Proteasome inhibition mediates p53 reactivation and anticancer activity of 6-Gingerol in cervical cancer cells

Oncotarget

Volumn 6, Issue 41, 2015, Pages 43310-43325

  Rastogi, Namrata ^a   Duggal, Shivali ^b   Singh, Shailendra Kumar ^c   Porwal, Konica ^a   Srivastava, Vikas Kumar ^b   Maurya, Rakesh ^a   Bhatt, M L B ^b   Mishra, Durga Prasad ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

^b KING GEORGE'S MEDICAL UNIVERSITY   (India)

^c OSAKA UNIVERSITY   (Japan)

Author keywords

6 Gingerol; Cervical cancer; Chromosome Section; HPV; P53 reactivation; Proteasome

Indexed keywords

(6) GINGEROL; BORTEZOMIB; CASPASE 3; CHYMOTRYPSIN; CISPLATIN; GINGER EXTRACT; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; ONCOPROTEIN; PROTEASOME; PROTEIN P21; PROTEIN P53; ANTINEOPLASTIC AGENT; CATECHOL DERIVATIVE; FATTY ALCOHOL; GINGEROL; SMALL INTERFERING RNA;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BODY WEIGHT; CANCER CELL; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; DNA DAMAGE; DRUG MECHANISM; DRUG POTENCY; FEMALE; G2 PHASE CELL CYCLE CHECKPOINT; GINGER; HEMATOLOGICAL PARAMETERS; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; M PHASE CELL CYCLE CHECKPOINT; MOLECULAR MECHANICS; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; TUMOR GROWTH; TUMOR VOLUME; TUMOR XENOGRAFT; UTERINE CERVIX CANCER; WART VIRUS; ANIMAL; COMPLICATION; CONFOCAL MICROSCOPY; DRUG EFFECTS; DRUG SCREENING; FLOW CYTOMETRY; GENETIC TRANSFECTION; HELA CELL LINE; MALE; METABOLISM; MOLECULAR DOCKING; MOUSE; NUDE MOUSE; PAPILLOMAVIRUS INFECTION; PATHOLOGY; REAL TIME POLYMERASE CHAIN REACTION; UTERINE CERVIX TUMOR; VIROLOGY; WESTERN BLOTTING;

ANIMALS; ANTINEOPLASTIC AGENTS; BLOTTING, WESTERN; CATECHOLS; CELL PROLIFERATION; FATTY ALCOHOLS; FEMALE; FLOW CYTOMETRY; HELA CELLS; HUMANS; MALE; MICE; MICE, NUDE; MICROSCOPY, CONFOCAL; MOLECULAR DOCKING SIMULATION; PAPILLOMAVIRUS INFECTIONS; PROTEASOME ENDOPEPTIDASE COMPLEX; REAL-TIME POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; TRANSFECTION; TUMOR SUPPRESSOR PROTEIN P53; UTERINE CERVICAL NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84952888940     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6383     Document Type: Article

