Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition

Oncotarget

Volumn 6, Issue 23, 2015, Pages 19580-19591

  Khan, Md Asaduzzaman ^a   Tania, Mousumi ^a   Wei, Chunli ^a   Mei, Zhiqiang ^a   Fu, Shelly ^a,b   Cheng, Jingliang ^a   Xu, Jianming ^a,c   Fu, Junjiang ^a  

^a Sichuan Medical University   (China)

^b Michael E DeBakey High School for Health Professions   (United States)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Cancer metastasis; DNA methylation; Epithelial to mesenchymal transition; Thymoquinone; TWIST1

Indexed keywords

DOXYCYCLINE; NERVE CELL ADHESION MOLECULE; THYMOQUINONE; UVOMORULIN; ANTINEOPLASTIC AGENT; BENZOQUINONE DERIVATIVE; MESSENGER RNA; NUCLEAR PROTEIN; TWIST RELATED PROTEIN 1; TWIST1 PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BREAST METASTASIS; CANCER CELL LINE; CANCER INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA METHYLATION; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; GENE; GENE ACTIVITY; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; GENE TARGETING; HELA CELL LINE; HUMAN; HUMAN CELL; LUNG METASTASIS; METASTASIS; METASTASIS INHIBITION; MITOSIS INHIBITION; MOUSE; NONHUMAN; PROMOTER REGION; TWIST1 GENE; UPREGULATION; UTERINE CERVIX CANCER; ANIMAL; BAGG ALBINO MOUSE; BREAST NEOPLASMS; CELL MOTION; DOSE RESPONSE; DRUG EFFECTS; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; LUNG NEOPLASMS; METABOLISM; PATHOLOGY; RNA INTERFERENCE; SECONDARY; SIGNAL TRANSDUCTION; TIME FACTOR; TUMOR INVASION;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BENZOQUINONES; BREAST NEOPLASMS; CELL MOVEMENT; DNA METHYLATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HEK293 CELLS; HELA CELLS; HUMANS; LUNG NEOPLASMS; MICE, INBRED BALB C; NEOPLASM INVASIVENESS; NUCLEAR PROTEINS; PROMOTER REGIONS, GENETIC; RNA INTERFERENCE; RNA, MESSENGER; SIGNAL TRANSDUCTION; TIME FACTORS; TRANSCRIPTION, GENETIC; TRANSFECTION; TWIST-RELATED PROTEIN 1;

EID: 84939220366     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.3973     Document Type: Article

References (48)

