Ursolic acid inhibited growth of hepatocellular carcinoma HepG2 cells through AMPKα-mediated reduction of DNA methyltransferase 1

Molecular and Cellular Biochemistry

Volumn 402, Issue 1-2, 2015, Pages 63-74

  Yie, Yinyi ^a   Zhao, Shunyu ^a   Tang, Qin ^a   Zheng, Fang ^a   Wu, Jingjing ^a   Yang, Li Juan ^a   Deng, Shi Guan ^a   Hann, Swei Sunny ^a  

^a GUANGDONG PROVINCIAL HOSPITAL OF CHINESE MEDICINE   (China)

Author keywords

AMPK ; DNMT1; Human hepatocellular carcinoma cells; Sp1; Ursolic acid

Indexed keywords

DNA METHYLTRANSFERASE 1; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ALPHA; METFORMIN; TRANSCRIPTION FACTOR SP1; UNCLASSIFIED DRUG; URSOLIC ACID; ANTINEOPLASTIC AGENT; DNA (CYTOSINE 5) METHYLTRANSFERASE; DNA (CYTOSINE-5-)-METHYLTRANSFERASE 1; SP1 PROTEIN, HUMAN; TRITERPENE;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL GROWTH; CONTROLLED STUDY; DOSE RESPONSE; ENZYME PHOSPHORYLATION; HEPG2 CELL LINE; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; PROTEIN EXPRESSION; CELL PROLIFERATION; DRUG EFFECTS; DRUG SCREENING; GENE EXPRESSION REGULATION; IC50; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN PROCESSING;

AMP-ACTIVATED PROTEIN KINASES; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; CARCINOMA, HEPATOCELLULAR; CELL PROLIFERATION; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DRUG SCREENING ASSAYS, ANTITUMOR; GENE EXPRESSION REGULATION, NEOPLASTIC; HEP G2 CELLS; HUMANS; INHIBITORY CONCENTRATION 50; METFORMIN; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; SP1 TRANSCRIPTION FACTOR; TRITERPENES;

EID: 84925487388     PISSN: 03008177     EISSN: 15734919     Source Type: Journal    
DOI: 10.1007/s11010-014-2314-x     Document Type: Article

References (48)

