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Reviews of Physiology, Biochemistry and Pharmacology 176 pp 107–129Cite as

Curcumin in Advancing Treatment for Gynecological Cancers with Developed Drug- and Radiotherapy-Associated Resistance

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Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 176))

Abstract

The development of resistance toward current cancer therapy modalities is an ongoing challenge in gynecological cancers, especially ovarian and cervical malignancies that require further investigations in the context of drug- and irradiation-induced resistance. In this regard, curcumin has demonstrated beneficial and highly pleiotropic actions and increased the therapeutic efficiency of radiochemotherapy. The antiproliferative, anti-metastatic, anti-angiogenic, and anti-inflammatory effects of curcumin have been extensively reported in the literature, and it could also act as a chemopreventive agent which mitigates the out-of-target harmful impact of chemotherapeutics on surrounding normal tissues. The current review discussed the modulating influences of curcumin on some cell and molecular features, including the cell signaling and molecular pathways altered upon curcumin treatment, the expression of target genes involved in the progression of gynecological cancers, as well as the expression of genes accountable for the development of resistance toward common chemotherapeutics and radiotherapy. The cell molecular targets implicated in curcumin’s resensitizing effect, when used together with cisplatin, paclitaxel, and irradiation in gynecological cancers, are also addressed. Finally, rational approaches for improving the therapeutic benefits of curcumin, including curcumin derivatives with enhanced therapeutic efficacy, using nanoformulations to advance curcumin stability in physiological media and improve bioavailability have been elucidated.

The original version of this chapter was revised. A correction to this chapter is available at DOI: 10.1007/112_2018_14.

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Change history

  • 08 December 2018

    The affiliation of the 6th author Dr. Abolfazl Mehdizadehkashi was incorrect. It has been corrected to Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran.

Abbreviations

CDK:

Cyclin-dependent kinase

COX-2:

Cyclooxygenase-2

Cur:

Curcumin

DNMTs:

DNA methyltransferases

GSTs:

Glutathione S-transferases

HDAC:

Histone deacetylases

IAPs:

Inhibitor of apoptosis family of proteins

ICAM-1:

Intercellular adhesion molecule 1

IKK:

IκB kinase

iNOS:

Inducible nitric oxide synthase

MT:

Metallothionein

P-gp:

P-glycoprotein

PI3K:

Phosphatidylinositide 3-kinase

VEGF:

Vascular endothelial growth factor

References

  • Abdollahi E, Momtazi AA, Johnston TP, Sahebkar A (2018) Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: a nature-made jack-of-all-trades? J Cell Physiol 233:830–848

    Article  CAS  Google Scholar 

  • Abouzeid AH, Patel NR, Sarisozen C, Torchilin VP (2014) Transferrin-targeted polymeric micelles co-loaded with curcumin and paclitaxel: efficient killing of paclitaxel-resistant cancer cells. Pharm Res 31:1938–1945

    Article  CAS  Google Scholar 

  • Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40–59

    Article  CAS  Google Scholar 

  • Ak T, Gülçin İ (2008) Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact 174:27–37

    Article  CAS  Google Scholar 

  • Aqil F, Munagala R, Jeyabalan J, Agrawal AK, Gupta R (2017) Exosomes for the enhanced tissue bioavailability and efficacy of curcumin. AAPS J 19:1691–1702

    Article  CAS  Google Scholar 

  • Bava SV, Puliappadamba VT, Deepti A, Nair A, Karunagaran D, Anto RJ (2005) Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-κB and the serine/threonine kinase Akt and is independent of tubulin polymerization. J Biol Chem 280:6301–6308

    Article  CAS  Google Scholar 

  • Chan MM, Fong D, Soprano KJ, Holmes WF, Heverling H (2003) Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J Cell Physiol 194:63–70

    Article  CAS  Google Scholar 

  • Chen P, Li J, Jiang H-G, Lan T, Chen Y-C (2015a) Curcumin reverses cisplatin resistance in cisplatin-resistant lung cancer cells by inhibiting FA/BRCA pathway. Tumor Biol 36:3591–3599