References (61)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011:20; 61:69-90.
2. Sankaranarayanan R, Nene BM, Dinshaw K, Rajkumar R, Shastri S, Wesley R, Basu P, Sharma R, Thara S, Budukh A, Parkin DM. Early detection of cervical cancer with visual inspection methods: a summary of completed and on-going studies in India. SaludPublicaMex 45 Suppl 3; 2003:S399-407.
3. Bharti AC, Shukla S, Mahata S, Hedau S, Das BC.Antihuman papillomavirus therapeutics: facts & future. Indian J Med Res. 2009;130:296-310.
4. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders P J, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999:189:12-19.
5. Tan S. de Vries EG, van der Zee AG, de Jong S. Anticancer drugs aimed at E6 and E7 activity in HPV-positive cervical cancer. Curr Cancer Drug Targets. 2012;12:170-184.
6. Das BC, Hussain S, Nasare V, Bharadwaj M. Prospects and prejudices of human papillomavirus vaccines in India. Vaccine. 2008;26:2669-2679.
7. Serkies K, Jassem J. Concurrent weekly cisplatin and radiotherapy in routine management of cervical cancer: a report on patient compliance and acute toxicity. Int J RadiatOncolBiol Phys. 2004;60: 814-821.
8. Florea AM, Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel). 2011;3(1):1351-71.
9. Scheffner M, Huibregtse JM, Vierstra RD, and Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993:75, 495-505.
10. Horner SM, DeFilippis RA, Manuelidis L, DiMaio D. Repression of the human papillomavirus E6 gene initiates p53-dependent, telomerase-independent senescence and apoptosis in HeLa cervical carcinoma cells. J Virol. 2004;78:4063-4073.
11. Zhao CY, Szekely L, Bao W, Selivanova G. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation. Cancer Res. 2010;70: 3372-3381.
12. Orlowski RZ, Kuhn DJ. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res. 2008; 14: 1649-1657.
13. Rastogi N, Mishra DP. Therapeutic targeting of cancer cell cycle using proteasome inhibitors. Cell Div. 2012; 7: 26.
14. Bruning A, Vogel M, Mylonas I, Friese K, Burges A. Bortezomib targets the caspase-like proteasome activity in cervical cancer cells, triggering apoptosis that can be enhanced by nelfinavir. Curr Cancer Drug Targets. 2011; 11: 799-80.
15. Anchoori RK, Khan SR, Sueblinvong T, Felthauser A, Iizuka Y, Gavioli R., Destro, F., Isaksson Vogel, R., Peng, S., Roden, R. B. and Bazzaro, M. Stressing the ubiquitinproteasome system without 20S proteolytic inhibition selectively kills cervical cancer cells. PLoS One. 2011; 6:e23888.
16. Bonfili L, Cecarini V, Amici M, Cuccioloni M, Angeletti M, Keller JN, Eleuteri AM. Natural polyphenols as proteasome modulators and their role as anti-cancer compounds. Febs J. 2008; 275: 5512-5526.
17. Yang H, Landis-Piwowar KR, Chen D, Milacic V, Dou QP. Natural compounds with proteasome inhibitory activity for cancer prevention and treatment. Curr Protein Pept Sci. 2008; 9: 227-239.
18. Yang H, Shi G, Dou QP. The tumor proteasome is a primary target for the natural anticancer compound Withaferin A isolated from "Indian winter cherry". MolPharmacol. 2007; 71: 426-437.
19. Yang H, Chen D, Cui QC, Yuan X, Dou QP. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res. 2006; 66:4758-4765.
20. Oyagbemi AA, Saba AB, Azeez OI. Molecular targets of [6]-gingerol: Its potential roles in cancer chemoprevention. Biofactors. 2010; 36: 169-178.
21. Kim EC, Min JK, Kim TY, Lee SJ, Yang HO, Han S, Kim YM, Kwon YG. [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo. BiochemBiophys Res Commun. 2005; 335: 300-308.
22. Lin CB, Lin CC, Tsay GJ. 6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest. Evid Based Complement Alternat Med. 2012;326096.
23. Park YJ, Wen J, Bang S, Park SW, Song SY. [6]-Gingerol induces cell cycle arrest and cell death of mutant p53-expressing pancreatic cancer cells. Yonsei Med J. 2006; 47: 688-697.
