Review on Icariin as A Novel Medicaments to Confront Ovarian Cancer

  • Sima Mousavi Department of Obstetrics and Gynecology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran https://orcid.org/0000-0002-6384-0627
  • Solmaz Khastehband Department of Educational Management, Islamic Azad University-South Tehran Branch, Tehran, Iran https://orcid.org/0000-0002-9527-8886
  • Sahar Poudineh School of Medicine, Mashhad Azad University, Mashhad, Iran
  • Maryam Poudineh School of Medicine, Mashhad Azad University, Mashhad, Iran https://orcid.org/0000-0002-6956-3739
  • Alireza Sarlak School of Medicine, Hamedan University, Hamedan, Iran
  • Behnaz Barghgir School of Medicine, Shahrud University, Shahrud, Iran https://orcid.org/0000-0002-0347-9278
  • Sheida Jamalnia Department of Nursing and Midwifery, Kazeroun Branch, Islamic Azad University, Kazeroun, Iran
Keywords: Ovarian Cancer, Icariin, Phytochemical, Apoptosis, Survival

Abstract

Ovarian cancer is described as one of the most common types of cancer and the leading cause of cancer-related deaths due to the high aggressiveness of this malignancy. However, the current therapeutically strategies failed to confront ovarian cancer or are accompanied by significant adverse effects leading to the recurrence of the disease and/or affecting the quality of life of survivors. On the other hand, ovarian cancer is recognized as a heterogenous disorder that is specified by alteration in a variety of molecular and cellular markers. Thereby, researchers are keen to find a novel therapeutical strategy representing high efficacy and safety, as well as be able to modulate altered biomolecules and signaling pathways. Icariin is a phytoestrogen with desired properties that are suggested for several chronic complications, particularly different types of cancer. The aim of the present study was to reveal the ameliorative characteristics of icariin and then discuss the antitumoral activities of this phytochemical against ovarian cancer with an emphasis on the modified molecular signaling pathways.

References

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33.

https://doi.org/10.3322/caac.21708

https://doi.org/10.3322/caac.21387

https://doi.org/10.3322/caac.21590

https://doi.org/10.3322/caac.21442

https://doi.org/10.3322/caac.21551

https://doi.org/10.3322/caac.21332

https://doi.org/10.3322/caac.21654

DeSantis CE, Miller KD, Dale W, Mohile SG, Cohen HJ, Leach CR, et al. Cancer statistics for adults aged 85 years and older, 2019. CA Cancer J Clin. 2019;69(6): 452-67.

https://doi.org/10.3322/caac.21577

PMid:31390062

Cabasag CJ, Fagan PJ, Ferlay J, Vignat J, Laversanne M, Liu L, et al. Ovarian cancer today and tomorrow: A global assessment by world region and Human Development Index using GLOBOCAN 2020. Int J Cancer. 2022;151(9):1535-41.

https://doi.org/10.1002/ijc.34002

PMid:35322413

Dalmartello M, La Vecchia C, Bertuccio P, Boffetta P, Levi F, Negri E, et al. European cancer mortality predictions for the year 2022 with focus on ovarian cancer. Ann Oncol. 2022;33(3):330-9.

https://doi.org/10.1016/j.annonc.2021.12.007

PMid:35090748

Funston G, Hamilton W, Abel G, Crosbie EJ, Rous B, Walter FM. The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study. PLoS Med. 2020;17(10):e1003295.

https://doi.org/10.1371/journal.pmed.1003295

PMid:33112854 PMCid:PMC7592785

Stewart C, Ralyea C, Lockwood S. Ovarian Cancer: An Integrated Review. Semin Oncol Nurs. 2019;35(2):151-6.

https://doi.org/10.1016/j.soncn.2019.02.001

PMid:30867104

Kaku T, Ogawa S, Kawano Y, Ohishi Y, Kobayashi H, Hirakawa T, et al. Histological classification of ovarian cancer. Med Electron Microsc. 2003;36(1):9-17.

https://doi.org/10.1007/s007950300002

PMid:12658347

Iyshwarya B, Mohammed V, Veerabathiran R. Genetics of endometriosis and its association with ovarian cancer. Clin Obstet Gynecol. 2021;1(4):177-85.

https://doi.org/10.1016/j.gocm.2021.09.001

Hermens M, van Altena AM, Nieboer TE, Schoot BC, Van Vliet HA, Siebers AG, et al. Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study. Am J Obstet Gynecol. 2020;223(1):107.e1-11.

https://doi.org/10.1016/j.ajog.2020.01.041

PMid:31981507

Oronsky B, Ray CM, Spira AI, Trepel JB, Carter CA, Cottrill HM. A brief review of the management of platinum-resistant-platinum-refractory ovarian cancer. Med Oncol. 2017;34(6):1-7.