    Article  CAS  Google Scholar 

  • Chen Q, Gao Q, Chen K, Wang Y, Chen L, Li X (2015b) Curcumin suppresses migration and invasion of human endometrial carcinoma cells. Oncol Lett 10:1297–1302

    Article  CAS  Google Scholar 

  • Cheng SCS, Luo D, Xie Y (2001) Taxol induced BCL-2 protein phosphorylation in human hepatocellular carcinoma QGY-7703 cell line. Cell Biol Int 25:261–265

    Article  CAS  Google Scholar 

  • Debata PR, Castellanos MR, Fata JE, Baggett S, Rajupet S, Szerszen A, Begum S, Mata A, Murty VV, Opitz LM (2013) A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells. Gynecol Oncol 129:145–153

    Article  CAS  Google Scholar 

  • Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M, Diederich M (2005) Chemopreventive and therapeutic effects of curcumin. Cancer Lett 223:181–190

    Article  CAS  Google Scholar 

  • Ganta S, Amiji M (2009) Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm 6:928–939

    Article  CAS  Google Scholar 

  • Garcea G, Jones D, Singh R, Dennison A, Farmer P, Sharma R, Steward W, Gescher A, Berry D (2004) Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer 90:1011–1015

    Article  CAS  Google Scholar 

  • Giannakakou P, Sackett DL, Kang Y-K, Zhan Z, Buters JT, Fojo T, Poruchynsky MS (1997) Paclitaxel-resistant human ovarian cancer cells have mutant β-tubulins that exhibit impaired paclitaxel-driven polymerization. J Biol Chem 272:17118–17125

    Article  CAS  Google Scholar 

  • Hajavi J, Abbas Momtazi A, Johnston TP, Banach M, Majeed M, Sahebkar A (2017) Curcumin: a naturally occurring modulator of adipokines in diabetes. J Cell Biochem 118:4170–4182

    Article  CAS  Google Scholar 

  • Huq F, Yu JQ, Beale P, Chan C, Arzuman L, Nessa MU, Mazumder ME (2014) Combinations of platinums and selected phytochemicals as a means of overcoming resistance in ovarian cancer. Anticancer Res 34:541–545

    CAS  PubMed  Google Scholar 

  • Javvadi P, Segan AT, Tuttle SW, Koumenis C (2008) The chemopreventive agent curcumin is a potent radiosensitizer of human cervical tumor cells via increased reactive oxygen species production and overactivation of the mitogen-activated protein kinase pathway. Mol Pharmacol 73:1491–1501

    Article  CAS  Google Scholar 

  • Javvadi P, Hertan L, Kosoff R, Datta T, Kolev J, Mick R, Tuttle SW, Koumenis C (2010) Thioredoxin reductase-1 mediates curcumin-induced radiosensitization of squamous carcinoma cells. Cancer Res 70:1941–1950

    Article  CAS  Google Scholar 

  • Kasinski AL, Du Y, Thomas SL, Zhao J, Sun S-Y, Khuri FR, Wang C-Y, Shoji M, Sun A, Snyder JP (2008) Inhibition of IκB kinase-nuclear factor-κB signaling pathway by 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), a novel monoketone analog of curcumin. Mol Pharmacol 74:654–661

    Article  CAS  Google Scholar 

  • Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, Reddy BS (1999) Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res 59:597–601

    CAS  PubMed  Google Scholar 

  • Kumar SSD, Surianarayanan M, Vijayaraghavan R, Mandal AB, Macfarlane D (2014) Curcumin loaded poly (2-hydroxyethyl methacrylate) nanoparticles from gelled ionic liquid–In vitro cytotoxicity and anti-cancer activity in SKOV-3 cells. Eur J Pharm Sci 51:34–44

    Article  CAS  Google Scholar 

  • Kuttan G, Kumar KBH, Guruvayoorappan C, Kuttan R (2007) Antitumor, anti-invasion, and antimetastatic effects of curcumin. In: The molecular targets and therapeutic uses of curcumin in health and disease. Springer, Boston

    Google Scholar 

  • Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE (2006) Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 6:10

