Baicalein triggers autophagy and inhibits the protein kinase B/mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells

Phytotherapy Research

Volumn 29, Issue 5, 2015, Pages 674-679

  Wang, Ya Fang ^a   Li, Ting ^a   Tang, Zheng Hai ^a   Chang, Lin Lin ^b   Zhu, Hong ^b   Chen, Xiu Ping ^a   Wang, Yi Tao ^a   Lu, Jin Jian ^a  

^a University of Macau   (Macao)

^b ZHEJIANG UNIVERSITY   (China)

Author keywords

AKT; autophagy; baicalein; hepatocellular carcinoma; ULK1

Indexed keywords

BAICALEIN; CHLOROQUINE; INITIATION FACTOR 4E BINDING PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN; MEMBRANE PROTEIN; MICROTUBULE ASSOCIATED PROTEIN 1A 1B LIGHT CHAIN 3; PROTEIN KINASE B; UNCLASSIFIED DRUG; FLAVANONE DERIVATIVE; MAP1A PROTEIN, HUMAN; MAP1B PROTEIN, HUMAN; MICROTUBULE ASSOCIATED PROTEIN; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CELL VIABILITY; COLONY FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; HEPATOCELLULAR CARCINOMA CELL LINE; LIVER CELL CARCINOMA; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; UPREGULATION; DRUG EFFECTS; HEPG2 CELL LINE; HUMAN; LIVER TUMOR; METABOLISM; PATHOLOGY;

MAMMALIA; SCUTELLARIA RADIX;

AUTOPHAGY; CARCINOMA, HEPATOCELLULAR; FLAVANONES; HEP G2 CELLS; HUMANS; LIVER NEOPLASMS; MICROTUBULE-ASSOCIATED PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84929455114     PISSN: 0951418X     EISSN: 10991573     Source Type: Journal    
DOI: 10.1002/ptr.5298     Document Type: Article

References (36)