https://doi.org/10.1007/s12032-017-0960-z

PMid:28444622

Pelegrina LT, De Los Ángeles Sanhueza M, Cáceres ARR, Cuello-Carrión D, Rodríguez CE, Laconi MR. Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines. J Steroid Biochem Mol Biol. 2020;196:105492.

https://doi.org/10.1016/j.jsbmb.2019.105492

PMid:31614205

Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet. 2017;41:3-14.

https://doi.org/10.1016/j.bpobgyn.2016.08.006

PMid:27743768

Lheureux S, Braunstein M, Oza AM. Epithelial ovarian cancer: evolution of management in the era of precision medicine. CA Cancer J Clin. 2019;69(4):280-304.

https://doi.org/10.3322/caac.21559

PMid:31099893

Boussios S, Mikropoulos C, Samartzis E, Karihtala P, Moschetta M, Sheriff M, et al. Wise management of ovarian cancer: on the cutting edge. J Pers Med. 2020;10(2):41.

https://doi.org/10.3390/jpm10020041

PMid:32455595 PMCid:PMC7354604

Tang AQ, Cao XC, Tian L, He L, Liu F. Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3-derived sphere-forming cells. Mol Med Report. 2015;11(3):2221-6.

https://doi.org/10.3892/mmr.2014.2974

PMid:25405327

Abdulla KN, Majeed AT, Rasoul NS. Correlation of Premature ovarian insufficiency with chemotherapy treatment. Eurasian J Med. 2022;10:6-10.

Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol. 2020;96:316-26.

https://doi.org/10.1016/j.reprotox.2020.07.015

PMid:32810592

Coffman LG, Orellana TJ, Liu T, Frisbie LG, Normolle D, Griffith K, et al. Phase I trial of ribociclib with platinum chemotherapy in recurrent ovarian cancer. JCI Insight. 2022;7(18):e160573.

https://doi.org/10.1172/jci.insight.160573

PMid:35972817 PMCid:PMC9675476

Sharma P, Georgy JT, Andrews AG, John AO, Joel A, Chacko RT, et al. Anemia requiring transfusion in breast cancer patients on dose-dense chemotherapy: Prevalence, risk factors, cost and effect on disease outcome. Support Care Cancer. 2022;30(6):5519-26.

https://doi.org/10.1007/s00520-022-06970-2

PMid:35314996 PMCid:PMC8937495

Praiss A, Moukarzel L, Chi D, Sonoda Y, Roche KL, Gardner G, et al. Postoperative morbidity after secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer: An exploratory analysis of a randomized phase II study evaluating hyperthermic intraperitoneal chemotherapy (530). Gynecol Oncol. 2022;166:S260.

https://doi.org/10.1016/S0090-8258(22)01751-6

Wanyama FM, Tauber R, Mokomba A, Nyongesa C, Blanchard V. The Burden of Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses in Ovarian Cancer Patients in Nairobi, Kenya. Infect Dis Rep. 2022;14(3):433-45.

https://doi.org/10.3390/idr14030047

PMid:35735757 PMCid:PMC9222280

Htut TW, Thein KZ, Oo TH. Meta-analysis of randomized controlled trials on primary ambulatory thromboprophylaxis in patients with ovarian cancer receiving chemotherapy. Proc (Bayl Univ Med Cent). 2022;35(3):332-6.

https://doi.org/10.1080/08998280.2022.2026187

PMid:35518830 PMCid:PMC9037452

Beesley VL, Ross TL, King MT, Campbell R, Nagle CM, Obermair A, et al. Evaluating patient-reported symptoms and late adverse effects following completion of first-line chemotherapy for ovarian cancer using the MOST (Measure of Ovarian Symptoms and Treatment concerns). Gynecol Oncol. 2022;164(2):437-45.

https://doi.org/10.1016/j.ygyno.2021.12.006

PMid:34955238

Palagini L, Miniati M, Massa L, Folesani F, Marazziti D, Grassi L, et al. Insomnia and circadian sleep disorders in ovarian cancer: evaluation and management of underestimated modifiable factors potentially contributing to morbidity. J Sleep Res. 2022;31(3):e13510.

https://doi.org/10.1111/jsr.13510

Wu H-J, Chuang C-M, Chien C-H, Wang T-J, Liang S-Y. Changes in Depression and Sleep Quality and Associated Factors in Women Receiving Chemotherapy for Ovarian Cancer: An Observational Study. Cancer Nurs. 2022;45(4):271-9.