    Article  Google Scholar 

  • Li C, Ge X, Wang L (2017) Construction and comparison of different nanocarriers for co-delivery of cisplatin and curcumin: a synergistic combination nanotherapy for cervical cancer. Biomed Pharmacother 86:628–636

    Article  CAS  Google Scholar 

  • Liu Z, Zhu Y-Y, Li Z-Y, Ning S-Q (2016) Evaluation of the efficacy of paclitaxel with curcumin combination in ovarian cancer cells. Oncol Lett 12:3944–3948

    Article  CAS  Google Scholar 

  • Mancarella S, Greco V, Baldassarre F, Vergara D, Maffia M, Leporatti S (2015) Polymer-coated magnetic nanoparticles for curcumin delivery to cancer cells. Macromol Biosci 15:1365–1374

    Article  CAS  Google Scholar 

  • Maruthur NM, Bolen SD, Brancati FL, Clark JM (2009) The association of obesity and cervical cancer screening: a systematic review and meta-analysis. Obesity 17:375–381

    Article  Google Scholar 

  • Mishra S, Kapoor N, Ali AM, Pardhasaradhi B, Kumari AL, Khar A, Misra K (2005a) Differential apoptotic and redox regulatory activities of curcumin and its derivatives. Free Radic Biol Med 38:1353–1360

    Article  CAS  Google Scholar 

  • Mishra S, Narain U, Mishra R, Misra K (2005b) Design, development and synthesis of mixed bioconjugates of piperic acid–glycine, curcumin–glycine/alanine and curcumin–glycine–piperic acid and their antibacterial and antifungal properties. Bioorg Med Chem 13:1477–1486

    Article  CAS  Google Scholar 

  • Momtazi AA, Shahabipour F, Khatibi S, Johnston TP, Pirro M, Sahebkar A (2016) Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 171:1–38

    Article  CAS  Google Scholar 

  • Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili S-A, Johnston TP, Abdollahi E, Sahebkar A (2017) Curcumin: a natural modulator of immune cells in systemic lupus erythematosus. Autoimmun Rev 17:125–135

    Article  Google Scholar 

  • Montopoli M, Ragazzi E, Froldi G, Caparrotta L (2009) Cell-cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells. Cell Prolif 42:195–206

    Article  CAS  Google Scholar 

  • Nessa MU, Beale P, Chan C, Yu JQ, Huq F (2012) Studies on combination of platinum drugs cisplatin and oxaliplatin with phytochemicals anethole and curcumin in ovarian tumour models. Anticancer Res 32:4843–4850

    CAS  PubMed  Google Scholar 

  • Pan W, Yang H, Cao C, Song X, Wallin B, Kivlin R, Lu S, Hu G, Di W, Wan Y (2008) AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells. Oncol Rep 20:1553–1559

    CAS  PubMed  Google Scholar 

  • Panahi Y, Ahmadi Y, Teymouri M, Johnston TP, Sahebkar A (2018) Curcumin as a potential candidate for treating hyperlipidemia: a review of cellular and metabolic mechanisms. J Cell Physiol 233:141–152

    Article  CAS  Google Scholar 

  • Paulraj F, Abas F, Lajis NH, Othman I, Hassan SS, Naidu R (2015) The curcumin analogue 1, 5-bis (2-hydroxyphenyl)-1, 4-pentadiene-3-one induces apoptosis and downregulates E6 and E7 oncogene expression in HPV16 and HPV18-infected cervical cancer cells. Molecules 20:11830–11860

    Article  CAS  Google Scholar 

  • Peng S, Xu Q, Ling XB, Peng X, Du W, Chen L (2003) Molecular classification of cancer types from microarray data using the combination of genetic algorithms and support vector machines. FEBS Lett 555:358–362

    Article  CAS  Google Scholar 

  • Punfa W, Yodkeeree S, Pitchakarn P, Ampasavate C, Limtrakul P (2012) Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells. Acta Pharmacol Sin 33:823–831

    Article  CAS  Google Scholar 

  • Rezaee R, Momtazi AA, Monemi A, Sahebkar A (2016) Curcumin: a potentially powerful tool to reverse cisplatin-induced toxicity. Pharmacol Res 117:218–227

