In vitro selective cytotoxicity of the dietary chalcone cardamonin (CD) on melanoma compared to healthy cells is mediated by apoptosis

Autoři: Lena Berning aff001;  Lisa Scharf aff001;  Elif Aplak aff001;  David Stucki aff001;  Claudia von Montfort aff001;  Andreas S. Reichert aff001;  Wilhelm Stahl aff001;  Peter Brenneisen aff001
Působiště autorů: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany aff001
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222267


Malignant melanoma is an aggressive type of cancer and the deadliest form of skin cancer. Even though enormous efforts have been undertaken, in particular the treatment options against the metastasizing form are challenging and the prognosis is generally poor. A novel therapeutical approach is the application of secondary plant constituents occurring in food and food products. Herein, the effect of the dietary chalcone cardamonin, inter alia found in Alpinia species, was tested using human malignant melanoma cells. These data were compared to cardamonin treated normal melanocytes and dermal fibroblasts representing healthy cells. To investigate the impact of cardamonin on tumor and normal cells, it was added to monolayer cell cultures and cytotoxicity, proliferation, tumor invasion, and apoptosis were studied with appropriate cell biological and biochemical methods. Cardamonin treatment resulted in an apoptosis-mediated increase in cytotoxicity towards tumor cells, a decrease in their proliferation rate, and a lowered invasive capacity, whereas the viability of melanocytes and fibroblasts was hardly affected at such concentrations. A selective cytotoxic effect of cardamonin on melanoma cells compared to normal (healthy) cells was shown in vitro. This study along with others highlights that dietary chalcones may be a valuable tool in anticancer therapies which has to be proven in the future in vivo.

Klíčová slova:

Apoptosis – Cancer treatment – Cytotoxicity – Fibroblasts – MTT assay – Melanoma cells – Melanocytes – Melanomas


1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136: E359–E386. doi: 10.1002/ijc.29210 25220842

2. Shen W, Sakamoto N, Yang L. Melanoma-specific mortality and competing mortality in patients with non-metastatic malignant melanoma: a population-based analysis. BMC Cancer. 2016;16: 413. doi: 10.1186/s12885-016-2438-3 27389173

3. Matthews NH, Li W-Q, Qureshi AA, Weinstock MA, Cho E. Epidemiology of Melanoma. Cutan Melanoma Etiol Ther. Codon Publications; 2017. pp. 3–22. doi: 10.15586/codon.cutaneousmelanoma.2017.ch1 29461782

4. Dimitriou F, Krattinger R, Ramelyte E, Barysch MJ, Micaletto S, Dummer R, et al. The World of Melanoma: Epidemiologic, Genetic, and Anatomic Differences of Melanoma Across the Globe. Curr Oncol Rep. 2018;20: 87. doi: 10.1007/s11912-018-0732-8 30250984

5. Trucco LD, Mundra PA, Hogan K, Garcia-Martinez P, Viros A, Mandal AK, et al. Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma. Nat Med. 2019;25: 221–224. doi: 10.1038/s41591-018-0265-6 30510256

6. Emri G, Paragh G, Tósaki Á, Janka E, Kollár S, Hegedűs C, et al. Ultraviolet radiation-mediated development of cutaneous melanoma: An update. J Photochem Photobiol B Biol. 2018;185: 169–175. doi: 10.1016/j.jphotobiol.2018.06.005 29936410

7. Scharffetter-Kochanek K, Wlaschek M, Brenneisen P, Schauen M, Blaudschun R, Wenk J. UV-induced reactive oxygen species in photocarcinogenesis and photoaging. Biol Chem. 1997;378: 1247–1257. 9426184

8. Mohammadpour A, Derakhshan M, Darabi H, Hedayat P, Momeni M. Melanoma: Where we are and where we go. J Cell Physiol. 2019;234: 3307–3320. doi: 10.1002/jcp.27286 30362507

9. Malissen N, Grob J-J. Metastatic melanoma: recent therapeutic progress and future perspectives. Drugs. 2018;78: 1197–1209. doi: 10.1007/s40265-018-0945-z 30097888