https://doi.org/10.1097/NCC.0000000000000986

PMid:34310385

Liu J, Nicum S, Reichardt P, Croitoru K, Illek B, Schmidinger M, et al. Assessment and management of diarrhea following VEGF receptor TKI treatment in patients with ovarian cancer. Gynecol Oncol. 2018;150(1):173-9.

https://doi.org/10.1016/j.ygyno.2018.03.058

PMid:29627080

Lv X, Chen W, Qi T, Ding Y. Advances in Cytoreductive Surgery and Combination Therapy for Ovarian Cancer. Clin. Exp. Obstet. Gynecol. 2022;49(7):166.

https://doi.org/10.31083/j.ceog4907166

Abbasi A, Movahedpour A, Amiri A, Najaf MS, Mostafavi-Pour Z. Darolutamide as a second-generation androgen receptor inhibitor in the treatment of prostate cancer. Curr Mol Med. 2021;21(4):332-46.

https://doi.org/10.2174/18755666MTA5dNjU2w

https://doi.org/10.2174/1566524020666200903120344

PMid:32881669

Samare-Najaf M, Samareh A, Jamali N, Abbasi A, Clark CC, Khorchani MJ, et al. Adverse Effects and Safety of Etirinotecan Pegol, a Novel Topoisomerase Inhibitor, in Cancer Treatment: A Systematic Review. Curr Cancer Ther Rev. 2021;17(3):234-43.

https://doi.org/10.2174/1573394717666210202103502

Hurley RM, Hendrickson AEW, Visscher DW, Ansell P, Harrell MI, Wagner JM, et al. 53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer. Gynecol Oncol. 2019;153(1):127-34.

https://doi.org/10.1016/j.ygyno.2019.01.015

PMid:30686551 PMCid:PMC6430710

Keung MYT, Wu Y, Vadgama JV. PARP inhibitors as a therapeutic agent for homologous recombination deficiency in breast cancers. J Clin Med. 2019;8(4):435.

https://doi.org/10.3390/jcm8040435

PMid:30934991 PMCid:PMC6517993

Carducci M, Shaheen M, Markman B, Hurvitz S, Mahadevan D, Kotasek D, et al. A phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors. Invest New Drugs. 2018;36(6):1060-71.

https://doi.org/10.1007/s10637-018-0625-6

PMid:29980894 PMCid:PMC6639057

Pérez-Fidalgo JA, Gambardella V, Pineda B, Burgues O, Piñero O, Cervantes A. Aurora kinases in ovarian cancer. ESMO Open. 2020;5(5):e000718.

https://doi.org/10.1136/esmoopen-2020-000718

PMid:33087400 PMCid:PMC7580081

Caumanns JJ, Wisman GBA, Berns K, Van Der Zee AG, De Jong S. ARID1A mutant ovarian clear cell carcinoma: A clear target for synthetic lethal strategies. Biochim Biophys. 2018;1870(2):176-84.

https://doi.org/10.1016/j.bbcan.2018.07.005

PMid:30025943

Ediriweera MK, Tennekoon KH, Samarakoon SR. Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance. Semin Cancer Biol. 2019;59:147-60.

https://doi.org/10.1016/j.semcancer.2019.05.012

PMid:31128298

Lengyel CG, Altuna SC, Habeeb BS, Trapani D, Khan SZ. The potential of PI3K/AKT/mTOR signaling as a druggable target for endometrial and ovarian carcinomas. Curr Drug Targets. 2020;21(10):946-61.

https://doi.org/10.2174/1389450120666191120123612

PMid:31752654

Mullen J, Kato S, Sicklick JK, Kurzrock R. Targeting ARID1A mutations in cancer. Cancer Treat Rev. 2021;100:102287.

https://doi.org/10.1016/j.ctrv.2021.102287

PMid:34619527

Mohapatra P, Singh P, Singh D, Sahoo S, Sahoo SK. Phytochemical based nanomedicine: a panacea for cancer treatment, present status and future prospective. OpenNano. 2022:100055.

https://doi.org/10.1016/j.onano.2022.100055

Samare-Najaf M, Zal F, Jamali N, Vakili S, Khodabandeh Z. Do Quercetin And Vitamin E Properties Preclude Doxorubicin-Induced Stress and Inflammation In Reproductive Tissues? Curr Cancer Ther Rev. 2022;18:292-302.

https://doi.org/10.2174/1573394718666220726105843

Sharaf MH, Abdelaziz AM, Kalaba MH, Radwan AA, Hashem AH. Antimicrobial, antioxidant, cytotoxic activities and phytochemical analysis of fungal endophytes isolated from ocimum basilicum. Appl. Biochem Biotechnol. 2022;194(3):1271-89.

