Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells

Oncotarget

Volumn 6, Issue 30, 2015, Pages 28851-28866

  Tsai, Jen Pi ^a,b   Lee, Chien Hsing ^c,d   Ying, Tsung Ho ^e   Lin, Chu Liang ^e   Lin, Chia Liang ^e   Hsueh, Jung Tsung ^e   Hsieh, Yi Hsien ^e,f  

^a BUDDHIST TZU CHI GENERAL HOSPITAL   (Taiwan)

^b TZU CHI UNIVERSITY   (Taiwan)

^c CHANG JUNG CHRISTIAN UNIVERSITY   (Taiwan)

^d CHINA MEDICAL UNIVERSITY CHILDREN S HOSPITAL   (Taiwan)

^e CHUNG SHAN MEDICAL UNIVERSITY   (Taiwan)

^f CHUNG SHAN MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

Author keywords

Apoptosis; Autophagy; Cervical cancer; Licochalcone A

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 3 (4,5 DIMETHYL 2 THIAZOLYL) 2,5 DIPHENYLTETRAZOLIUM BROMIDE; 3 METHYLADENINE; AUTOPHAGY PROTEIN 12; AUTOPHAGY PROTEIN 5; AUTOPHAGY PROTEIN 7; BAFILOMYCIN A1; CARRIER PROTEINS AND BINDING PROTEINS; LICOCHALCONE A; MAMMALIAN TARGET OF RAPAMYCIN; MICROTUBULE ASSOCIATED PROTEIN 1 LIGHT CHAIN 3 PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN KINASE B; UNCLASSIFIED DRUG; 3-METHYLADENINE; ADENINE; ANTINEOPLASTIC AGENT; CHALCONE DERIVATIVE; MACROLIDE; MTOR PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; AUTOPHAGY; CANCER CELL DESTRUCTION; CANCER CELL LINE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG MECHANISM; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MITOCHONDRION; MOUSE; NONHUMAN; PROTEIN EXPRESSION; UTERINE CERVIX CANCER; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; BAGG ALBINO MOUSE; CELL PROLIFERATION; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; ENZYMOLOGY; GENETIC TRANSFECTION; GENETICS; HELA CELL LINE; METABOLISM; NUDE MOUSE; PATHOLOGY; PHOSPHORYLATION; SIGNAL TRANSDUCTION; TIME FACTOR; TUMOR VOLUME; UTERINE CERVICAL NEOPLASMS;

ADENINE; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; AUTOPHAGY; CELL PROLIFERATION; CHALCONES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HELA CELLS; HUMANS; MACROLIDES; MICE; MICE, INBRED BALB C; MICE, NUDE; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; TIME FACTORS; TOR SERINE-THREONINE KINASES; TRANSFECTION; TUMOR BURDEN; UTERINE CERVICAL NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84945121867     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.4767     Document Type: Article

References (68)

