Review On the Effects of Curcumin on Tumors of the Reproductive System
Abstract
Curcumin, a polyphenolic derivative of Curcuma longa rhizome, has numerous beneficial effects, including antibacterial, anti-inflammatory, antiviral, antioxidant, antifungal, anti-ischemic, anti-cancer, hypoglycemic, nephroprotective, antirheumatic, hepato-protective, and antimutagenic. Curcumin has indicated the capability to exert anti-cancer activity by multifunctional mechanisms, such as induction of apoptosis, inhibition of cancer cell proliferation, cell cycle regulation, chemotherapeutic intestinal absorption, and modification of several cancer cell types signaling pathways. Several studies have shown that curcumin may have protective effects against tumors of the reproductive system. Reproductive system cancers may cause many undesirable physical and, especially, mental disorders. Infertility and its mental consequences, sexual problems, chemotherapy and surgery-related adverse effects, substantial economic burden, and death are the most common complications regarding the cancers of the reproductive system. By modulating several reproductive cancer hallmarks such as signaling pathways, multiple drug resistance, cancer cell growth and proliferation, tumor angiogenesis, and transcription factors, curcumin could be used as a safe, non-toxic, cheap, and easily accessible drug for treating different types of reproductive cancers. [GMJ.2021;10:e2178]References
Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1-2):72-9.
https://doi.org/10.1016/j.jep.2005.05.011
PMid:16009521
Akram M, Shahab-Uddin AA, Usmanghani K, Hannan A, Mohiuddin E, Asif M. Curcuma longa and curcumin: a review article. Rom J Biol Plant Biol. 2010;55(2):65-70.
Mohebbati R, Anaeigoudari A, Khazdair M. The effects of Curcuma longa and curcumin on reproductive systems. Endocr Regul. 2017;51(4):220-8.
https://doi.org/10.1515/enr-2017-0024
PMid:29232190
Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxidants & redox signaling. 2008;10(3):511-46.
https://doi.org/10.1089/ars.2007.1769
PMid:18370854
Sahebkar A. Curcuminoids for the management of hypertriglyceridaemia. Nature Reviews Cardiology. 2014;11(2):123.
https://doi.org/10.1038/nrcardio.2013.140-c1
PMid:24395048
Mirzaei H, Naseri G, Rezaee R, Mohammadi M, Banikazemi Z, Mirzaei HR, et al. Curcumin: A new candidate for melanoma therapy? Int J Cancer. 2016;139(8):1683-95.
https://doi.org/10.1002/ijc.30224
PMid:27280688
Rahmani S, Asgary S, Askari G, Keshvari M, Hatamipour M, Feizi A, et al. Treatment of non‐alcoholic fatty liver disease with curcumin: A randomized placebo‐controlled trial. Phytother Res. 2016;30(9):1540-8.
https://doi.org/10.1002/ptr.5659
PMid:27270872
Esmaily H, Sahebkar A, Iranshahi M, Ganjali S, Mohammadi A, Ferns G et al. An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial. Chin J Integr Med. 2015;21(5):332-8.
https://doi.org/10.1007/s11655-015-2160-z
PMid:25776839
Sahebkar A. Molecular mechanisms for curcumin benefits against ischemic injury. Fertil Steril. 2010;94(5):e75-e6.
https://doi.org/10.1016/j.fertnstert.2010.07.1071
PMid:20797714
Ciftci O, Tanyildizi S, Godekmerdan A. Protective effect of curcumin on immune system and body weight gain on rats intoxicated with 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD). Immunopharmacol Immunotoxicol. 2010;32(1):99-104.
https://doi.org/10.3109/08923970903164318
PMid:19821784
Valsalam S, Agastian P, Esmail GA, Ghilan A-KM, Al-Dhabi NA, Arasu MV. Biosynthesis of silver and gold nanoparticles using Musa acuminata colla flower and its pharmaceutical activity against bacteria and anticancer efficacy. J Photochem Photobiol B: Biol. 2019;201:111670.
https://doi.org/10.1016/j.jphotobiol.2019.111670
PMid:31706087
Valsalam S, Agastian P, Arasu MV, Al-Dhabi NA, Ghilan A-KM, Kaviyarasu K, et al. Rapid biosynthesis and characterization of silver nanoparticles from the leaf extract of Tropaeolum majus L. and its enhanced in-vitro antibacterial, antifungal, antioxidant and anticancer properties. J Photochem Photobiol B: Biol. 2019;191:65-74.