https://doi.org/10.1007/s12010-021-03702-w

PMid:34661866

Jafari Khorchani M, Samare-Najaf M, Abbasi A, Vakili S, Zal F. Effects of quercetin, vitamin E, and estrogen on Metabolic-Related factors in uterus and serum of ovariectomized rat models. Gynecol Endocrinol. 2021;37(8):764-8.

https://doi.org/10.1080/09513590.2021.1879784

PMid:33525940

Jamali N, Jalali M, Saffari-Chaleshtori J, Samare-Najaf M, Samareh A. Effect of cinnamon supplementation on blood pressure and anthropometric parameters in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials. Diabetes Metab Syndr. 2020;14(2):119-25.

https://doi.org/10.1016/j.dsx.2020.01.009

PMid:32032898

Poudineh M, Ghotbi T, Azizi F, Karami N, Zolfaghari Z, Gheisari F, et al. Neuropharmaceutical Properties of Naringin Against Alzheimer's and Parkinson's Diseases. GMJ. 2022;11:e2337.

https://doi.org/10.31661/gmj.v11i.2337

Komici K, Conti V, Davinelli S, Bencivenga L, Rengo G, Filippelli A, et al. Cardioprotective effects of dietary phytochemicals on oxidative stress in heart failure by a sex-gender-oriented point of view. Oxid Med Cell Longev. 2020;2020:2176728.

https://doi.org/10.1155/2020/2176728

PMid:31998434 PMCid:PMC6975222

Abadi AJ, Mirzaei S, Mahabady MK, Hashemi F, Zabolian A, Hashemi F, et al. Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects. Phytother Res. 2022;36(1):189-213.

https://doi.org/10.1002/ptr.7305

PMid:34697839

Samare-Najaf M, Zal F, Safari S, Koohpeyma F, Jamali N. Stereological and histopathological evaluation of doxorubicin-induced toxicity in female rats' ovary and uterus and palliative effects of quercetin and vitamin E. Hum Exp Toxicol. 2020;39(12):1710-24.

https://doi.org/10.1177/0960327120937329

PMid:32666839

Pralea I-E, Petrache A-M, Tigu AB, Gulei D, Moldovan R-C, Ilieș M, et al. Phytochemicals as Regulators of Tumor Glycolysis and Hypoxia Signaling Pathways: Evidence from In Vitro Studies. Pharmaceuticals. 2022;15(7):808.

https://doi.org/10.3390/ph15070808

PMid:35890106 PMCid:PMC9315613

Dutta S, Mahalanobish S, Saha S, Ghosh S, Sil PC. Natural products: An upcoming therapeutic approach to cancer. Food Chem Toxicol. 2019;128:240-55.

https://doi.org/10.1016/j.fct.2019.04.012

PMid:30991130

Rodrigues FC, Kumar NA, Thakur G. Developments in the anticancer activity of structurally modified curcumin: An up-to-date review. Eur J Med Chem. 2019;177:76-104.

https://doi.org/10.1016/j.ejmech.2019.04.058

PMid:31129455

Abubaker M, Mohammed A, Farah A, Zhang J. Phytochemical screening by using GC-MS and FTIR spectrum analysis of fixed oil from Sudanese Ziziphus spina Christi seeds. Eurasian Chem Commun. 2021;3(4):244-56.

Errayes AO, Abdussalam-Mohammed W, Darwish MO. Review of phytochemical and medical applications of Annona muricata Fruits. JCR. 2020;2(1):70-9.

https://doi.org/10.33945/SAMI/JCR.2020.1.5

Mbabazia I, Wangila P, K'Owinoc IO. Comparison of the phytochemical composition of Euclea divinorum Hiern (Ebenaceae) leaves, tender stems and root bark. Adv J Chem B. 2020;3(3): 218-42.

Shrestha A, Pradhan R, Ghotekar S, Dahikar S, Marasini BP. Phytochemical Analysis and Anti-Microbial Activity of Desmostachya Bipinnata: A review. J Med Chem Sci. 2021;4(1):36-41.

Terwanger Philip T, Asemave K, Obochi G. Comparative Assessment of Phytochemicals in Four (4) Varieties of Ananas Comosus (L.) Merr Peels. Prog Chem Biochem Res. 2021;4(1):1-10.

Hagr T, Adam I. Phytochemical analysis, antibacterial and antioxidant activities of essential Oil from hibiscus sabdariffa (L) Seeds,(Sudanese Karkadi). Prog Chem Biochem Res. 2020;3(3):194-201.

Duru IA. Comparative Phytochemical Analysis of Brown, Green and Red Propolis from Umudike, Abia State Nigeria. Adv J Chem B. 2020;3(1):86-97.