24. Chakraborty D, Bishayee K, Ghosh S, Biswas R, Mandal SK, Khuda-Bukhsh AR. [6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: drug-DNA interaction and expression of certain signal genes in HeLa cells. Eur J Pharmacol. 2012; 694: 20-29.
25. Liu Y, Whelan RJ, Pattnaik BR, Ludwig K, Subudhi E, Rowland H, Claussen N, Zucker N, Uppal S, Kushner DM, Felder M, Patankar MS, Kapur A. Terpenoids from Zingiberofficinale (Ginger) induce apoptosis in endometrial cancer cells through the activation of p53. PLoS One. 2012; 7: e53178.
26. Lee SH, Cekanova M, Baek SJ. Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells. MolCarcinog. 2008; 47: 197-208.
27. Rastogi N, Gara RK, Trivedi R, Singh A, Dixit P, Maurya R, Duggal S, Bhatt ML, Singh S, Mishra DP. (6)-Gingerol induced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression. Free RadicBiol Med. 2014; 68:288-301.
28. Munagala R, Kausar H, Munjal C, Gupta RC. Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells. Carcinogenesis. 2011; 32:1697-1705.
29. Lin Z, Bazzaro M, Wang MC, Chan KC, Peng S, Roden RB. Combination of proteasome and HDAC inhibitors for uterine cervical cancer treatment. Clin Cancer Res. 2009; 15: 570-577.
30. Kochetkov DV, Il'inskaia GV, Komarov PG, Strom E, Agapova LS, Ivanov AV, Budanov AV, Frolova EI, Chumakov PM. Transcriptional inhibition of human papilloma virus in cervical carcinoma cells reactivates functions of the tumor suppressor p53. Mol Biol. 2007; 41: 515-523.
31. Saha B, Adhikary A, Ray P, Saha S, Chakraborty S, Mohanty S, Das K, Mukherjee S, Mazumdar M, Lahiri L, Hossain DM, Sa G, Das T. Restoration of tumor suppressor p53 by differentially regulating pro-and anti-p53 networks in HPV-18-infected cervical cancer cells. Oncogene. 2012; 31: 173-186.
32. Blackburn C, Gigstad KM, Hales P, Garcia K, Jones M, Bruzzese FJ, Barrett C, Liu JX, Soucy TA, Sappal DS, Bump N, Olhava EJ, Fleming P, Dick LR, Tsu C, Sintchak MD, Blank JL. Characterization of a new series of noncovalent proteasome inhibitors with exquisite potency and selectivity for the 20S beta5-subunit. Biochem J. 2012; 430: 461-476.
33. Hong YS, Hong SW, Kim SM, Jin DH, Shin JS, Yoon DH, Kim KP, LeeJL, Heo DS, Lee JS, Kim TW. Bortezomib induces G2-M arrest in human colon cancer cells through ROS-inducible phosphorylation of ATM-CHK1. Int J Oncol. 2012; 41: 76-82.
34. Leontieva OV, Blagosklonny MV. Yeastlike chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression. Aging (Albany NY). 2011; 11:107891.
35. Achanta G, Huang P. Role of p53 in sensing oxidative DNA damage in response to reactive oxygen species-generating agents. Cancer Res. 2004; 64: 6233-6239.
36. Lv C, Hong Y, Miao L, Li C, Xu G, Wei S, Wang B, Huang C, Jiao B. Wentilactone A as a novel potential antitumor agent induces apoptosis and G2/M arrest of human lung carcinoma cells, and is mediated by HRas-GTP accumulation to excessively activate the Ras/Raf/ERK/p53-p21 pathway. Cell Death and Disease. 2013; 4: e952.
37. Smits VA, Klompmaker R, Vallenius T, Rijksen G, Makela TP, Medema RH. p21 inhibits Thr161 phosphorylation of Cdc2 to enforce the G2 DNA damage checkpoint. J Biol Chem. 2000; 275: 30638-30643.
38. Gambino V, De Michele G, Venezia O, Migliaccio P, Dall'Olio V, Bernard L, Minardi SP, Della Fazia MA, Bartoli D, Servillo G, Alcalay M, Luzi L, Giorgio M, Scrable H, Pelicci PG, Migliaccio E. Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging. Aging Cell. 2013;12:435-45.
39. Levine AJ, Oren M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 2009;9:749-758.