    Article  Google Scholar 

  • Roy M, Mukherjee S (2014) Reversal of resistance towards cisplatin by curcumin in cervical cancer cells. Asian Pac J Cancer Prev 15:1403–1410

    Article  Google Scholar 

  • Saengkrit N, Saesoo S, Srinuanchai W, Phunpee S, Ruktanonchai UR (2014) Influence of curcumin-loaded cationic liposome on anticancer activity for cervical cancer therapy. Colloids Surf B Biointerfaces 114:349–356

    Article  CAS  Google Scholar 

  • Sarisozen C, Abouzeid AH, Torchilin VP (2014) The effect of co-delivery of paclitaxel and curcumin by transferrin-targeted PEG-PE-based mixed micelles on resistant ovarian cancer in 3-D spheroids and in vivo tumors. Eur J Pharm Biopharm 88:539–550

    Article  CAS  Google Scholar 

  • Sharma R, Jadav SS, Yasmin S, Bhatia S, Khalilullah H, Ahsan MJ (2015) Simple, efficient, and improved synthesis of Biginelli-type compounds of curcumin as anticancer agents. Med Chem Res 24:636–644

    Article  CAS  Google Scholar 

  • Singh AK, Misra K (2013) Human papilloma virus 16 E6 protein as a target for curcuminoids, curcumin conjugates and congeners for chemoprevention of oral and cervical cancers. Interdiscip Sci Comput Life Sci 5:112

    Article  CAS  Google Scholar 

  • Soflaei S, Momtazi A, Majeed M, Derosa G, Maffioli P, Sahebkar A (2017) Curcumin: a natural pan-HDAC inhibitor in cancer. Curr Pharm Des 24:123–129

    Google Scholar 

  • Song Y-K, Kim C-K (2006) Topical delivery of low-molecular-weight heparin with surface-charged flexible liposomes. Biomaterials 27:271–280

    Article  CAS  Google Scholar 

  • Sreekanth C, Bava S, Sreekumar E, Anto R (2011) Molecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer. Oncogene 30:3139–3152

    Article  CAS  Google Scholar 

  • Tanaka Y, Kobayashi H, Suzuki M, Kanayama N, Terao T (2004) Transforming growth factor-β1-dependent urokinase up-regulation and promotion of invasion are involved in Src-MAPK-dependent signaling in human ovarian cancer cells. J Biol Chem 279:8567–8576

    Article  CAS  Google Scholar 

  • Teymouri M, Farzaneh H, Badiee A, Golmohammadzadeh S, Sadri K, Jaafari MR (2015) Investigation of Hexadecylphosphocholine (miltefosine) usage in Pegylated liposomal doxorubicin as a synergistic ingredient: in vitro and in vivo evaluation in mice bearing C26 colon carcinoma and B16F0 melanoma. Eur J Pharm Sci 80:66–73

    Article  CAS  Google Scholar 

  • Teymouri M, Badiee A, Golmohammadzadeh S, Sadri K, Akhtari J, Mellat M, Nikpoor AR, Jaafari MR (2016) Tat peptide and hexadecylphosphocholine introduction into pegylated liposomal doxorubicin: an in vitro and in vivo study on drug cellular delivery, release, biodistribution and antitumor activity. Int J Pharm 511:236–244

    Article  CAS  Google Scholar 

  • Teymouri M, Pirro M, Johnston TP, Sahebkar A (2017) Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: a review of chemistry, cellular, molecular, and preclinical features. Biofactors 43:331–346

    Article  CAS  Google Scholar 

  • Teymouri M, Barati N, Pirro M, Sahebkar A (2018) Biological and pharmacological evaluation of dimethoxycurcumin: a metabolically stable curcumin analogue with a promising therapeutic potential. J Cell Physiol 233:124–140

    Article  CAS  Google Scholar 

  • Wang W-M, Cheng H-C, Liu Y-C, Chang Y-L, Liu S-T (2011) Effect of dimethoxycurcumin beyond degradation of androgen receptor. Dermatol Sin 29:115–120