Patra S, Pradhan B, Nayak R, Behera C, Panda KC, Das S, et al. Apoptosis and autophagy modulating dietary phytochemicals in cancer therapeutics: Current evidences and future perspectives. Phytother Res. 2021;35(8):4194-214.

https://doi.org/10.1002/ptr.7082

PMid:33749909

Chirumbolo S, Bjørklund G, Lysiuk R, Vella A, Lenchyk L, Upyr T. Targeting cancer with phytochemicals via their fine tuning of the cell survival signaling pathways. Int J Mol Sci. 2018;19(11):3568.

https://doi.org/10.3390/ijms19113568

PMid:30424557 PMCid:PMC6274856

Braicu C, Zanoaga O, Zimta A-A, Tigu AB, Kilpatrick KL, Bishayee A, et al., editors. Natural compounds modulate the crosstalk between apoptosis-and autophagy-regulated signaling pathways: Controlling the uncontrolled expansion of tumor cells. Semin Cancer Biol. 2022;80:218-36.

https://doi.org/10.1016/j.semcancer.2020.05.015

PMid:32502598

Chen CY, Kao CL, Liu CM. The cancer prevention, anti-inflammatory and anti-oxidation of bioactive phytochemicals targeting the TLR4 signaling pathway. Int J Mol Sci. 2018;19(9):2729.

https://doi.org/10.3390/ijms19092729

PMid:30213077 PMCid:PMC6164406

Ashrafizadeh M, Zarrabi A, Hashemi F, Zabolian A, Saleki H, Bagherian M, et al. Polychemotherapy with curcumin and doxorubicin via biological nanoplatforms: enhancing antitumor activity. Pharmaceutics. 2020;12(11):1084.

https://doi.org/10.3390/pharmaceutics12111084

PMid:33187385 PMCid:PMC7697177

Krajka-Kuźniak V, Baer-Dubowska W. Modulation of Nrf2 and NF-κB Signaling Pathways by Naturally Occurring Compounds in Relation to Cancer Prevention and Therapy. Are Combinations Better Than Single Compounds? Int J Mol Sci. 2021;22(15):8223.

https://doi.org/10.3390/ijms22158223

PMid:34360990 PMCid:PMC8348704

Bose S, Banerjee S, Mondal A, Chakraborty U, Pumarol J, Croley CR, et al. Targeting the JAK/STAT signaling pathway using phytocompounds for cancer prevention and therapy. Cells. 2020;9(6):1451.

https://doi.org/10.3390/cells9061451

PMid:32545187 PMCid:PMC7348822

Xu X-L, Deng S-L, Lian Z-X, Yu K. Resveratrol Targets a Variety of Oncogenic and Oncosuppressive Signaling for Ovarian Cancer Prevention and Treatment. Antioxidants. 2021;10(11):1718.

https://doi.org/10.3390/antiox10111718

PMid:34829589 PMCid:PMC8614917

Dhanaraj T, Mohan M, Arunakaran J. Quercetin attenuates metastatic ability of human metastatic ovarian cancer cells via modulating multiple signaling molecules involved in cell survival, proliferation, migration and adhesion. Arch Biochem Biophys. 2021;701:108795.

https://doi.org/10.1016/j.abb.2021.108795

PMid:33577840

Teekaraman D, Elayapillai SP, Viswanathan MP, Jagadeesan A. Quercetin inhibits human metastatic ovarian cancer cell growth and modulates components of the intrinsic apoptotic pathway in PA-1 cell line. Chem Biol Interact. 2019;300:91-100.

https://doi.org/10.1016/j.cbi.2019.01.008

PMid:30639267

Khan K, Javed Z, Sadia H, Sharifi-Rad J, Cho WC, Luparello C. Quercetin and MicroRNA interplay in apoptosis regulation in ovarian cancer. Curr Pharm Des. 2021;27(20):2328-36.

https://doi.org/10.2174/1381612826666201019102207

PMid:33076802

Yen HY, Tsao CW, Lin YW, Kuo CC, Tsao CH, Liu CY. Regulation of carcinogenesis and modulation through Wnt/β-catenin signaling by curcumin in an ovarian cancer cell line. Sci Rep. 2019;9(1):1-14.

https://doi.org/10.1038/s41598-019-53509-3

PMid:31754130 PMCid:PMC6872918

Kim MJ, Park KS, Kim KT, Gil EY. The inhibitory effect of curcumin via fascin suppression through JAK/STAT3 pathway on metastasis and recurrence of ovary cancer cells. BMC Womens Health. 2020;20(1):1-9.