1. El-S HB (2011) Hepatocellular carcinoma. N Engl J Med 365:1118–1127. doi:10.1056/NEJMra1001683
2. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29. doi:10.3322/caac.21208
3. Bush DA, Kayali Z, Grove R, Slater JD (2011) The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer 117:3053–3059. doi:10.1002/cncr.25809
4. Sun B, Meng J, Xiang T, Chen Z, Li Y, Lu L, Zhang S, Chen X (2013) Jianpijiedu fang improves survival of hepatocarcinoma mice by affecting phosphatase and tensin homolog, phosphoinositide 3-kinase, and focal adhesion kinase. J Tradit Chin Med 33:479–485
5. Hu F, Han J, Zhai B, Ming X, Zhuang L, Liu Y, Pan S, Liu T (2014) Blocking autophagy enhances the apoptosis effect of bufalin on human hepatocellular carcinoma cells through endoplasmic reticulum stress and JNK activation. Apoptosis 19:210–223. doi:10.1007/s10495-013-0914-7
6. Wang S, Wang J, Lin P, Li Z, Yao C, Chang G, Li X (2013) Short-term curative effect of endovascular stent-graft treatment for aortic diseases in China: a systematic review. PLoS One 8:e71012. doi:10.1371/journal.pone.0071012
7. Hu Y, Wang S, Wu X, Zhang J, Chen R, Chen M, Wang Y (2013) Chinese herbal medicine-derived compounds for cancer therapy: a focus on hepatocellular carcinoma. J Ethnopharmacol 149:601–612. doi:10.1016/j.jep.2013.07.030
8. Li X, Zhang J, Gao W, Wang H (2012) Study on chemical composition, anti-inflammatory and anti-microbial activities of extracts from Chinese pear fruit (Pyrus bretschneideri Rehd.). Food Chem Toxicol 50:3673–3679. doi:10.1016/j.fct.2012.07.019
9. Kong L, Li S, Liao Q, Zhang Y, Sun R, Zhu X, Zhang Q, Wang J, Wu X, Fang X, Zhu Y (2013) Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity. Antiviral Res 98:44–53. doi:10.1016/j.antiviral.2013.02.003
10. Zang LL, Wu BN, Lin Y, Wang J, Fu L, Tang ZY (2014) Research progress of ursolic acid’s anti-tumor actions. Chin J Integr Med 20:72–79. doi:10.1007/s11655-013-1541-4
11. Liu W, Tan X, Shu L, Sun H, Song J, Jin P, Yu S, Sun M, Jia X (2012) Ursolic acid inhibits cigarette smoke extract-induced human bronchial epithelial cell injury and prevents development of lung cancer. Molecules 17:9104–9115. doi:10.3390/molecules17089104
12. Tang Q, Ji Q, Tang Y, Chen T, Pan G, Hu S, Bao Y, Peng W, Yin P (2014) Mitochondrial translocation of cofilin-1 promotes apoptosis of gastric cancer BGC-823 cells induced by ursolic acid. Tumour Biol 35:2451–2459. doi:10.1007/s13277-013-1325-7
13. Li J, Liang X, Yang X (2012) Ursolic acid inhibits growth and induces apoptosis in gemcitabine-resistant human pancreatic cancer via the JNK and PI3K/Akt/NF-kappaB pathways. Oncol Rep 28:501–510. doi:10.3892/or.2012.1827
14. Son HS, Kwon HY, Sohn EJ, Lee JH, Woo HJ, Yun M, Kim SH, Kim YC (2013) Activation of AMP-activated protein kinase and phosphorylation of glycogen synthase kinase3 beta mediate ursolic acid induced apoptosis in HepG2 liver cancer cells. Phytother Res 27:1714–1722. doi:10.1002/ptr.4925
15. Wang J, Liu L, Qiu H, Zhang X, Guo W, Chen W, Tian Y, Fu L, Shi D, Cheng J, Huang W, Deng W (2013) Ursolic acid simultaneously targets multiple signaling pathways to suppress proliferation and induce apoptosis in colon cancer cells. PLoS One 8:e63872. doi:10.1371/journal.pone.0063872
16. Scott A, Song J, Ewing R, Wang Z (2014) Regulation of protein stability of DNA methyltransferase 1 by post-translational modifications. Acta Biochim Biophys Sin (Shanghai) 46:199–203. doi:10.1093/abbs/gmt146
17. Mudbhary R, Hoshida Y, Chernyavskaya Y, Jacob V, Villanueva A, Fiel MI, Chen X, Kojima K, Thung S, Bronson RT, Lachenmayer A, Revill K, Alsinet C, Sachidanandam R, Desai A, SenBanerjee S, Ukomadu C, Llovet JM, Sadler KC (2014) UHRF1 overexpression drives DNA hypomethylation and hepatocellular carcinoma. Cancer Cell 25:196–209. doi:10.1016/j.ccr.2014.01.003