40. Putral LN, Bywater MJ, Gu W, Saunders NA, Gabrielli BG, Leggatt GR, McMillan NA. RNA interference against human papillomavirus oncogenes in cervical cancer cells results in increased sensitivity to cisplatin. MolPharmacol. 2005; 68:1311-1319.
41. Singh M, Bhui K, Singh R, Shukla Y. Tea polyphenols enhance cisplatinchemosensitivity in cervical cancer cells via induction of apoptosis. Life Sci. 2012; 93:7-16.
42. Cardaci S, Filomeni G, Rotilio G, Ciriolo MR Reactive oxygen species mediate p53 activation and apoptosis induced by sodium nitroprusside in SH-SY5Y cells. MolPharmacol. 2008;74:1234-45.
43. Poveda A, Salazar R, del Campo JM, Mendiola C, Cassinello J, Ojeda B, Arranz JA, Oaknin A, Garcia-Foncillas J, Rubio MJ, Gonzalez Martin A. Update in the management of ovarian and cervical carcinoma. ClinTranslOncol. 2007; 9: 443-451.
44. Lane DP, Cheok CF, Lain S. p53-based cancer therapy. Cold Spring HarbPerspect Biol. 2010;2:a001222.
45. Di Domenico F, Foppoli C, Coccia R, Perluigi M. Antioxidants in cervical cancer: chemopreventive and chemotherapeutic effects of polyphenols. BiochimBiophysActa. 2012;1822:737-47.
46. Asensi M, Ortega A, Mena S, Feddi F, Estrela JM. Natural polyphenols in cancer therapy. Crit Rev Clin Lab Sci. 2011 48:197-216.
47. Minetal Min NY, Kim JH, Choi JH, Liang W, Ko YJ, Rhee S, Bang H, Ham SW, Park AJ, Lee KH.Selective death of cancer cells by preferential induction of reactive oxygen species in response to (-)-epigallocatechin-3-gallate. BiochemBiophys Res Commun.2012; 421: 91-97.
48. Feng R, Ni HM, Wang SY, Tourkova IL, Shurin MR, Harada H, Yin XM. Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. J Biol Chem. 2007; 282: 13468-13476.
49. Wang Q, Zheng XL, Yang L, Shi F, Gao LB, Zhong YJ, Sun H, He F, Lin Y, Wang X.Reactive oxygen speciesmediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells.J ExpClin Cancer Res. 2010 9;29:159.
50. Sharma V, Joseph C, Ghosh S, Agarwal A, Mishra MK, Sen E.Kaempferol induces apoptosis in glioblastoma cells through oxidative stress. Mol Cancer Ther. 2007;6:2544-53.
51. Khan K, Singh A, Mittal M, Sharan K, Singh N, Dixit P, Sanyal S, Maurya R, Chattopadhyay N. [6]-Gingerol induces bone loss in ovary intact adult mice and augments osteoclast function via the transient receptor potential vanilloid 1 channel.MolNutr Food Res. 2012;56:1860-73.
52. Fan JZ, Yang X1, Bi ZG1. The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblastlike MG-63 cells. Braz J Med Biol Res. 2015 28:0. [Epub ahead of print].
53. Zick SM, Djuric Z, Ruffin MT, Litzinger AJ, Normolle DP, Alrawi S, Feng MR, Brenner DE.Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev. 2008;17:1930-6.
54. Reagan-Shaw S, Nihal M, Ahmad N.Dose translation from animal to human studies revisited. FASEB J. 2008;22:659-61.
55. Chen D, Landis-Piwowar KR, Chen MS and Dou PQ. Inhibition of proteasome activity by the dietary flavonoid apigeninis associated with growth inhibitionin cultured breast cancer cells and xenografts. Breast Cancer Res. 2007;9:R80.
56. Chen D, Daniel KG, Chen MS, Kuhn DJ, Landis-Piwowar KR, Dou PQ.Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochemical Pharmacology. 2005. 69:1421-1432.
57. Pandey KB, and Rizv SI, Plant polyphenols as dietary antioxidants in human health and disease Oxidative Medicine and Cellular Longevity. 2009; 2: 270-278.
58. Berghe VW. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes. Pharmacol Res. 2012; 65 :565-76.
59. Surh YJ, Cancer chemoprevention with dietary phytochemicals. Nature Reviews Cancer 3, 768-780.
60. Sanna V, Siddiqui IA, Sechi M, Mukhtar H.Nanoformulation of natural products for prevention and therapy of prostate cancer. Cancer Lett. 2013;28:142-51.
61. Lee WH, Loo CY, Young PM, Traini D, Mason RS, Rohanizadeh R.Recent advances in curcuminnanoformulation for cancer therapy. Expert Opin Drug Deliv. 2014 ;11:1183-201.