Kaempferol induces autophagy through AMPK and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells

International Journal of Oncology

Volumn 42, Issue 6, 2013, Pages 2069-2077

  Huang, Wen Wen ^a   Tsai, Shih Chang ^a   Peng, Shu Fen ^a   Lin, Meng Wei ^b   Chiang, Jo Hua ^c   Chiu, Yu Jen ^d   Fushiya, Shinji ^e   Tseng, Michael T ^f   Yang, Jai Sing ^a  

^a CHINA MEDICAL UNIVERSITY   (Taiwan)

^b CARDINAL TIEN COLLEGE OF HEALTHCARE AND MANAGEMENT   (Taiwan)

^c NATIONAL CHUNG HSING UNIVERSITY   (Taiwan)

^d TAIPEI VETERANS GENERAL HOSPITAL   (Taiwan)

^e NIHON PHARMACEUTICAL UNIVERSITY   (Japan)

^f University of Louisville School of Medicine   (United States)

Author keywords

AKT; AMPK; Autophagy; Kaempferol; SK HEP 1 human hepatic cancer cells

Indexed keywords

BECLIN 1; CASPASE 3; CYCLIN B; CYCLIN DEPENDENT KINASE 1; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; KAEMPFEROL; MAMMALIAN TARGET OF RAPAMYCIN; MICROTUBULE ASSOCIATED PROTEIN 1; PROTEIN KINASE B; THYMOCYTE ANTIBODY;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGY; CELL DEATH; CELL ORGANELLE; CELL VACUOLE; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA FRAGMENTATION; DOWN REGULATION; DRUG CYTOTOXICITY; ENZYME ACTIVITY; G2 PHASE CELL CYCLE CHECKPOINT; GEL ELECTROPHORESIS; HUMAN; HUMAN CELL; LIGHT CHAIN; LIVER CANCER; LYSOSOME; M PHASE CELL CYCLE CHECKPOINT; PRIORITY JOURNAL; PROTEIN CLEAVAGE; TRANSMISSION ELECTRON MICROSCOPY;

AMP-ACTIVATED PROTEIN KINASES; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; AUTOPHAGY; CASPASE 3; CDC2 PROTEIN KINASE; CELL SURVIVAL; CYCLIN B; DOWN-REGULATION; HUMANS; KAEMPFEROLS; LIVER NEOPLASMS; MICROTUBULE-ASSOCIATED PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; TOR SERINE-THREONINE KINASES; TUMOR CELLS, CULTURED;

EID: 84876543464     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2013.1909     Document Type: Article

References (37)