10. Fujimura T, Hidaka T, Kambayashi Y, Aiba S. BRAF kinase inhibitors for treatment of melanoma: developments from early-stage animal studies to Phase II clinical trials. Expert Opin Investig Drugs. 2019;28: 143–148. doi: 10.1080/13543784.2019.1558442 30556435

11. Payandeh Z, Yarahmadi M, Nariman‐Saleh‐Fam Z, Tarhriz V, Islami M, Aghdam AM, et al. Immune therapy of melanoma: Overview of therapeutic vaccines. J Cell Physiol. 2019; jcp.28181. doi: 10.1002/jcp.28181 30706472

12. Pesic M, Podolski-Renic A, Stojkovic S, Matovic B, Zmejkoski D, Kojic V, et al. Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. Chem Biol Interact. 2015;232: 85–93. doi: 10.1016/j.cbi.2015.03.013 25813935

13. Alili L, Sack M, von Montfort C, Giri S, Das S, Carroll KS, et al. Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxid Redox Signal. 2013;19: 765–778. doi: 10.1089/ars.2012.4831 23198807

14. Brenneisen P, Reichert A. Nanotherapy and reactive oxygen species (ROS) in cancer: a novel perspective. Antioxidants. 2018;7: 31. doi: 10.3390/antiox7020031 29470419

15. Atkinson V. Medical management of malignant melanoma. Aust Prescr. 2015;38: 74–78. doi: 10.18773/austprescr.2015.028 26648623

16. Rajanna S, Rastogi I, Wojdyla L, Furo H, Kulesza A, Lin L, et al. Current molecularly targeting therapies in NSCLC and melanoma. Anticancer Agents Med Chem. 2015;15: 856–868. doi: 10.2174/1871520615666150202100130 25642982

17. Edwardson D, Narendrula R, Chewchuk S, Mispel-Beyer K, Mapletoft J, Parissenti A.Role of drug metabolism in the cytotoxicity and clinical efficacy of anthracyclines. Curr Drug Metab. 2015;16: 412–426. doi: 10.2174/1389200216888150915112039 26321196

18. Kamb A, Wee S, Lengauer C. Why is cancer drug discovery so difficult? Nat Rev Drug Discov. 2007;6: 115–120. doi: 10.1038/nrd2155 17159925

19. Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S, et al. A case-control study of gastric cancer and diet in Italy. Int J Cancer. 1989;44: 611–616. doi: 10.1002/ijc.2910440409 2793233

20. Kaefer CM, Milner JA. The role of herbs and spices in cancer prevention. J Nutr Biochem. 2008;19: 347–361. doi: 10.1016/j.jnutbio.2007.11.003 18499033

21. Orlikova B, Tasdemir D, Golais F, Dicato M, Diederich M. Dietary chalcones with chemopreventive and chemotherapeutic potential. Genes Nutr. 2011;6: 125–147. doi: 10.1007/s12263-011-0210-5 21484163

22. Edwards ML, Stemerick DM, Sunkara PS. Chalcones: A new class of antimitotic agents. J Med Chem. 1990;33: 1948–1954. doi: 10.1021/jm00169a021 2362275

23. Navarini ALF, Chiaradia LD, Mascarello A, Fritzen M, Nunes RJ, Yunes RA, et al. Hydroxychalcones induce apoptosis in B16-F10 melanoma cells via GSH and ATP depletion. Eur J Med Chem. 2009;44: 1630–1637. doi: 10.1016/j.ejmech.2008.09.009 19211173

24. Su Y, Huang W-C, Lee W-H, Bamodu OA, Zucha MA, Astuti I, et al. Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication. Tumor Biol. 2017;39: 101042831769168. doi: 10.1177/1010428317691689 28466786

25. Henmi K, Hiwatashi Y, Hikita E, Toyama N, Hirano T. Methoxy- and fluoro-chalcone derivatives arrest cell cycle progression and induce apoptosis in human melanoma cell A375. Biol Pharm Bull. 2009;32: 1109–1113. doi: 10.1248/bpb.32.1109 19483325