https://doi.org/10.1016/j.jphotobiol.2018.12.010
PMid:30594044
Aggarwal BB, Surh Y-J, Shishodia S. The molecular targets and therapeutic uses of curcumin in health and disease. Springer Science & Business Media; 2007.
https://doi.org/10.1007/978-0-387-46401-5
PMid:17569205
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807-18.
https://doi.org/10.1021/mp700113r
PMid:17999464
Mirzaei H, Shakeri A, Rashidi B, Jalili A, Banikazemi Z, Sahebkar A. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother. 2017;85:102-12.
https://doi.org/10.1016/j.biopha.2016.11.098
PMid:27930973
Wahlström B, Blennow G. A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh). 1978;43(2):86-92.
https://doi.org/10.1111/j.1600-0773.1978.tb02240.x
PMid:696348
Bhavanishankar T, Shantha N, Ramesh H, Indira Murthy A, Sreenivasa Murthy V. Toxicity studies on turmeric (Curcuma longa): acute toxicity studies in rats, guineapigs and monkeys. Indian J Exp Biol. 1980;18(1):73-5.
Soni K, Kutian R. EFFECf OF ORAL CURCUMIN ADMINISTRAnON ON SERUM PEROXIDES AND CHOLESTEROL LEVELS IN HUMAN VOLUNTEERS. Indian J Physiol Phannacoll992. 1992;36(4):273-5.
Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004;10(20):6847-54.
https://doi.org/10.1158/1078-0432.CCR-04-0744
PMid:15501961
Program NT. NTP toxicology and carcinogenesis studies of turmeric oleoresin (CAS No. 8024-37-1)(major component 79%-85% curcumin, CAS No. 458-37-7) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser. 1993;427:1-275.
Farombi EO, Abarikwu SO, Adedara IA, Oyeyemi MO. Curcumin and kolaviron ameliorate di‐n‐butylphthalate‐induced testicular damage in rats. Basic Clin. Pharmacol. Toxicol.. 2007;100(1):43-8.
https://doi.org/10.1111/j.1742-7843.2007.00005.x
PMid:17214610
Cort A, Timur M, Ozdemir E, Kucuksayan E, Ozben T. Synergistic anticancer activity of curcumin and bleomycin: an in vitro study using human malignant testicular germ cells. Mol Med Report. 2012;5(6):1481-6.
https://doi.org/10.3892/mmr.2012.991
PMid:22825355
Sahoo DK, Roy A, Chainy GB. Protective effects of vitamin E and curcumin on L-thyroxine-induced rat testicular oxidative stress. Chem. Biol. Interact.. 2008;176(2-3):121-8.
https://doi.org/10.1016/j.cbi.2008.07.009
PMid:18723006
Aktas C, Kanter M, Erboga M, Ozturk S. Anti-apoptotic effects of curcumin on cadmium-induced apoptosis in rat testes. Toxicol Ind Health. 2012;28(2):122-30.
https://doi.org/10.1177/0748233711407242
PMid:21632575
Killian PH, Kronski E, Michalik KM, Barbieri O, Astigiano S, Sommerhoff CP, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and-2. Carcinogenesis. 2012;33(12):2507-19.
https://doi.org/10.1093/carcin/bgs312
PMid:23042094
Singh S, Aggarwal BB. Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane). J Biol Chem. 1995;270(42):24995-5000.
https://doi.org/10.1074/jbc.270.42.24995
PMid:7559628
Jobin C, Bradham CA, Russo MP, Juma B, Narula AS, Brenner DA, et al. Curcumin blocks cytokine-mediated NF-κB activation and proinflammatory gene expression by inhibiting inhibitory factor I-κB kinase activity. J Immunol. 1999;163(6):3474-83.
Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-κB and IκBα kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood. 2003;101(3):1053-62.
https://doi.org/10.1182/blood-2002-05-1320
PMid:12393461
Piccolella M, Crippa V, Messi E, Tetel MJ, Poletti A. Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells. Pharmacol. Res.. 2014;79:13-20.
https://doi.org/10.1016/j.phrs.2013.10.002
PMid:24184124
Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004;25(2):276-308.
https://doi.org/10.1210/er.2002-0032
PMid:15082523
Richter E, Srivastava S, Dobi A. Androgen receptor and prostate cancer. Prostate Cancer Prostatic Dis. 2007;10(2):114-8.
https://doi.org/10.1038/sj.pcan.4500936
PMid:17297502
Aggarwal BB. Prostate cancer and curcumin: add spice to your life. Cancer Biol Ther. 2008;7(9):1436-40.
https://doi.org/10.4161/cbt.7.9.6659
PMid:18769126
Sharma R, Gescher A, Steward W. Curcumin: the story so far. Eur J Cancer. 2005;41(13):1955-68.