    Article  Google Scholar 

  • Watson JL, Greenshields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, Hoskin DW (2010) Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Mol Carcinog 49:13–24

    CAS  PubMed  Google Scholar 

  • Xu Y-Q, Chen W-R, Tsosie JK, Xie X, Li P, Wan J-B, He C-W, Chen M-W (2016) Niosome encapsulation of curcumin. J Nanomater 2016:15

    Google Scholar 

  • Yang YL, Ji C, Cheng L, He L, Lu CC, Wang R, Bi ZG (2012) Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells. Cancer Sci 103:1538–1545

    Article  CAS  Google Scholar 

  • Yunos NM, Beale P, Yu JQ, Huq F (2011) Synergism from sequenced combinations of curcumin and epigallocatechin-3-gallate with cisplatin in the killing of human ovarian cancer cells. Anticancer Res 31:1131–1140

    CAS  PubMed  Google Scholar 

  • Yusuf R, Duan Z, Lamendola D, Penson R, Seiden M (2003) Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation. Curr Cancer Drug Targets 3:1–19

    Article  CAS  Google Scholar 

  • Zaman MS, Chauhan N, Yallapu MM, Gara RK, Maher DM, Kumari S, Sikander M, Khan S, Zafar N, Jaggi M (2016) Curcumin nanoformulation for cervical cancer treatment. Sci Rep 6:20051

    Article  CAS  Google Scholar 

  • Zhang J, Liu J, Xu X, Li L (2017) Curcumin suppresses cisplatin resistance development partly via modulating extracellular vesicle-mediated transfer of MEG3 and miR-214 in ovarian cancer. Cancer Chemother Pharmacol 79:479–487

    Article  CAS  Google Scholar 

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Acknowledgment

The authors would like to say special thanks to Dr. Amir Saberi-Demneh and Dr. Leila Ghalichi for their guidance and kindness.

Conflict of Interest

The authors declare that they have no conflicts of interest about this report.

Author information

Authors and Affiliations

  1. Nanotechnology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Abbas Momtazi-Borojeni

  2. Department of Medical Biotechnology, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Abbas Momtazi-Borojeni

  3. Research Center of Advanced Technologies in Medicine, Torbat Heydarieh University of Medical Sciences, Torbat Heydarieh, Iran

    Jafar Mosafer

  4. Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran

    Banafsheh Nikfar

  5. Werlhof-Institut, Hannover, Germany

    Mahnaz Ekhlasi-Hundrieser

  6. Minimally Invasive Techniques Research Center in Women, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

    Shahla Chaichian

  7. Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran

    Abolfazl Mehdizadehkashi

  8. Department of Community Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Atefeh Vaezi

Authors
  1. Amir Abbas Momtazi-Borojeni
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  2. Jafar Mosafer
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  3. Banafsheh Nikfar
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  4. Mahnaz Ekhlasi-Hundrieser
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  5. Shahla Chaichian
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  6. Abolfazl Mehdizadehkashi
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  7. Atefeh Vaezi
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Corresponding authors

Correspondence to Amir Abbas Momtazi-Borojeni or Banafsheh Nikfar .

Editor information

Editors and Affiliations

  1. Heart Science Centre, The Magdi Yacoub Institute, Harefield, UK

    Pieter de Tombe

  2. Walther-Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians University of Munich, Munich, Germany

    Thomas Gudermann

  3. Department of Neurobiology , Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

    Reinhard Jahn

  4. Department of Cytobiology, University of Marburg, Marburg, Germany

    Roland Lill

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Momtazi-Borojeni, A.A. et al. (2018). Curcumin in Advancing Treatment for Gynecological Cancers with Developed Drug- and Radiotherapy-Associated Resistance. In: de Tombe, P., Gudermann, T., Jahn, R., Lill, R. (eds) Reviews of Physiology, Biochemistry and Pharmacology 176. Reviews of Physiology, Biochemistry and Pharmacology, vol 176. Springer, Cham. https://doi.org/10.1007/112_2018_11

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