1. Cao Y, Dai B, Wang Y, et al,. 2008. In vitro activity of baicalein against Candida albicans biofilms. Int J Antimicrob Agents 32: 73-77.
2. Chen L, Dou J, Su Z, et al,. 2011. Synergistic activity of baicalein with ribavirin against influenza A (H1N1) virus infections in cell culture and in mice. Antiviral Res 91: 314-320.
3. Chen K, Zhang S, Ji Y, et al,. 2013. Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway. PLoS One 8: e72927.
4. Cheng YH, Li LA, Lin P, et al,. 2012. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation. Toxicol Appl Pharmacol 263: 360-367.
5. Cui Q, Tashiro S, Onodera S, Minami M, Ikejima T,. 2007. Autophagy preceded apoptosis in oridonin-treated human breast cancer MCF-7 cells. Biol Pharm Bull 30: 859-864.
6. Ding Q, Bao JL, Zhao WW, Hu YY, Lu JJ, Chen XP,. 2014. Natural autophagy regulators in cancer therapy: a review. Phytochemistry Rev. DOI 10.1007/s11101-11014-19339-11103
7. Egan DF, Shackelford DB, Mihaylova MM, et al,. 2011. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331: 456-461.
8. Fan GW, Zhang Y, Jiang X, et al,. 2013. Anti-inflammatory activity of baicalein in LPS-stimulated RAW264.7 macrophages via estrogen receptor and NF-κB-dependent pathways. Inflammation 36: 1584-1591.
9. Gingras AC, Gygi SP, Raught B, et al,. 1999. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev 13: 1422-1437.
10. Gingras AC, Raught B, Sonenberg N,. 2001. Regulation of translation initiation by FRAP/mTOR. Genes Dev 15: 807-826.
11. Jiang M, Porat-Shliom Y, Pei Z, et al,. 2010. Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar Parkinsonism. J Neurochem 114: 419-429.
12. Jing K, Lim K,. 2012. Why is autophagy important in human diseases? Exp Mol Med 44: 69-72.
13. Kim J, Kundu M, Viollet B, Guan KL,. 2011. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13: 132-141.
14. Kim SJ, Kim HJ, Kim HR, et al,. 2012. Antitumor actions of baicalein and wogonin in HT-29 human colorectal cancer cells. Mol Med Rep 6: 1443-1449.
15. Kim DH, Hossain MA, Kang YJ, et al,. 2013. Baicalein, an active component of Scutellaria baicalensis Georgi, induces apoptosis in human colon cancer cells and prevents AOM/DSS-induced colon cancer in mice. Int J Oncol 43: 1652-1658.
16. Kumar D, Shankar S, Srivastava RK,. 2014. Rottlerin induces autophagy and apoptosis in prostate cancer stem cells via PI3K/Akt/mTOR signaling pathway. Cancer Lett 343: 179-189.
17. Kuo PL, Hsu YL, Cho CY,. 2006. Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol Cancer Ther 5: 3209-3221.
18. Lee IK, Kang KA, Zhang R, Kim BJ, Kang SS, Hyun JW,. 2011a. Mitochondria protection of baicalein against oxidative damage via induction of manganese superoxide dismutase. Environ Toxicol Pharmacol 31: 233-241.
19. Lee YM, Cheng PY, Chim LS, et al,. 2011b. Baicalein, an active component of Scutellaria baicalensis Georgi, improves cardiac contractile function in endotoxaemic rats via induction of heme oxygenase-1 and suppression of inflammatory responses. J Ethnopharmacol 135: 179-185.
20. Li D, Cui Q, Chen SG, et al,. 2007. Inactivation of ras and changes of mitochondrial membrane potential contribute to oridonin-induced autophagy in a431 cells. J Pharmacol Sci 105: 22-33.
21. Li X, Li X, Wang J, Ye Z, Li JC,. 2012. Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells. Int J Biol Sci 8: 901-912.
22. Li HL, Zhang S, Wang Y, et al,. 2013a. Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells. Mol Med Rep 7: 266-270.
23. Li L, Liu WY, Feng F, Wu CY, Xie N,. 2013b. Synthesis and in vitro cytotoxicity evaluation of baicalein amino acid derivatives. Chin J Nat Med 11: 284-288.
24. Luo R, Wang J, Zhao L, et al,. 2014. Synthesis and biological evaluation of baicalein derivatives as potent antitumor agents. Bioorg Med Chem Lett 24: 1334-1338.
25. Mathew R, White E,. 2007. Why sick cells produce tumors: the protective role of autophagy. Autophagy 3: 502-505.
26. Miocinovic R, McCabe NP, Keck RW, Jankun J, Hampton JA, Selman SH,. 2005. In vivo and in vitro effect of baicalein on human prostate cancer cells. Int J Oncol 26: 241-246.
27. Mujumdar N, Mackenzie TN, Dudeja V, et al,. 2010. Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. Gastroenterology 139: 598-608.
28. Stavniichuk R, Drel VR, Shevalye H, Maksimchyk Y, Kuchmerovska TM, Nadler JL, Obrosova IG,. 2011. Baicalein alleviates diabetic peripheral neuropathy through inhibition of oxidative-nitrosative stress and p38 MAPK activation. Exp Neurol 230: 106-113.
29. Wang Z, Jiang C, Chen W, et al,. 2014. Baicalein induces apoptosis and autophagy via endoplasmic reticulum stress in hepatocellular carcinoma cells. Biomed Res Int 2014: 732516.
30. Wen X, Wu J, Wang F, Liu B, Huang C, Wei Y,. 2013. Deconvoluting the role of reactive oxygen species and autophagy in human diseases. Free Radic Biol Med 65: 402-410.
31. White E,. 2012. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 12: 401-410.
32. Wu JY, Tsai KW, Li YZ, et al,. 2013. Anti-bladder-tumor effect of baicalein from Scutellaria baicalensis georgi and its application in vivo. Evid Based Complement Alternat Med 2013: 579751.
33. Yang Z, Klionsky DJ,. 2010. Eaten alive: a history of macroautophagy. Nat Cell Biol 12: 814-822.
34. Zhang HB, Lu P, Guo QY, Zhang ZH, Meng XY,. 2013a. Baicalein induces apoptosis in esophageal squamous cell carcinoma cells through modulation of the PI3K/Akt pathway. Oncol Lett 5: 722-728.
35. Zhang X, Wei H, Liu Z, et al,. 2013b. A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway. Toxicol Appl Pharmacol 270: 122-128.
36. Zou Y, Ling YH, Sironi J, Schwartz EL, Perez-Soler R, Piperdi B,. 2013. The autophagy inhibitor chloroquine overcomes the innate resistance of wild-type EGFR non-small-cell lung cancer cells to erlotinib. J Thorac Oncol 8: 693-702.