26. Ahmed FF, Abd El-Hafeez AA, Abbas SH, Abdelhamid D, Abdel-Aziz M. New 1,2,4-triazole-chalcone hybrids induce caspase-3 dependent apoptosis in A549 human lung adenocarcinoma cells. Eur J Med Chem. 2018;151: 705–722. doi: 10.1016/j.ejmech.2018.03.073 29660690

27. Legette L, Karnpracha C, Reed RL, Choi J, Bobe G, Christensen JM, et al. Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops. Mol Nutr Food Res. 2014;58: 248–255. doi: 10.1002/mnfr.201300333 24038952

28. Liu M, Yin H, Qian X, Dong J, Qian Z, Miao J. Xanthohumol, a prenylated chalcone from hops, inhibits the viability and stemness of doxorubicin-resistant MCF-7/ADR Cells. Molecules. 2017;22: 36. doi: 10.3390/molecules22010036 28036030

29. Saito K, Matsuo Y, Imafuji H, Okubo T, Maeda Y, Sato T, et al. Xanthohumol inhibits angiogenesis by suppressing nuclear factor-kappaB activation in pancreatic cancer. Cancer Sci. 2018;109: 132–140. doi: 10.1111/cas.13441 29121426

30. Pan L, Becker H, Gerhäuser C. Xanthohumol induces apoptosis in cultured 40–16 human colon cancer cells by activation of the death receptor- and mitochondrial pathway. Mol Nutr Food Res. 2005;49: 837–843. doi: 10.1002/mnfr.200500065 15995977

31. Strathmann J, Klimo K, Sauer SW, Okun JG, Prehn JHM, Gerhäuser C. Xanthohumol-induced transient superoxide anion radical formation triggers cancer cells into apoptosis via a mitochondria-mediated mechanism. FASEB J. 2010;24: 2938–2950. doi: 10.1096/fj.10-155846 20335224

32. Jaiswal S, Shukla M, Sharma A, Rangaraj N, Vaghasiya K, Malik MY, et al. Preclinical pharmacokinetics and ADME characterization of a novel anticancer chalcone, cardamonin. Drug Test Anal. 2017;9: 1124–1136. doi: 10.1002/dta.2128 27794181

33. Goncalves LM, Valente IM, Rodrigues JA. An Overview on Cardamonin. J Med Food. 2014;17: 633–640. doi: 10.1089/jmf.2013.0061 24433078

34. Zhou X, Zhou R, Li Q, Jie X, Hong J, Zong Y, et al. Cardamonin inhibits the proliferation and metastasis of non-small-cell lung cancer cells by suppressing the PI3K/Akt/mTOR pathway. Anticancer Drugs. 2019; 1 [Epub ahead of print]. doi: 10.1097/CAD.0000000000000709 30640793

35. Shi D, Niu P, Heng X, Chen L, Zhu Y, Zhou J. Autophagy induced by cardamonin is associated with mTORC1 inhibition in SKOV3 cells. Pharmacol Reports. 2018;70: 908–916. doi: 10.1016/j.pharep.2018.04.005 30099297

36. Shrivastava S, Jeengar MK, Thummuri D, Koval A, Katanaev VL, Marepally S, et al. Cardamonin, a chalcone, inhibits human triple negative breast cancer cell invasiveness by downregulation of Wnt/ß-catenin signaling cascades and reversal of epithelial-mesenchymal transition. BioFactors. 2017;43: 152–169. doi: 10.1002/biof.1315 27580587

37. Zhang J, Sikka S, Siveen KS, Lee JH, Um J-Y, Kumar AP, et al. Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer. Apoptosis. 2017;22: 158–168. doi: 10.1007/s10495-016-1313-7 27900636

38. Wu N, Liu J, Zhao X, Yan Z, Jiang B, Wang L, et al. Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells. Tumor Biol. 2015;36: 9667–9676. doi: 10.1007/s13277-015-3673-y 26150336

39. Yadav VR, Prasad S, Aggarwal BB. Cardamonin sensitizes tumour cells to TRAIL through ROS- and CHOP-mediated up-regulation of death receptors and down-regulation of survival proteins. Br J Pharmacol. 2012;165: 741–753. doi: 10.1111/j.1476-5381.2011.01603.x 21797841