https://doi.org/10.1186/s12905-020-01122-2

PMid:33213437 PMCid:PMC7678137

Mohamadian M, Bahrami A, Moradi Binabaj M, Asgharzadeh F, Ferns GA. Molecular Targets of Curcumin and Its Therapeutic Potential for Ovarian Cancer. Nutr Cancer. 2022:1-18.

https://doi.org/10.1080/01635581.2022.2049321

PMid:35266849

Ha JH, Jayaraman M, Radhakrishnan R, Gomathinayagam R, Yan M, Song YS, et al. Differential effects of thymoquinone on lysophosphatidic acid-induced oncogenic pathways in ovarian cancer cells. J Tradit Complement Med. 2020;10(3):207-16.

https://doi.org/10.1016/j.jtcme.2020.04.001

PMid:32670815 PMCid:PMC7340879

Pundir M, Sharma A, Kumar J. Phytochemicals used as inhibitors in the treatment of ovarian cancer: A Mini-review. Materials Today: Proceedings. 2022;48:1620-5.

https://doi.org/10.1016/j.matpr.2021.09.505

Qazi S, Raza K. Phytochemicals from Ayurvedic plants as potential medicaments for ovarian cancer: an in silico analysis. J Mol Model. 2021;27(4):1-14.

https://doi.org/10.1007/s00894-021-04736-x

PMid:33765217

Jin G, Palecek SP. Inductive factors for generation of pluripotent stem cell-derived cardiomyocytes. In Engineering Strategies for Regenerative Medicine. Elsevier; 2020. p. 177-242.

https://doi.org/10.1016/B978-0-12-816221-7.00006-9

PMCid:PMC7211099

Wang S, Ma J, Zeng Y, Zhou G, Wang Y, Zhou W, et al. Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review. Drug Des Devel Ther. 2021;15:3619.

https://doi.org/10.2147/DDDT.S310686

PMid:34447243 PMCid:PMC8384151

Zhang L, Wang T, Zhao B-S, Zhang J-X, Yang S, Fan C-L, et al. Effect of 2 ″-O-rhamnosyl icariside II, baohuoside I and baohuoside II in herba epimedii on cytotoxicity indices in HL-7702 and HepG2 cells. Molecules. 2019;24(7):1263.

https://doi.org/10.3390/molecules24071263

PMid:30939785 PMCid:PMC6479309

Verma A, Aggarwal K, Agrawal R, Pradhan K, Goyal A. Molecular mechanisms regulating the pharmacological actions of icariin with special focus on PI3K-AKT and Nrf-2 signaling pathways. Mol Biol Rep. 2022:1-10.

https://doi.org/10.1007/s11033-022-07778-3

PMid:35941411

Li Y, Yang Q, Yu Y. A network pharmacological approach to investigate the mechanism of action of active ingredients of epimedii herba and their potential targets in treatment of Alzheimer's disease. Med Sci Monit. 2020;26:e926295-1.

https://doi.org/10.12659/MSM.926295

Nakashima K, Miyashita H, Yoshimitsu H, Fujiwara Y, Nagai R, Ikeda T. Two new prenylflavonoids from Epimedii Herba and their inhibitory effects on advanced glycation end-products. J Nat Med. 2016;70(2):290-5.

https://doi.org/10.1007/s11418-015-0962-0

PMid:26758618

Khezri MR, Ghasemnejad-Berenji M. Icariin: A Potential Neuroprotective Agent in Alzheimer's Disease and Parkinson's Disease. Neurochem Res. 2022:1-9.

https://doi.org/10.1007/s11064-022-03667-0

PMid:35802286

Ding C. Determination of icarim in luohan jindan oral liquid by thin-layer chromatography. Chin Med J. 1990;15(10):604-6.

Zhang D, Su Y, He Q, Zhang Y, Gu N, Zhang X, et al. Icariin Exerts Estrogen-Like Actions on Proliferation of Osteoblasts in Vitro via Membrane Estrogen Receptors-Mediated Non-nuclear Effects. Iran J Pharm Res. 2022;21(1):e127000.

https://doi.org/10.5812/ijpr-127000

Wang M, Wang L, Zhou Y, Feng X, Ye C, Wang C. Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin‐1β/transforming growth factor‐β‐mediated activation of renal fibroblasts. Phytother Res. 2021;35(11):6204-15.

https://doi.org/10.1002/ptr.7256

PMid:34426999

Amanat S, Shal B, Seo EK, Ali H, Khan S. Icariin attenuates cyclophosphamide-induced cystitis via down-regulation of NF-кB and up-regulation of Nrf-2/HO-1 signaling pathways in mice model. Int Immunopharmacol. 2022;106:108604.