1. Gong JH, Shin D, Han SY, et al: Kaempferol suppresses eosion-phil infltration and airway infammation in airway epithelial cells and in mice with allergic asthma. J Nutr 142: 47-56, 2012.
2. Huang W W, Chiu YJ, Fan MJ, et al: Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathway in human osteosarcoma U-2 OS cells. Mol Nutr Food Res 54: 1585-1595, 2010.
3. Sharma V, Joseph C, Ghosh S, et al: Kaempferol induces apoptosis in glioblastoma cells through oxidative stress. Mol Cancer Ther 6: 2544-2553, 2007. (Pubitemid 47480420)
4. Samhan-Arias AK, Martin-Romero FJ and Gutierrez-Merino C: Kaempferol blocks oxidative stress in cerebellar granule cells and reveals a key role for reactive oxygen species production at the plasma membrane in the commitment to apoptosis. Free Radic Biol Med 37: 48-61, 2004. (Pubitemid 38746650)
5. Choi EJ and Ahn WS: Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells. Nutr Res Pract 2: 322-325, 2008.
6. Tsiklauri L, An G, Ruszaj DM, et al: Simultaneous determination of the favonoids robinin and kaempferol in human breast cancer cells by liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal 55: 109-113, 2011.
7. Nguyen TT, Tran E, Ong CK, et al: Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. J Cell Physiol 197: 110-121, 2003. (Pubitemid 37486233)
8. Li W, Du B, Wang T, et al: Kaempferol induces apoptosis in human HCT116 colon cancer cells via the Ataxia-telangiectasia mutated-p53 pathway with the involvement of p53 upregulated modulator of apoptosis. Chem Biol Interact 177: 121-127, 2009.
9. Yoshida T, Konishi M, Horinaka M, et al: Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem Biophys Res Commun 375: 129-133, 2008.
10. Benyahia S, Benayache S, Benayache F, et al: Isolation from Eucalyptus occidentalis and identifcation of a new kaempferol derivative that induces apoptosis in human myeloid leukemia cells. J Nat Prod 67: 527-531, 2004. (Pubitemid 38533920)
11. Tsai SC, Yang JS, Peng SF, et al: Bufalin increases sensitivity to AKT/mTOR-induced autophagic cell death in SK-HEP-1 human hepatocellular carcinoma cells. Int J Oncol 41: 1431-1442, 2012.
12. Jiang W and Ogretmen B: Ceramide stress in survival versus lethal autophagy paradox: ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Autophagy 9: 258-259, 2013.
13. Tumbarello DA, Waxse BJ, Arden SD, et al: Autophagy receptors link myosin VI to autophagosomes to mediate Tom1-dependent autophagosome maturation and fusion with the lysosome. Nat Cell Biol 14: 1024-1035, 2012.
14. Orsi A, Razi M, Dooley HC, et al: Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell 23: 1860-1873, 2012.
15. Son SM, Song H, Byun J, et al: Accumulation of auto phago some scontributes to enhanced amyloidogenic APP processing under insulin-resistant conditions. Autophagy 8: 1842-1844, 2012.
16. Pan L, Li Y, Jia L, et al: Cathepsin S deficiency results in abnormal accumulation of autophagosomes in macrophages and enhances Ang II-induced cardiac infammation. PLoS One 7: e35315, 2012.
17. Griffths RE, Kupzig S, Cogan N, et al: Maturing reticulocytes internalize plasma membrane in glycophorin A-containing vesicles that fuse with autophagosomes before exocytosis. Blood 119: 6296-6306, 2012.
18. Mijaljica D, Prescott M and Devenish RJ: The intriguing life of autophagosomes. Int J Mol Sci 13: 3618-3635, 2012.
19. Gabrielska J, Soczynska-Kordala M and Przestalski S: Antioxidative effect of kaempferol and its equimolar mixture with phenyltin compounds on UV-irradiated liposome membranes. J Agric Food Chem 53: 76-83, 2005. (Pubitemid 40066473)
20. Hamalainen M, Nieminen R, Vuorela P, Heinonen M and Moilanen E: A nti-infam mator y effects of favonoids: gen istein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas favone, isorhamnetin, narin-genin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Infamm 2007: 45673, 2007.
21. Garcia-Mediavilla V, Crespo I, Collado PS, et al: The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur J Pharmacol 557: 221-229, 2007. (Pubitemid 46186282)
22. Lan YH, Chiang JH, Huang WW, et al: Activations of both extrinsic and intrinsic pathways in HCT 116 human colorectal cancer cells contribute to apoptosis through p53-mediated ATM/Fas signaling by Emilia sonchifolia extract, a folklore medicinal plant. Evid Based Complement Alternat Med 2012: 178178, 2012.
23. Tsai SC, Huang W W, Huang WC, et al: ERK-modulated intrinsic signaling and G(2)/M phase arrest contribute to the induction of apoptotic death by allyl isothiocyanate in MDA-MB-468 human breast adenocarcinoma cells. Int J Oncol 41: 2065-2072, 2012.
24. Chiang JH, Yang JS, Ma CY, et al: Danthron, an anthraquinone derivative, induces DNA damage and caspase cascades-mediated apoptosis in SNU-1 human gastric cancer cells through mitochondrial permeability transition pores and Bax-triggered pathways. Chem Res Toxicol 24: 20-29, 2011.
25. Huang WW, Ko SW, Tsai HY, et al: Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways. Int J Oncol 38: 1067-1073, 2011.
26. Lu CC, Yang JS, Huang AC, et al: Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Mol Nutr Food Res 54: 967-976, 2010.
27. Chiu YJ, Hour MJ, Lu CC, et al: Novel quinazoline HMJ-30 induces U-2 OS human osteogenic sarcoma cell apoptosis through induction of oxidative stress and up-regulation of ATM/p53 signaling pathway. J Orthop Res 29: 1448-1456, 2011.
28. Lu CC, Yang JS, Chiang JH, et al: Novel quinazolinone MJ-29 triggers endoplasmic reticulum stress and intrinsic apoptosis in murine leukemia WEHI-3 cells and inhibits leukemic mice. PLoS One 7: e36831, 2012.
29. Luo H, Rankin GO, Li Z, et al: Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway. Food Chem 128: 513-519, 2011.
30. Luo H, Jiang B, Li B, et al: Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability. Int J Nanomed 7: 3951-3959, 2012.
31. Bandyopadhyay S, Romero JR and Chattopadhyay N: Kaempferol and quercetin stimulate granulocyte-macrophage colony-stimulating factor secretion in human prostate cancer cells. Mol Cell Endocrinol 287: 57-64, 2008.
32. Edinger AL and Thompson CB: Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16: 663-669, 2004. (Pubitemid 39463117)
33. Filomeni G, Desideri E, Cardaci S, et al: Carcinoma cells activate AMP-activated protein kinase-dependent autophagy as survival response to kaempferol-mediated energetic impairment. Autophagy 6: 202-216, 2010.
34. Park SE, Sapkota K, Kim S, et al: Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells. Br J of Pharmacol 164: 1008-1025, 2011.
35. Vucicevic L, Misirkic M, Janjetovic K, et al: Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. Autophagy 7: 40-50, 2011.
36. Liu H, Xu L, He H, et al: Hepatitis B virus X protein promotes hepatoma cell invasion and metastasis by stabilizing Snail protein. Cancer Sci 103: 2072-2081, 2012.
37. Luo H, Rankin GO, Juliano N, et al: Kaempferol inhibits VEGF expression and in vitro angiogenesis through a novel ERK-NFκB-cMyc-p21 pathway. Food Chem 130: 321-328, 2012.