18. Azizi M, Teimoori-Toolabi L, Arzanani MK, Azadmanesh K, Fard-Esfahani P, Zeinali S (2014) MicroRNA-148b and microRNA-152 reactivate tumor suppressor genes through suppression of DNA methyltransferase-1 gene in pancreatic cancer cell lines. Cancer Biol Ther 15(4):419–427
19. Gao J, Wang L, Xu J, Zheng J, Man X, Wu H, Jin J, Wang K, Xiao H, Li S, Li Z (2013) Aberrant DNA methyltransferase expression in pancreatic ductal adenocarcinoma development and progression. J Exp Clin Cancer Res 32:86. doi:10.1186/1756-9966-32-86
20. Fan H, Zhao ZJ, Cheng J, Su XW, Wu QX, Shan YF (2009) Overexpression of DNA methyltransferase 1 and its biological significance in primary hepatocellular carcinoma. World J Gastroenterol 15:2020–2026
21. Flis S, Gnyszka A, Flis K (2014) DNA methyltransferase inhibitors improve the effect of chemotherapeutic agents in SW48 and HT-29 colorectal cancer cells. PLoS One 9:e92305. doi:10.1371/journal.pone.0092305
22. Konac E, Varol N, Yilmaz A, Menevse S, Sozen S (2013) DNA methyltransferase inhibitor-mediated apoptosis in the Wnt/beta-catenin signal pathway in a renal cell carcinoma cell line. Exp Biol Med (Maywood) 238:1009–1016. doi:10.1177/1535370213498984
23. Nakamura K, Aizawa K, Nakabayashi K, Kato N, Yamauchi J, Hata K, Tanoue A (2013) DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis. PLoS One 8:e54036. doi:10.1371/journal.pone.0054036
24. Zheng F, Tang Q, Wu J, Zhao S, Liang Z, Li L, Wu W, Hann S (2014) p38alpha MAPK-mediated induction and interaction of FOXO3a and p53 contribute to the inhibited-growth and induced-apoptosis of human lung adenocarcinoma cells by berberine. J Exp Clin Cancer Res 33:36. doi:10.1186/1756-9966-33-36
25. Kambe A, Iguchi G, Moon Y, Kamitani H, Watanabe T, Eling TE (2008) Regulation of EP4 expression via the Sp-1 transcription factor: inhibition of expression by anti-cancer agents. Biochim Biophys Acta 1783:1211–1219. doi:10.1016/j.bbamcr.2008.01.032
26. Hann SS, Tang Q, Zheng F, Zhao S, Chen J, Wang Z (2014) Repression of phosphoinositide-dependent protein kinase 1 expression by ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer cell growth. Mol Cancer 13:149. doi:10.1186/1476-4598-13-149
27. Yu Z, Xiao Q, Zhao L, Ren J, Bai X, Sun M, Wu H, Liu X, Song Z, Yan Y, Mi X, Wang E, Jin F, Wei M (2014) DNA methyltransferase 1/3a overexpression in sporadic breast cancer is associated with reduced expression of estrogen receptor-alpha/breast cancer susceptibility gene 1 and poor prognosis. Mol Carcinog. doi:10.1002/mc.22133
28. Liu WB, Cui ZH, Ao L, Zhou ZY, Zhou YH, Yuan XY, Xiang YL, Liu JY, Cao J (2011) Aberrant methylation accounts for cell adhesion-related gene silencing during 3-methylcholanthrene and diethylnitrosamine induced multistep rat lung carcinogenesis associated with overexpression of DNA methyltransferases 1 and 3a. Toxicol Appl Pharmacol 251:70–78. doi:10.1016/j.taap.2010.12.002
29. Lin RK, Wu CY, Chang JW, Juan LJ, Hsu HS, Chen CY, Lu YY, Tang YA, Yang YC, Yang PC, Wang YC (2010) Dysregulation of p53/Sp1 control leads to DNA methyltransferase-1 overexpression in lung cancer. Cancer Res 70:5807–5817. doi:10.1158/0008-5472.CAN-09-4161
30. Huang SK, Scruggs AM, Donaghy J, McEachin RC, Fisher AS, Richardson BC, Peters-Golden M (2012) Prostaglandin E(2) increases fibroblast gene-specific and global DNA methylation via increased DNA methyltransferase expression. FASEB J 26:3703–3714. doi:10.1096/fj.11-203323
31. Li X, Shen Q, Zhang D, Mei X, Ran W, Xu Y, Yu G (2013) Functional groups determine biochar properties (pH and EC) as studied by two-dimensional C NMR correlation spectroscopy. PLoS One 8:e65949. doi:10.1371/journal.pone.0065949