40. De Wever O, Mareel M. Role of myofibroblasts at the invasion front. Biol Chem. 2002;383: 55–67. doi: 10.1515/BC.2002.006 11928823

41. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65: 55–63. doi: 10.1016/0022-1759(83)90303-4 6606682

42. Maydt D, De Spirt S, Muschelknautz C, Stahl W, Müller TJJ. Chemical reactivity and biological activity of chalcones and other ?,ß-unsaturated carbonyl compounds. Xenobiotica. 2013;43: 711–718. doi: 10.3109/00498254.2012.754112 23339572

43. Laemmli UK. Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4. Nature. 1970;227: 680–685. doi: 10.1038/227680a0 5432063

44. Bopp SK, Lettieri T. Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrafish liver cell line. BMC Pharmacol. 2008;8: 8. doi: 10.1186/1471-2210-8-8 18513395

45. Banasiak D, Barnetson AR, Odell RA, Mameghan H, Russell PJ. Comparison between the clonogenic, MTT, and SRB assays for determining radiosensitivity in a panel of human bladder cancer cell lines and a ureteral cell line. Radiat Oncol Investig. 1999;7: 77–85. doi: 10.1002/(SICI)1520-6823(1999)7:2<77::AID-ROI3>3.0.CO;2-M 10333248

46. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, et al. New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening. JNCI J Natl Cancer Inst. 1990;82: 1107–1112. doi: 10.1093/jnci/82.13.1107 2359136

47. Lyles RH, Poindexter C, Evans A, Brown M, Cooper CR. Nonlinear model-based estimates of IC50 for studies involving continuous therapeutic dose-response data. Contemp Clin Trials. 2008;29: 878–886. doi: 10.1016/j.cct.2008.05.009 18582601

48. Angi M, Kalirai H, Prendergast S, Simpson D, Hammond DE, Madigan MC, et al. In-depth proteomic profiling of the uveal melanoma secretome. Oncotarget. 2016;7: 49623–49635. doi: 10.18632/oncotarget.10418 27391064

49. Csala M, Kardon T, Legeza B, Lizak B, Mandl J, Margittai E, et al. On the role of 4-hydroxynonenal in health and disease. Biochim Biophys Acta—Mol Basis Dis. 2015;1852: 826–838. doi: 10.1016/j.bbadis.2015.01.015 25643868

50. Zheng Y, Begum S, Zhang C, Fleming K, Masumura C, Zhang M, et al. Increased BrdU incorporation reflecting DNA repair, neuronal de-differentiation or possible neurogenesis in the adult cochlear nucleus following bilateral cochlear lesions in the rat. Exp Brain Res. 2011;210: 477–487. doi: 10.1007/s00221-010-2491-0 21104237

51. Rubbi CP, Milner J. Analysis of nucleotide excision repair by detection of single-stranded DNA transients. Carcinogenesis. 2001;22: 1789–1796. doi: 10.1093/carcin/22.11.1789 11698340

52. Zhang J, Gelman IH, Katsuta E, Liang Y, Wang X, Li J, et al. Glucose Drives Growth factor-independent esophageal cancer proliferation via phosphohistidine-focal adhesion kinase signaling. Cell Mol Gastroenterol Hepatol. 2019;8: 37–60. doi: 10.1016/j.jcmgh.2019.02.009 30836148

53. Ferguson J, Smith M, Zudaire I, Wellbrock C, Arozarena I. Glucose availability controls ATF4-mediated MITF suppression to drive melanoma cell growth. Oncotarget. 2017;8: 32946–32959. doi: 10.18632/oncotarget.16514 28380427

54. Tan B, Liu H, He G, Xiao H, Xiao D, Liu Y, et al. Alanyl-glutamine but not glycyl-glutamine improved the proliferation of enterocytes as glutamine substitution in vitro. Amino Acids. 2017;49: 2023–2031. doi: 10.1007/s00726-017-2460-z 28861626

