Strategy to Improve Its Efficiency When Administered Orally. Molecules. 2022, 27(20), 7042. DOI: 10.3390/molecules27207042.
  • Hsiao, Y. C.; Chueh, F. S.; Ma, Y. S.; Lien, J. C.; Hsia, T. C.; Huang, W. W.; Chou, Y. C.; Chen, P. Y.; Chung, J. G.; Chen, H. Y., et al. Genistein Enhances the Effects of L‐Asparaginase on Inducing Cell Apoptosis in Human Leukemia Cancer HL‐60 Cells. Environ. Toxicol. 2021, 36(5), 764–772. DOI: 10.1002/tox.23078.
  • Kim, Y. S.; Choi, K. C.; Hwang, K. A. Genistein Suppressed Epithelial-Mesenchymal Transition and Migration Efficacies of BG-1 Ovarian Cancer Cells Activated by Estrogenic Chemicals via Estrogen Receptor Pathway and Downregulation of TGF-β Signaling Pathway. Phytomedicine. 2015, 22(11), 993–999. DOI: 10.1016/j.phymed.2015.08.003.
  • Haddad, Y. H.; Said, R. S.; Kamel, R.; Morsy, E. M. E.; El-Demerdash, E. Phytoestrogen Genistein Hinders Ovarian Oxidative Damage and Apoptotic Cell Death-Induced by Ionizing Radiation: Co-Operative Role of ER-β, TGF-β, and FOXL-2. Sci. Rep. 2020, 10(1), 13551. DOI: 10.1038/s41598-020-70309-2.
  • Ning, Y.; Xu, M.; Cao, X.; Chen, X.; Luo, X. Inactivation of AKT, ERK and NF-κB by genistein derivative, 7-difluoromethoxyl-5,4’-di-n-octylygenistein, reduces ovarian carcinoma oncogenicity. Oncol. Rep. 2017, 38(2), 949–958. DOI: 10.3892/or.2017.5709.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.