https://doi.org/10.1016/j.intimp.2022.108604

PMid:35149295

Sai X, Li Z, Deng G, Wang L, Xiaowu W, Nasser MI, et al. Immunomodulatory effects of icariin in a myocardial infarction mouse model. Bioengineered. 2022;13(5):12504-15.

https://doi.org/10.1080/21655979.2022.2076453

PMid:35579292 PMCid:PMC9276034

Zeng Y, Xiong Y, Yang T, Wang Y, Zeng J, Zhou S, et al. Icariin and its metabolites as potential protective phytochemicals against cardiovascular disease: from effects to molecular mechanisms. Biomed Pharmacother. 2022;147:112642.

https://doi.org/10.1016/j.biopha.2022.112642

PMid:35078094

Shaukat A, Shaukat I, Rajput SA, Shukat R, Hanif S, Huang S, et al. Icariin Alleviates Escherichia coli Lipopolysaccharide-Mediated Endometritis in Mice by Inhibiting Inflammation and Oxidative Stress. Int J Mol Sci. 2022;23(18):10219.

https://doi.org/10.3390/ijms231810219

PMid:36142129 PMCid:PMC9499631

Ji R, Wu D, Liu Q. Icariin inhibits RANKL-induced osteoclastogenesis in RAW264. 7 cells via inhibition of reactive oxygen species production by reducing the expression of NOX1 and NOX4. Biochem Biophys Res Commun. 2022;600:6-13.

https://doi.org/10.1016/j.bbrc.2022.02.023

PMid:35182975

Tang Y, Li Y, Xin D, Chen L, Xiong Z, Yu X. Icariin alleviates osteoarthritis by regulating autophagy of chondrocytes by mediating PI3K/AKT/mTOR signaling. Bioengineered. 2021;12(1):2984-99.

https://doi.org/10.1080/21655979.2021.1943602

PMid:34167449 PMCid:PMC8806900

Bi Z, Zhang W, Yan X. Anti-inflammatory and immunoregulatory effects of icariin and icaritin. Biomed Pharmacother. 2022;151:113180.

https://doi.org/10.1016/j.biopha.2022.113180

PMid:35676785

Aljehani AA, Albadr NA, Nasrullah MZ, Neamatallah T, Eid BG, Abdel-Naim AB. Icariin ameliorates metabolic syndrome-induced benign prostatic hyperplasia in rats. Environ Sci Pollut Res 2022;29(14):20370-8.

https://doi.org/10.1007/s11356-021-17245-4

PMid:34734339

Han N, Zhang B, Wei X, Yu L. The inhibitory function of icariin in cell model of benign prostatic hyperplasia by upregulation of miR‐7. Biofactors. 2019.

https://doi.org/10.1002/biof.1591

PMid:31785072

Song L, Chen X, Mi L, Liu C, Zhu S, Yang T, et al. Icariin‐induced inhibition of SIRT6/NF‐κB triggers redox mediated apoptosis and enhances anti‐tumor immunity in triple‐negative breast cancer. Cancer Sci. 2020;111(11):4242-56.

https://doi.org/10.1111/cas.14648

PMid:32926492 PMCid:PMC7648025

Cheng X, Tan S, Duan F, Yuan Q, Li Q, Deng G. Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM. Breast Cancer. 2019;26(6):766-75.

https://doi.org/10.1007/s12282-019-00980-5

PMid:31172425 PMCid:PMC6821666

Qian D, Zhu Y, Xu L, Dong T, Chen T, Yu Z. Icariin induces apoptosis in breast cancer MCF-7 cells by regulating the MELK mediated PI3K/AKT signaling pathway. Eur J Gynaecol Oncol. 2021;42(5):957-65.

https://doi.org/10.31083/j.ejgo4205144

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(3):990-6.

Li C, Yang S, Ma H, Ruan M, Fang L, Cheng J. Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways. Cancer Cell Int. 2021;21(1):1-14.

https://doi.org/10.1186/s12935-021-01910-2

Zhu F, Ren Z. Icariin inhibits the malignant progression of lung cancer by affecting the PI3K/Akt pathway through the miR-205-5p/PTEN axis. Oncol Rep. 2022;47(6):1-10.

https://doi.org/10.3892/or.2022.8326

PMid:35514319 PMCid:PMC9100476

Wu X, Kong W, Qi X, Wang S, Chen Y, Zhao Z, et al. Icariin induces apoptosis of human lung adenocarcinoma cells by activating the mitochondrial apoptotic pathway. Life Sci. 2019;239:116879.

https://doi.org/10.1016/j.lfs.2019.116879

PMid:31682849

Lei K, Ma B, Shi P, Jin C, Ling T, Li L, et al. Icariin mitigates the growth and invasion ability of human oral squamous cell carcinoma via inhibiting toll-like receptor 4 and phosphorylation of NF-κB P65. Onco Targets Ther. 2020;13:299.