55. Roth E, Ollenschlager G, Hamilton G, Simmel A, Langer K, Fekl W, et al. Influence of two glutamine-containing dipeptides on growth of mammalian cells. Vitr Cell Dev Biol. 1988;24: 696–698. doi: 10.1007/BF02623607

56. Yun C, Lee S. The roles of autophagy in cancer. Int J Mol Sci. 2018;19: 3466. doi: 10.3390/ijms19113466 30400561

57. Sack-Zschauer M, Karaman-Aplak E, Wyrich C, Das S, Schubert T, Meyer H, et al. Efficacy of dfferent compositions of cerium oxide nanoparticles in tumor-stroma interaction. J Biomed Nanotechnol. 2017;13: 1735–1746. doi: 10.1166/jbn.2017.2452 29490761

58. Niemeyer ED, Brodbelt JS. Regiospecificity of Human UDP-glucuronosyltransferase Isoforms in Chalcone and Flavanone Glucuronidation Determined by Metal Complexation and Tandem Mass Spectrometry. J Nat Prod. 2013;76: 1121–1132. doi: 10.1021/np400195z 23713759

59. Matsushima R, Kageyama H. Photochemical cyclization of 2'-hydroxychalcones. J Chem Soc, Perkin Trans 2. The Royal Society of Chemistry; 1985; 743–748. doi: 10.1039/P29850000743

60. Sack M, Alili L, Karaman E, Das S, Gupta A, Seal S, et al. Combination of conventional chemotherapeutics with redox-active cerium oxide nanoparticles-a novel aspect in cancer therapy. Mol Cancer Ther. 2014;13: 1740–1749. doi: 10.1158/1535-7163.MCT-13-0950 24825856

61. Liao N-C, Shih Y-L, Chou J-S, Chen K-W, Chen Y-L, Lee M-H, et al. Cardamonin induces cell cycle arrest, apoptosis and alters apoptosis associated gene expression in WEHI-3 mouse leukemia cells. Am J Chin Med. 2019;47: 635–656. doi: 10.1142/S0192415X19500332 31023073

62. Wang Y, Ma J, Yan X, Chen X, Si L, Liu Y, et al. Isoliquiritigenin inhibits proliferation and induces apoptosis via alleviating hypoxia and reducing glycolysis in mouse melanoma B16F10 cells. Recent Pat Anticancer Drug Discov. 2016;11: 215–227. doi: 10.2174/1573406412666160307151904 26951491

63. Zhang Y, Dai M, Yuan Z. Methods for the detection of reactive oxygen species. Anal Methods. 2018;10: 4625–4638. doi: 10.1039/C8AY01339J

64. Kim M-S, Lee J, Lee K-M, Yang S-H, Sujinna Choi, Chung S-Y, et al. Involvement of hydrogen peroxide in mistletoe lectin-II-induced apoptosis of myeloleukemic U937 cells. Life Sci. 2003;73: 1231–1243. doi: 10.1016/s0024-3205(03)00418-1 12850239

65. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader11Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee by the United States Department of Agriculture and does not imp. Free Radic Biol Med. 1999;27: 612–616. doi: 10.1016/s0891-5849(99)00107-0 10490282

66. Wang X, Roper MG. Measurement of DCF fluorescence as a measure of reactive oxygen species in murine islets of Langerhans. Anal Methods. 2014;6: 3019–3024. doi: 10.1039/C4AY00288A 24955137

67. Tetz LM, Kamau PW, Cheng AA, Meeker JD, Loch-Caruso R. Troubleshooting the dichlorofluorescein assay to avoid artifacts in measurement of toxicant-stimulated cellular production of reactive oxidant species. J Pharmacol Toxicol Methods. 2013;67: 56–60. doi: 10.1016/j.vascn.2013.01.195 23380227

68. Cui X. Reactive oxygen species: the achilles-heel of cancer cells? Antioxid Redox Signal. 2012;16: 1212–1214. doi: 10.1089/ars.2012.4532 22304673

69. Liu J, Wang Z. Increased oxidative stress as a selective anticancer therapy. Oxid Med Cell Longev. 2015;2015: 1–12. doi: 10.1155/2015/294303 26273420