https://doi.org/10.1016/j.ejca.2005.05.009
PMid:16081279
Banerjee S, Singh SK, Chowdhury I, Lillard Jr JW, Singh R. Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer. Front Biosci. 2017;9:235.
https://doi.org/10.2741/e798
PMid:28199187
Li J, Xiang S, Zhang Q, Wu J, Tang Q, Zhou J, et al. Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C. J Exp Clin Cancer Res. 2015;34(1):1-11.
https://doi.org/10.1186/s13046-015-0168-z
PMid:25971429 PMCid:PMC4446835
Sharma V, Kumar L, Mohanty SK, Maikhuri JP, Rajender S, Gupta G. Sensitization of androgen refractory prostate cancer cells to anti-androgens through re-expression of epigenetically repressed androgen receptor-synergistic action of quercetin and curcumin. Mol Cell Endocrinol. 2016;431:12-23.
https://doi.org/10.1016/j.mce.2016.04.024
PMid:27132804
Wang R, Sun Y, Li L, Niu Y, Lin W, Lin C, et al. Preclinical study using Malat1 small interfering RNA or androgen receptor splicing variant 7 degradation enhancer ASC-J9® to suppress enzalutamide-resistant prostate cancer progression. Eur Urol. 2017;72(5):835-44.
https://doi.org/10.1016/j.eururo.2017.04.005
PMid:28528814 PMCid:PMC5802348
Tsui KH, Feng TH, Lin CM, Chang PL, Juang HH. Curcumin blocks the activation of androgen and interlukin‐6 on prostate‐specific antigen expression in human prostatic carcinoma cells. J. Androl.. 2008;29(6):661-8.
https://doi.org/10.2164/jandrol.108.004911
PMid:18676361
Choi HY, Lim J, Hong JH. Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis. 2010;13(4):343-9.
https://doi.org/10.1038/pcan.2010.26
PMid:20680030
Dorai T, Gehani N, Katz A. Therapeutic potential of curcumin in human prostate cancer-I. Curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Prostate Cancer Prostatic Dis. 2000;3(2):84-93.
https://doi.org/10.1038/sj.pcan.4500399
PMid:12497104
García-Aranda M, Redondo M. Protein kinase targets in breast cancer. Int J Mol Sci. 2017;18(12):2543.
https://doi.org/10.3390/ijms18122543
PMid:29186886 PMCid:PMC5751146
Anderson WF, Chatterjee N, Ershler WB, Brawley OW. Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat. 2002;76(1):27-36.
https://doi.org/10.1023/A:1020299707510
PMid:12408373
Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. PNAS. 2001;98(19):10869-74.
https://doi.org/10.1073/pnas.191367098
PMid:11553815 PMCid:PMC58566
Aceto N, Sausgruber N, Brinkhaus H, Gaidatzis D, Martiny-Baron G, Mazzarol G, et al. Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop. Nat Med. 2012;18(4):529.
https://doi.org/10.1038/nm.2645
PMid:22388088
Jason CY, Formenti SC. Integration of radiation and immunotherapy in breast cancer-Treatment implications. The Breast. 2018;38:66-74.
https://doi.org/10.1016/j.breast.2017.12.005
PMid:29253718
Song X, Zhang M, Dai E, Luo Y. Molecular targets of curcumin in breast cancer. Mol. Med. Rep. 2019;19(1):23-9.
https://doi.org/10.3892/mmr.2018.9665
Nejati-Koshki K, Akbarzadeh A, Pourhassan-Moghaddam M. Curcumin inhibits leptin gene expression and secretion in breast cancer cells by estrogen receptors. Cancer Cell Int. 2014;14(1):1-7.
https://doi.org/10.1186/1475-2867-14-66
PMid:25866478 PMCid:PMC4392783
Hallman K, Aleck K, Dwyer B, Lloyd V, Quigley M, Sitto N, et al. The effects of turmeric (curcumin) on tumor suppressor protein (p53) and estrogen receptor (ERα) in breast cancer cells. Breast Cancer (London). 2017;9:153.
https://doi.org/10.2147/BCTT.S125783
PMid:28331366 PMCid:PMC5354546
Lai H-W, Chien S-Y, Kuo S-J, Tseng L-M, Lin H-Y, Chi C-W, et al. The potential utility of curcumin in the treatment of HER-2-overexpressed breast cancer: an in vitro and in vivo comparison study with herceptin. Evid Based Complement Alternat Med. 2012;2012.