1. Chiang AC, Massagué J. Molecular basis of metastasis. N Engl J Med. 2008; 359:2814-2823.
2. Robins SL, Cotran RS. Neoplasia. In: Pathologic basis of disease. Editors: Kumar V, Abbas AK, Fausto N (7th edition). India: Thomson Press, 2009: 292-306.
3. Kang Y, Massagué J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 2004; 118:277-279.
4. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004; 117:927-939.
5. Khan MA, Chen HC, Zhang D, Fu J. Twist: a molecular target in cancer therapeutics. Tumour Biol. 2013; 34:2497-2506.
6. Tania M, Khan MA, Fu J. Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer. Tumour Biol. 2014; 35:7335-7342.
7. Mehrotra J, Vali M, McVeigh M, Kominsky SL, Fackler MJ, Lahti-Domenici J, Polyak K, Sacchi N, Garrett-Mayer E, Argani P, Sukumar S. Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung. Clin Cancer Res. 2004; 10:3104-3109.
8. Salih B, Sipahi T, Oybak Dönmez E. Ancient nigella seeds from Boyali Höyük in north-central Turkey. J Ethnopharmacol. 2009; 124:416-420.
9. Khan MA, Chen HC, Tania M, Zhang DZ. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med. 2011; 8:226-232.
10. Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F, Kishore K. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013; 3:337-352.
11. Yi T, Cho SG, Yi Z, Pang X, Rodriguez M, Wang Y, Sethi G, Aggarwal BB, Liu M. Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol Cancer Ther. 2008; 7:1789-1796.
12. Torres MP, Ponnusamy MP, Chakraborty S, Smith LM, Das S, Arafat HA, Batra SK. Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Mol Cancer Ther. 2010; 9:1419-1431.
13. Ahmad I, Muneer KM, Tamimi IA, Chang ME, Ata MO, Yusuf N. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. Toxicol Appl Pharmacol. 2013; 270:70-76.
14. Pinho AV, Rooman I, Real FX. p53-dependent regulation of growth, epithelial-mesenchymal transition and stemness in normal pancreatic epithelial cells. Cell Cycle. 2011; 10:1312-1321.
15. Fu J, Qin L, He T, Qin J, Hong J, Wong J, Liao L, Xu J. The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis. Cell Res. 2011; 21:275-289.
16. Hong J, Zhou J, Fu J, He T, Qin J, Wang L, Liao L, Xu J. Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. Cancer Res. 2011; 71:3980-3990.
17. Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad. 2008; 20:25-27.
18. Woo CC, Hsu A, Kumar AP, Sethi G, Tan KH. Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: the role of p3 MAPK and ROS. PLoS One. 2013; 8:e75356.
19. Banerjee S, Azmi AS, Padhye S, Singh MW, Baruah JB, Philip PA, Sarkar FH, Mohammad RM. Structure-activity studies on therapeutic potential of Thymoquinone analogs in pancreatic cancer. Pharm Res. 2010; 27:1146-1158.
20. Acharya BR, Chatterjee A, Ganguli A, Bhattacharya S, Chakrabarti G. Thymoquinone inhibits microtubule polymerization by tubulin binding and causes mitotic arrest following apoptosis in A549 cells. Biochimie. 2014; 97:78-91.
21. Sutton KM, Greenshields AL, Hoskin DW. Thymoquinone, a bioactive component of black caraway seeds, causes G1 phase cell cycle arrest and apoptosis in triple-negative breast cancer cells with mutant p53. Nutr Cancer. 2014; 66:408-418.
22. Ashour AE, Abd-Allah AR, Korashy HM, Attia SM, Alzahrani AZ, Saquib Q, Bakheet SA, Abdel-Hamied HE, Jamal S, Rishi AK. Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis. Mol Cell Biochem. 2014; 389:85-98.
23. Chu SC, Hsieh YS, Yu CC, Lai YY, Chen PN. Thymoquinone Induces Cell Death in Human Squamous Carcinoma Cells via Caspase Activation-Dependent Apoptosis and LC3-II Activation-Dependent Autophagy. PLoS One. 2014; 9:e101579.
24. Kundu J, Choi BY, Jeong CH, Kundu JK, Chun KS. Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src mediated phosphorylation of EGF receptor tyrosine kinase. Oncol Rep. 2014; 32:821-828.
25. Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Höfler H, Becker KF. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol. 2002; 161:1881-1891.
26. Niu RF, Zhang L, Xi GM, Wei XY, Yang Y, Shi YR, Hao XS. Up-regulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2007; 26:385-394.
27. Huang RY, Wong MK, Tan TZ, Kuay KT, Ng AH, Chung VY, Chu YS, Matsumura N, Lai HC, Lee YF, Sim WJ, Chai C, Pietschmann E, et al. An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530). Cell Death Dis. 2013; 4:e915.