https://doi.org/10.2147/OTT.S214514

PMid:32021276 PMCid:PMC6971293

Tian M, Yang S, Yan X. Icariin reduces human colon carcinoma cell growth and metastasis by enhancing p53 activities. Braz J Med Biol. 2018;51(10):e7151.

https://doi.org/10.1590/1414-431x20187151

PMid:30088538 PMCid:PMC6086551

Yin Y, Xu W, Song Y, Zhou Z, Sun X, Zhang F. Icariin Regulates the hsa_circ_0003159/eIF4A3/bcl-2 Axis to Promote Gastric Cancer Cell Apoptosis. Evid Based Complement Alternat Med. 2022;2022:1955101.

https://doi.org/10.1155/2022/1955101

PMid:35873631 PMCid:PMC9307325

Zhang F, Yin Y, Xu W, Song Y, Zhou Z, Sun X, et al. Icariin inhibits gastric cancer cell growth by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis. Hum Exp Toxicol. 2022;41:09603271221097363.

https://doi.org/10.1177/09603271221097363

PMid:35532261

Wang Y, Li Y, Zhang Y, Feng G, Yang Z, Guan Q, et al. Multi-dimensional spectrum-effect relationship of the impact of Chinese herbal formula Lichong Shengsui Yin on ovarian cancer. Molecules. 2017;22(6):979.

https://doi.org/10.3390/molecules22060979

PMid:28608834 PMCid:PMC6152777

Wang S, Gao J, Li Q, Ming W, Fu Y, Song L, et al. Study on the regulatory mechanism and experimental verification of icariin for the treatment of ovarian cancer based on network pharmacology. J Ethnopharmacol. 2020;262:113189.

https://doi.org/10.1016/j.jep.2020.113189

PMid:32736044

Gao J, Fu Y, Song L, Long M, Zhang Y, Qin J, et al. Proapoptotic Effect of Icariin on Human Ovarian Cancer Cells via the NF-κ B/PI3K-AKT Signaling Pathway: A Network Pharmacology-Directed Experimental Investigation. Am J Chin Med. 2022;50(02):589-619.

https://doi.org/10.1142/S0192415X22500239

PMid:35114909

Li J, Jiang K, Zhao F. Icariin regulates the proliferation and apoptosis of human ovarian cancer cells through microRNA-21 by targeting PTEN, RECK and Bcl-2. Oncol Rep. 2015;33(6):2829-36.

https://doi.org/10.3892/or.2015.3891

PMid:25845681

Alhakamy NA, A. Fahmy U, Badr-Eldin SM, Ahmed OA, Asfour HZ, Aldawsari HM, et al. Optimized icariin phytosomes exhibit enhanced cytotoxicity and apoptosis-inducing activities in ovarian cancer cells. Pharmaceutics. 2020;12(4):346.

https://doi.org/10.3390/pharmaceutics12040346

PMid:32290412 PMCid:PMC7238269

Fahmy UA, Fahmy O, Alhakamy NA. Optimized icariin cubosomes exhibit augmented cytotoxicity against SKOV-3 ovarian cancer cells. Pharmaceutics. 2020;13(1):20.

https://doi.org/10.3390/pharmaceutics13010020

PMid:33374293 PMCid:PMC7823966

Fu Y, Liu H, Long M, Song L, Meng Z, Lin S, et al. Icariin attenuates the tumor growth by targeting miR-1-3p/TNKS2/Wnt/β-catenin signaling axis in ovarian cancer. Front Oncol. 2022;12:940926.

https://doi.org/10.3389/fonc.2022.940926

PMid:36185280 PMCid:PMC9516086

Jiang S, Chang H, Deng S, Fan D. Icariin inhibits autophagy and promotes apoptosis in SKVCR cells through mTOR signal pathway. Cell Mol Biol. 2018;64(6):4-10.

https://doi.org/10.14715/cmb/2018.64.6.2

PMid:29808793

Jiang S, Chang H, Deng S, Fan D. 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(6):1933-42.

https://doi.org/10.3892/ijo.2019.4785

PMid:31081049 PMCid:PMC6521925

Published
2022-12-31
How to Cite
Mousavi, S., Khastehband, S., Poudineh, S., Poudineh, M., Sarlak, A., Barghgir, B., & Jamalnia, S. (2022). Review on Icariin as A Novel Medicaments to Confront Ovarian Cancer. Galen Medical Journal, 11, e2809. https://doi.org/10.31661/gmj.v11i.2809
Section
Review Article