1. Waggoner SE. Cervical cancer. Lancet. 2003; 361:2217-2225.
2. Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain JM, Garcia FA, Moriarty AT, Waxman AG, Wilbur DC, Wentzensen N, Downs LS Jr, Spitzer M, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. J Low Genit Tract Dis. 2012; 16:175-204.
3. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer. a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008; 26:5802-5812.
4. Kontos CK, Christodoulou MI, Scorilas A. Apoptosis-related BCL2-family members: Key players in chemotherapy. Anticancer Agents Med Chem. 2014; 14:353-374.
5. Janku F, McConkey DJ, Hong DS, Kurzrock R. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011; 8:528-539.
6. Criollo A, Maiuri MC, Tasdemir E, Vitale I, Fiebig AA, Andrews D, Molgó J, Díaz J, Lavandero S, Harper F, Pierron G, di Stefano D, Rizzuto R, et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 2007; 14:1029-1039.
7. Akar U, Ozpolat B, Mehta K, Fok J, Kondo Y, LopezBerestein G. Tissue transglutaminase inhibits autophagy in pancreatic cancer cells. Mol Cancer Res. 2007; 5:241-249.
8. Mizushima N, Yoshimori T, Ohsumi Y. The role of ATG proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011; 27:107-132.
9. Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh BH, Jung JU. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol. 2006; 8:688-699.
10. Webber JL. Regulation of autophagy by p38alpha MAPK. Autophagy. 2010; 6:292-293.
11. Sun H, Wang Z, Yakisich JS. Natural products targeting autophagy via the PI3K/Akt/mTOR pathway as anticancer agents. Anticancer Agents Med Chem. 2013; 13:1048-1056.
12. Salazar M, Carracedo A, Salanueva IJ, HernándezTiedra S, Lorente M, Egia A, Vázquez P, Blázquez C, Torres S, García S, Nowak J, Fimia GM, Piacentini M, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009; 119:1359-1372.
13. Aoki H, Takada Y, Kondo S, Sawaya R, Aggarwal BB, Kondo Y. Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol Pharmacol. 2007; 72:29-39.
14. Bruning A. Inhibition of mTOR signaling by quercetin in cancer treatment and prevention. Anticancer Agents Med Chem. 2013; 13:1025-1031.
15. Baehrecke EH. Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol. 2005; 6:505-510.
16. Scott RC, Juhasz G, Neufeld TP. Direct induction of autophagy by ATG1 inhibits cell growth and induces apoptotic cell death. Curr Biol. 2007; 17:1-11.
17. Kwon HS, Park JH, Kim DH, Kim YH, Park JH, Shin HK, Kim JK. Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice. J Mol Med (Berl). 2008; 86:1287-1295.
18. Chu X, Ci X, Wei M, Yang X, Cao Q, Guan M, Li H, Deng Y, Feng H, Deng X. Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo. J Agric Food Chem. 2012; 60:3947-3954.
19. Rafi MM, Rosen RT, Vassil A, Ho CT, Zhang H, Ghai G, Lambert G, DiPaola RS. Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res. 2000; 20:2653-2658.
20. Kim JK, Shin EK, Park JH, Kim YH, Park JH. Antitumor and antimetastatic effects of licochalcone A in mouse models. J Mol Med (Berl). 2010; 88:829-838.
21. Park JH, Lim HJ, Lee KS, Lee S, Kwak HJ, Cha JH, Park HY. Anti-proliferative effect of licochalcone A on vascular smooth muscle cells. Biol Pharm Bull. 2008; 31:1996-2000.
22. Tsai JP, Hsiao PC, Yang SF, Hsieh SC, Bau DT, Ling CL, Pai CL, Hsieh YH. Licochalcone A suppresses migration and invasion of human hepatocellular carcinoma cells through downregulation of MKK4/JNK via NF-kappaB mediated urokinase plasminogen activator expression. PLoS One. 2014; 9:e86537.
23. Zhang X, Chen LX, Ouyang L, Cheng Y, Liu B. Plant natural compounds: targeting pathways of autophagy as anticancer therapeutic agents. Cell Prolif. 2012; 45:466-476.
24. Yo YT, Shieh GS, Hsu KF, Wu CL, Shiau AL. Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway. J Agric Food Chem. 2009; 57:8266-8273.
25. Beljanski V, Knaak C, Smith CD. A novel sphingosine kinase inhibitor induces autophagy in tumor cells. J Pharmacol Exp Ther. 2010; 333:454-464.
26. Hundeshagen P, Hamacher-Brady A, Eils R, Brady NR. Concurrent detection of autolysosome formation and lysosomal degradation by flow cytometry in a high-content screen for inducers of autophagy. BMC Biol. 2011; 9:38.
27. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000; 19:5720-5728.
28. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004; 36:2503-2518.
29. Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct. 1998; 23:33-42.
30. Qin L, Wang Z, Tao L, Wang Y. ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy. 2010; 6:239-247.
31. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007; 12:9-22.
32. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006; 24:2137-2150.
33. Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU Proof of Principle Study Investigators. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002; 347:1645-1651.
34. Kralova V, Benešová S, Cervinka M, Rudolf E. Seleniteinduced apoptosis and autophagy in colon cancer cells. Toxicol In Vitro. 2012; 26:258-268.
35. Jackson MW, Rusthoven CG, Fisher CM, Schefter TE. Clinical potential of bevacizumab in the treatment of metastatic and locally advanced cervical cancer: current evidence. Onco Targets Ther. 2014; 7:751-759.
36. Fu Y, Hsieh TC, Guo J, Kunicki J, Lee MY, Darzynkiewicz Z, Wu JM. Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells. Biochem Biophys Res Commun. 2004; 322:263-270.