28. Yu Q, Zhang K, Wang X, Liu X, Zhang Z. Expression of transcription factors snail, slug, and twist in human bladder carcinoma. J Exp Clin Cancer Res. 2010; 29:119.
29. Vesuna F, Lisok A, Kimble B, Domek J, Kato Y, van der Groep P, Artemov D, Kowalski J, Carraway H, van Diest P, Raman V. Twist contributes to hormone resistance in breast cancer by downregulating estrogen receptor-a. Oncogene. 2012; 31:3223-3234.
30. Yamada S, Okumura N, Wei L, Fuchs BC, Fujii T, Sugimoto H, Nomoto S, Takeda S, Tanabe KK, Kodera Y. Epithelial to Mesenchymal Transition is Associated with Shorter Disease-Free Survival in Hepatocellular Carcinoma. Ann Surg Oncol. 2014; 21:3882-3890.
31. Zhang L, Yang M, Gan L, He T, Xiao X, Stewart MD, Liu X, Yang L, Zhang T, Zhao Y, Fu J. DLX4 upregulates TWIST and enhances tumor migration, invasion and metastasis. Int J Biol Sci. 2012; 8:1178-1187.
32. Fu J, Zhang L, He T, Xiao X, Liu X, Wang L, Yang L, Yang M, Zhang T, Chen R, Xu J. TWIST represses estrogen receptor-alpha expression by recruiting the NuRD protein complex in breast cancer cells. Int J Biol Sci. 2012; 8:522-532.
33. Sawada K, Mitra AK, Radjabi AR, Bhaskar V, Kistner EO, Tretiakova M, Jagadeeswaran S, Montag A, Becker A, Kenny HA, Peter ME, Ramakrishnan V, Yamada SD, et al. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res. 2008; 68:2329-2339.
34. Lee KW, Lee NK, Ham S, Roh TY, Kim SH. Twist1 is essential in maintaining mesenchymal state and tumor-initiating properties in synovial sarcoma. Cancer Lett. 2014; 343:62-73.
35. Lang M, Borgmann M, Oberhuber G, Evstatiev R, Jimenez K, Dammann KW, Jambrich M, Khare V, Campregher C, Ristl R, Gasche C. Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling. Mol Cancer. 2013; 12:41.
36. Howe LR, Watanabe O, Leonard J, Brown AM. Twist is up-regulated in response to Wnt1 and inhibits mouse mammary cell differentiation. Cancer Res. 2003; 63:1906-1913.
37. Vichalkovski A, Gresko E, Hess D, Restuccia DF, Hemmings BA. PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage. Oncogene. 2010; 29:3554-3565.
38. Rajput S, Kumar BN, Sarkar S, Das S, Azab B, Santhekadur PK, Das SK, Emdad L, Sarkar D, Fisher PB, Mandal M. Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer. PLoS One. 2013; 8:e61342.
39. Gort EH, Suijkerbuijk KP, Roothaan SM, Raman V, Vooijs M, van der Wall E, van Diest PJ. Methylation of the TWIST1 promoter, TWIST1 mRNA levels, and immunohistochemical expression of TWIST1 in breast cancer. Cancer. Epidemiol Biomarkers Prev. 2008; 17:3325-3330.
40. Galván JA, Helbling M, Koelzer VH, Tschan MP, Berger MD, Hädrich M, Schnüriger B, Karamitopoulou E, Dawson H, Inderbitzin D, Lugli A, Zlobec I. TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer. Oncotarget. 2015; 6:874-885.
41. Huang KT, Dobrovic A, Yan M, Karim RZ, Lee CS, Lakhani SR, Fox SB. DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast. Breast Cancer Res Treat. 2010; 124:555-565.
42. Robert MF, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A, MacLeod AR. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet. 2003; 33:61-65.
43. Chen BF, Chan WY. The de novo DNA methyltransferase DNMT3A in development and cancer. Epigenetics. 2014; 9:669-677.
44. Ali A, Wang Z, Fu J, Ji L, Liu J, Li L, Wang H, Chen J, Caulin C, Myers JN, Zhang P, Xiao J, Zhang B, Li X. Differential regulation of the REGγ-proteasome pathway by p53/TGF-ß signalling and mutant p53 in cancer cells. Nat Commun. 2013; 4:2667.
45. Li L, Dang Y, Zhang J, Yan W, Zhai W, Chen H, Li K, Tong L, Gao X, Amjad A, Ji L, Jing T, Jiang Z, Shi K, Yao L, Song D, Liu T, Yang X, Yang C, Cai X, Xu W, Huang Q, He J, Liu J, Chen T, Moses RE, Fu J, Xiao J, Li X. REGγ is critical for skin carcinogenesis by modulating the Wnt/ß-catenin pathway. Nat Commun. 2015; 6:6875.
46. Fu J, Yoon HG, Qin J, Wong J. Regulation of P-TEFb elongation complex activity by CDK9 acetylation. Mol Cell Biol. 2007; 27:4641-4651.
47. Wiederschain D, Wee S, Chen L, Loo A, Yang G, Huang A, Chen Y, Caponigro G, Yao YM, Lengauer C, Sellers WR, Benson JD. Single-vector inducible lentiviral RNAi system for oncology target validation. Cell Cycle. 2009; 8:498-504.
48. Qin L, Liu Z, Chen H, Xu J. The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis. Cancer Res. 2009; 69:3819-3827.