32. Hoenerhoff MJ, Pandiri AR, Snyder SA, Hong HH, Ton TV, Peddada S, Shockley K, Witt K, Chan P, Rider C, Kooistra L, Nyska A, Sills RC (2013) Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways. Toxicol Pathol 41:826–841. doi:10.1177/0192623312467520
33. Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar A, Diagaradjane P, Wei C, Baladandayuthapani V, Krishnan S, Guha S, Aggarwal BB (2012) Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res 18:4942–4953. doi:10.1158/1078-0432.ccr-11-2805
34. Yu YX, Gu ZL, Yin JL, Chou WH, Kwok CY, Qin ZH, Liang ZQ (2010) Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway. Chin Med J (Engl) 123:1915–1923
35. Liang J, Mills GB (2013) AMPK: a contextual oncogene or tumor suppressor? Cancer Res 73:2929–2935. doi:10.1158/0008-5472.CAN-12-3876
36. He Y, Li Y, Zhao T, Wang Y, Sun C (2013) Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway. PLoS One 8:e70135. doi:10.1371/journal.pone.0070135
37. Zheng QY, Jin FS, Yao C, Zhang T, Zhang GH, Ai X (2012) Ursolic acid-induced AMP-activated protein kinase (AMPK) activation contributes to growth inhibition and apoptosis in human bladder cancer T24 cells. Biochem Biophys Res Commun 419:741–747. doi:10.1016/j.bbrc.2012.02.093
38. Liu X, Goldstein AS (2014) Inflammation promotes prostate differentiation. Proc Natl Acad Sci USA 111:1666–1667. doi:10.1073/pnas.1323181111
39. Sontag RL, Weber TJ (2012) Ectopic ERK expression induces phenotypic conversion of C10 cells and alters DNA methyltransferase expression. BMC Res Notes 5:217. doi:10.1186/1756-0500-5-217
40. Kassis ES, Zhao M, Hong JA, Chen GA, Nguyen DM, Schrump DS (2006) Depletion of DNA methyltransferase 1 and/or DNA methyltransferase 3b mediates growth arrest and apoptosis in lung and esophageal cancer and malignant pleural mesothelioma cells. J Thorac Cardiovasc Surg 131:298–306. doi:10.1016/j.jtcvs.2005.05.022
41. Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Hikiba Y, Obi S, Goto T, Kang YJ, Maeda S, Yoshida H, Omata M, Asahara H, Koike K (2013) MicroRNA-140 acts as a liver tumor suppressor by controlling NF-kappaB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression. Hepatology 57:162–170. doi:10.1002/hep.26011
42. Brodie SA, Li G, El-Kommos A, Kang H, Ramalingam SS, Behera M, Gandhi K, Kowalski J, Sica GL, Khuri FR, Vertino PM, Brandes JC (2014) Class I HDACs are mediators of smoke carcinogen-induced stabilization of DNMT1 and serve as promising targets for chemoprevention of lung cancer. Cancer Prev Res (Phila) 7:351–361. doi:10.1158/1940-6207.CAPR-13-0254
43. Wang W, Cheng X, Lu J, Wei J, Fu G, Zhu F, Jia C, Zhou L, Xie H, Zheng S (2010) Mitofusin-2 is a novel direct target of p53. Biochem Biophys Res Commun 400:587–592. doi:10.1016/j.bbrc.2010.08.108
44. Huang J, Wang Y, Guo Y, Sun S (2010) Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology 52:60–70. doi:10.1002/hep.23660
45. Saito Y, Kanai Y, Nakagawa T, Sakamoto M, Saito H, Ishii H, Hirohashi S (2003) Increased protein expression of DNA methyltransferase (DNMT) 1 is significantly correlated with the malignant potential and poor prognosis of human hepatocellular carcinomas. Int J Cancer 105:527–532. doi:10.1002/ijc.11127
46. Karpe PA, Tikoo K (2014) Heat shock prevents insulin resistance-induced vascular complications by augmenting angiotensin-(1-7) signaling. Diabetes 63:1124–1139. doi:10.2337/db13-1267
47. Chai G, Li L, Zhou W, Wu L, Zhao Y, Wang D, Lu S, Yu Y, Wang H, McNutt MA, Hu YG, Chen Y, Yang Y, Wu X, Otterson GA, Zhu WG (2008) HDAC inhibitors act with 5-aza-2′-deoxycytidine to inhibit cell proliferation by suppressing removal of incorporated abases in lung cancer cells. PLoS One 3:e2445. doi:10.1371/journal.pone.0002445
48. Li J, Zou WX, Chang KS (2014) Inhibition of Sp1 functions by its sequestration into PML nuclear bodies. PLoS One 9:e94450. doi:10.1371/journal.pone.0094450