70. Ajiboye TO, Yakubu MT, Oladiji AT. Electrophilic and reactive oxygen species detoxification potentials of chalcone dimers is mediated by redox transcription factor Nrf-2. J Biochem Mol Toxicol. 2014;28: 11–22. doi: 10.1002/jbt.21517 23963778

71. Skrzypek K, Tertil M, Golda S, Ciesla M, Weglarczyk K, Collet G, et al. Interplay between heme oxygenase-1 and miR-378 affects non-small cell lung carcinoma growth, vascularization, and metastasis. Antioxid Redox Signal. 2013;19: 644–660. doi: 10.1089/ars.2013.5184 23617628

72. Zou C, Zou C, Cheng W, Li Q, Han Z, Wang X, et al. Heme oxygenase-1 retards hepatocellular carcinoma progression through the microRNA pathway. Oncol Rep. 2016;36: 2715–2722. doi: 10.3892/or.2016.5056 27571925

73. Gandini NA, Alonso EN, Fermento ME, Mascaro M, Abba MC, Colo GP, et al. Heme Oxygenase-1 has an antitumor role in breast cancer. Antioxid Redox Signal. 2019;30: 2030–2049. doi: 10.1089/ars.2018.7554 30484334

74. Wang Z, Wang N, Han S, Wang D, Mo S, Yu L, et al. Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via VEGF/VEGFR-2 signaling pathway. Pizzo S V, editor. PLoS One. 2013;8: e68566. doi: 10.1371/journal.pone.0068566 23861918

75. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35: 495–516. doi: 10.1080/01926230701320337 17562483

76. Chen T, Wong YS. Selenocystine induces apoptosis of A375 human melanoma cells by activating ROS-mediated mitochondrial pathway and p53 phosphorylation. Cell Mol Life Sci. 2008;65: 2763–2775. doi: 10.1007/s00018-008-8329-2 18661100

77. Zhang Y, Chen X, Gueydan C, Han J. Plasma membrane changes during programmed cell deaths. Cell Res. 2018;28: 9–21. doi: 10.1038/cr.2017.133 29076500

78. Herceg Z, Wang Z-Q. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res Mol Mech Mutagen. 2001;477: 97–110. doi: 10.1016/S0027-5107(01)00111-7

79. Bieche I, Pennaneach V, Driouch K, Vacher S, Zaremba T, Susini A, et al. Variations in the mRNA expression of poly(ADP-ribose) polymerases, poly(ADP-ribose) glycohydrolase and ADP-ribosylhydrolase 3 in breast tumors and impact on clinical outcome. Int J Cancer. 2013;133: 2791–2800. doi: 10.1002/ijc.28304 23736962

80. Liu Y, Zhang Y, Zhao Y, Gao D, Xing J, Liu H. High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer. Oncol Lett. 2016;12: 3825–3835. doi: 10.3892/ol.2016.5169 27895737

81. Pashaiefar H, Yaghmaie M, Tavakkoly-Bazzaz J, Ghaffari SH, Alimoghaddam K, Momeny M, et al. PARP-1 Overexpression as an independent prognostic factor in adult non-M3 acute myeloid leukemia. Genet Test Mol Biomarkers. 2018;22: 343–349. doi: 10.1089/gtmb.2018.0085 29812960

82. Prasad CB, Prasad SB, Yadav SS, Pandey LK, Singh S, Pradhan S, et al. Olaparib modulates DNA repair efficiency, sensitizes cervical cancer cells to cisplatin and exhibits anti-metastatic property. Sci Rep. 2017;7: 12876. doi: 10.1038/s41598-017-13232-3 28993682

83. Dörsam B, Seiwert N, Foersch S, Stroh S, Nagel G, Begaliew D, et al. PARP-1 protects against colorectal tumor induction, but promotes inflammation-driven colorectal tumor progression. Proc Natl Acad Sci. 2018;115: E4061–E4070. doi: 10.1073/pnas.1712345115 29632181