https://doi.org/10.1155/2012/486568
PMid:21876713 PMCid:PMC3162976
Verma SP, Salamone E, Goldin B. Curcumin and genistein, plant natural products, show synergistic inhibitory effects on the growth of human breast cancer MCF-7 cells induced by estrogenic pesticides. Biochem Biophys Res Commun. 1997;233(3):692-6.
https://doi.org/10.1006/bbrc.1997.6527
PMid:9168916
Karunagaran D, Rashmi R, Kumar T. Induction of apoptosis by curcumin and its implications for cancer therapy. Curr Cancer Drug Targets. 2005;5(2):117-29.
https://doi.org/10.2174/1568009053202081
PMid:15810876
Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? The AAPS journal. 2009;11(3):495-510.
https://doi.org/10.1208/s12248-009-9128-x
PMid:19590964 PMCid:PMC2758121
Sikora E, Bielak-Żmijewska A, Magalska A, Piwocka K, Mosieniak G, Kalinowska M, et al. Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells. Mol Cancer Ther. 2006;5(4):927-34.
https://doi.org/10.1158/1535-7163.MCT-05-0360
PMid:16648563
Shehzad A, Qureshi M, Anwar MN, Lee YS. Multifunctional curcumin mediate multitherapeutic effects. J Food Sci. 2017;82(9):2006-15.
https://doi.org/10.1111/1750-3841.13793
PMid:28771714
Arablou T, Kolahdouz-Mohammadi R. Curcumin and endometriosis: Review on potential roles and molecular mechanisms. Biomed Pharmacother. 2018;97:91-7.
https://doi.org/10.1016/j.biopha.2017.10.119
PMid:29080464
Sahin K, Orhan C, Tuzcu M, Sahin N, Tastan H, Özercan İH, et al. Chemopreventive and antitumor efficacy of curcumin in a spontaneously developing hen ovarian cancer model. Cancer Prev Res 2018;11(1):59-67.
https://doi.org/10.1158/1940-6207.CAPR-16-0289
PMid:29089332
McClay EF, Albright KD, Jones JA, Eastman A, Christen R, Howell SB. Modulation of cisplatin resistance in human malignant melanoma cells. Cancer Res. 1992;52(24):6790-6.
Mc Clay EF, Albright KD, Jones JA, Christen RD, Howell SB. Tamoxifen modulation of cisplatin sensitivity in human malignant melanoma cells. Cancer Res. 1993;53(7):1571-6.
Bast RC, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nature Reviews Cancer. 2009;9(6):415-28.
https://doi.org/10.1038/nrc2644
PMid:19461667 PMCid:PMC2814299
Vaughan S, Coward JI, Bast RC, Berchuck A, Berek JS, Brenton JD, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat. Rev. Cancer. 2011;11(10):719-25.
https://doi.org/10.1038/nrc3144
PMid:21941283 PMCid:PMC3380637
Stewart C, Ralyea C, Lockwood S, editors. Ovarian cancer: an integrated review. Seminars in oncology nursing; 2019: Elsevier.
https://doi.org/10.1016/j.soncn.2019.02.001
PMid:30867104
Shi M, Cai Q, Yao L, Mao Y, Ming Y, Ouyang G. Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int. 2006;30(3):221-6.
https://doi.org/10.1016/j.cellbi.2005.10.024
PMid:16376585
Weir NM, Selvendiran K, Kutala VK, Tong L, Vishwanath S, Rajaram M et al. Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol Ther. 2007;6(2):178-84.
https://doi.org/10.4161/cbt.6.2.3577
PMid:17218783 PMCid:PMC1852522
Yen H-Y, Tsao C-W, Lin Y-W, Kuo C-C, Tsao C-H, Liu C-Y. 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
Chock KL, Allison JM, Shimizu Y, ElShamy WM. BRCA1-IRIS overexpression promotes cisplatin resistance in ovarian cancer cells. Cancer Res. 2010;70(21):8782-91.
https://doi.org/10.1158/0008-5472.CAN-10-1352
PMid:20940403
K Tiwari A, Sodani K, Dai C-L, R Ashby C, Chen Z-S. Revisiting the ABCs of multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol. 2011;12(4):570-94.
https://doi.org/10.2174/138920111795164048
PMid:21118094
Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway. Clin Cancer Res. 2007;13(11):3423-30.
https://doi.org/10.1158/1078-0432.CCR-06-3072
PMid:17545551
Ganta S, Amiji M. Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm. 2009;6(3):928-39.
https://doi.org/10.1021/mp800240j
PMid:19278222

Copyright (c) 2021 Galen Medical Journal

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).