37. Xiao XY, Hao M, Yang XY, Ba Q, Li M, Ni SJ, Wang LS, Du X. Licochalcone A inhibits growth of gastric cancer cells by arresting cell cycle progression and inducing apoptosis. Cancer Lett. 2011; 302:69-75.
38. Hsu YL, Chia CC, Chen PJ, Huang SE, Huang SC, Kuo PL. Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells. Mol Nutr Food Res. 2009; 53:826-835.
39. Hirchaud F, Hermetet F, Ablise M, Fauconnet S, Vuitton DA, Prétet JL, Mougin C. Isoliquiritigenin induces caspase-dependent apoptosis via downregulation of HPV16 E6 expression in cervical cancer Ca Ski cells. Planta Med. 2013; 79:1628-1635.
40. Hsu KF, Wu CL, Huang SC, Wu CM, Hsiao JR, Yo YT, Chen YH, Shiau AL, Chou CY. Cathepsin L mediates resveratrol-induced autophagy and apoptotic cell death in cervical cancer cells. Autophagy. 2009; 5:451-460.
41. Xu Y, Yu H, Qin H, Kang J, Yu C, Zhong J, Su J, Li H, Sun L. Inhibition of autophagy enhances cisplatin cytotoxicity through endoplasmic reticulum stress in human cervical cancer cells. Cancer Lett. 2012; 314:232-243.
42. Chi EY, Viriyapak B, Kwack HS, Lee YK, Kim SI, Lee KH, Park TC. Regulation of paclitaxel-induced programmed cell death by autophagic induction: A model for cervical cancer. Obstet Gynecol Sci. 2013; 56:84-92.
43. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007; 8:741-752.
44. Sun Y, Liu JH, Jin L, Lin SM, Yang Y, Sui YX, Shi H. Over-expression of the Beclin1 gene upregulates chemosensitivity to anti-cancer drugs by enhancing therapy-induced apoptosis in cervix squamous carcinoma CaSki cells. Cancer Lett. 2010; 294:204-210.
45. Hou LL, Gao C, Chen L, Hu GQ, Xie SQ. Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells. Acta Pharmacol Sin. 2013; 34:1403-1410.
46. Eisenberg-Lerner A, Bialik S, Simon HU, Kimchi A. Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 2009; 16:966-975.
47. Sun WL, Chen J, Wang YP, Zheng H. Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development. Autophagy. 2011; 7:1035-1044.
48. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000; 19:5720-5728.
49. Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU. Calpain-mediated cleavage of ATG5 switches autophagy to apoptosis. Nat Cell Biol. 2006; 8:1124-1132.
50. An CH, Kim MS, Yoo NJ, Park SW, Lee SH. Mutational and expressional analyses of ATG5, an autophagy-related gene in gastrointestinal cancers. Pathol Res Pract. 2011; 207:433-437.
51. Li BX, Li CY, Peng RQ, Wu XJ, Wang HY, Wan DS, Zhu XF, Zhang XS. The expression of beclin 1 is associated with favorable prognosis in stage IIIB colon cancers. Autophagy. 2009; 5:303-306.
52. Ahn CH, Jeong EG, Lee JW, Kim MS, Kim SH, Kim SS, Yoo NJ, Lee SH. Expression of beclin-1, an autophagyrelated protein, in gastric and colorectal cancers. APMIS. 2007; 115:1344-1349.
53. Lee JW, Kim KS, An HK, Kim CH, Moon HI, Lee YC. Dendropanoxide induces autophagy through ERK1/2 activation in MG-63 human osteosarcoma cells and autophagy inhibition enhances dendropanoxide-induced apoptosis. PLoS One. 2013; 8:e83611.
54. Zeng Y, Yang X, Wang J, Fan J, Kong Q, Yu X. Aristolochic acid I induced autophagy extenuates cell apoptosis via ERK 1/2 pathway in renal tubular epithelial cells. PLoS One. 2012; 7:e30312.
55. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005; 122:927-939.
56. McCarthy A, Marzec J, Clear A, Petty RD, Coutinho R, Matthews J, Wilson A, Iqbal S, Calaminici M, Gribben JG, Jia L. Dysregulation of autophagy in human follicular lymphoma is independent of overexpression of BCL-2. Oncotarget. 2014; 5:11653-11668.
57. Saeki K, Yuo A, Okuma E, Yazaki Y, Susin SA, Kroemer G, Takaku F. Bcl-2 down-regulation causes autophagy in a caspase-independent manner in human leukemic HL60 cells. Cell Death Differ. 2000; 7:1263-1269.
58. Shimizu S, Eguchi Y, Kamiike W, Waguri S, Uchiyama Y, Matsuda H, Tsujimoto Y. Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of death induced by respiratory chain inhibitors. Oncogene. 1996; 13:21-29.
59. Jiang K, Wang W, Jin X, Wang Z, Ji Z, Meng G. Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells. Oncol Rep. 2015; 33:2711-2718.
60. Singh BN, Kumar D, Shankar S, Srivastava RK. Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. Biochem Pharmacol. 2012; 84:1154-1163.
61. Zhang L, Wang H, Cong Z, Xu J, Zhu J, Ji X, Ding K. Wogonoside induces autophagy-related apoptosis in human glioblastoma cells. Oncol Rep. 2014; 32:1179-1187.
62. Aki T, Yamaguchi K, Fujimiya T, Mizukami Y. Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2. Oncogene. 2003; 22:8529-8535.
63. Hamanaka Y, Mukai M, Shimamura M, Kitagawa T, Nishida T, Isohashi F, Ito T, Nishizawa Y, Tatsuta M, Matsuda H, Inoue M. Suppression of PI3K/mTOR pathway rescues LLC cells from cell death induced by hypoxia. Biochem Biophys Res Commun. 2005; 330:318-326.
64. Hao W, Yuan X, Yu L, Gao C, Sun X, Wang D, Zheng Q. Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways. Sci Rep. 2015; 5:10336.
65. Wu YT, Tan HL, Huang Q, Ong CN, Shen HM. Activation of the PI3K-Akt-mTOR signaling pathway promotes necrotic cell death via suppression of autophagy. Autophagy. 2009; 5:824-834.
66. Zhang DM, Liu JS, Deng LJ, Chen MF, Yiu A, Cao HH, Tian HY, Fung KP, Kurihara H, Pan JX, Ye WC. Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Carcinogenesis. 2013; 34:1331-1342.
67. Degtyarev M, De Mazière A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, Davis DP, Stern HM, Murray LJ, et al. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol. 2008; 183:101-116.
68. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005; 4:988-1004.