84. Tarhini A, Kudchadkar RR. Predictive and on-treatment monitoring biomarkers in advanced melanoma: moving toward personalized medicine. Cancer Treat Rev. 2018;71: 8–18. doi: 10.1016/j.ctrv.2018.09.005 30273812

85. Kwong LN, Davies MA. Targeted therapy for melanoma: rational combinatorial approaches. Oncogene. 2014;33: 1–9. doi: 10.1038/onc.2013.34 23416974

86. Peterson GM, Thomas J, Yee KC, Kosari S, Naunton M, Olesen IH. Monoclonal antibody therapy in cancer: when two is better (and considerably more expensive) than one. J Clin Pharm Ther. 2018;43: 925–930. doi: 10.1111/jcpt.12750 30047144

87. Aghajanpour M, Nazer MR, Obeidavi Z, Akbari M, Ezati P, Kor NM. Functional foods and their role in cancer prevention and health promotion: a comprehensive review. American Journal of Cancer Research. 2017. pp. 740–769. 28469951

88. Kuno T, Tsukamoto T, Hara A, Tanaka T. Cancer chemoprevention through the induction of apoptosis by natural compounds. J Biophys Chem. 2012;03: 156–173. doi: 10.4236/jbpc.2012.32018

89. Miura K, Green AC. Dietary Antioxidants and Melanoma: Evidence from Cohort and Intervention Studies. Nutr Cancer. 2015;67: 867–876. doi: 10.1080/01635581.2015.1053499 26147450

90. Krajnovic T, Kalucrossed D Signerovic GN, Wessjohann LA, Mijatovic S, Maksimovic-Ivanic D. Versatile antitumor potential of isoxanthohumol: Enhancement of paclitaxel activity in vivo. Pharmacol Res. 2016;105: 62–73. doi: 10.1016/j.phrs.2016.01.011 26784390

91. Gasparovic AC, Milkovic L, Sunjic SB, Zarkovic N. Cancer growth regulation by 4-hydroxynonenal. Free Radic Biol Med. 2017;111: 226–234. doi: 10.1016/j.freeradbiomed.2017.01.030 28131901

92. Kreuzer T, Zarkovic N, Grube R, Schaur RJ. Inhibition of HeLa Cell Proliferation by 4-hydroxynonenal is associated with enhanced expression of the c-fos oncogene. Cancer Biother Radiopharm. 1997;12: 131–136. doi: 10.1089/cbr.1997.12.131 10851457

93. Pizzimenti S, Ciamporcero E, Pettazzoni P, Osella-Abate S, Novelli M, Toaldo C, et al. The inclusion complex of 4-hydroxynonenal with a polymeric derivative of ß-cyclodextrin enhances the antitumoral efficacy of the aldehyde in several tumor cell lines and in a three-dimensional human melanoma model. Free Radic Biol Med. 2013;65: 765–777. doi: 10.1016/j.freeradbiomed.2013.06.035 23811007

94. Wolff H, Motyl M, Hellerbrand C, Heilmann J, Kraus B. Xanthohumol uptake and intracellular kinetics in hepatocytes, hepatic stellate cells, and intestinal cells. J Agric Food Chem. 2011;59: 12893–12901. doi: 10.1021/jf203689z 22088086

95. De Spirt S, Eckers A, Wehrend C, Micoogullari M, Sies H, Stahl W, et al. Interplay between the chalcone cardamonin and selenium in the biosynthesis of Nrf2-regulated antioxidant enzymes in intestinal Caco-2 cells. Free Radic Biol Med. 2016;91: 164–171. doi: 10.1016/j.freeradbiomed.2015.12.011 26698667

96. Loboda A, Jozkowicz A, Dulak J. HO-1/CO system in tumor growth, angiogenesis and metabolism—Targeting HO-1 as an anti-tumor therapy. Vascul Pharmacol. 2015;74: 11–22. doi: 10.1016/j.vph.2015.09.004 26392237

97. Was H, Dulak J, Jozkowicz A. Heme oxygenase-1 in tumor biology and therapy. Curr Drug Targets. 2010;11: 1551–1570. doi: 10.2174/1389450111009011551 20704546

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