Podophyllotoxin acetate triggers anticancer effects against non-small cell lung cancer cells by promoting cell death via cell cycle arrest, ER stress and autophagy

International Journal of Oncology

Volumn 47, Issue 4, 2015, Pages 1257-1265

  Choi, Jae Yeon ^a   Hong, Wan Gi ^a   Cho, Jeong Hyun ^a   Kim, Eun Mi ^a   Kim, Jongdoo ^a   Jung, Chan Hun ^a   Hwang, Sang Gu ^a   Um, Hong Duck ^a   Park, Jong Kuk ^a  

^a Korea Institute of Radiation and Medical Science   (South Korea)

Author keywords

Apoptosis; Autophagy; Cell cycle arrest; ER stress; Lung cancer; Podophyllotoxin acetate

Indexed keywords

ANTINEOPLASTIC AGENT; AURORA B KINASE; AUTOPHAGY PROTEIN 3; AUTOPHAGY PROTEIN 5; AUTOPHAGY PROTEIN 7; BECLIN 1; CASPASE 3; CASPASE 8; CASPASE 9; CYCLIN B1; CYCLIN DEPENDENT KINASE 1; GLUCOSE REGULATED PROTEIN 78; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; HISTONE H2AX; JANUS KINASE; PODOPHYLLOTOXIN ACETATE; PROTEIN IRE1; PROTEIN P21; SURVIVIN; UNCLASSIFIED DRUG; PODOPHYLLOTOXIN;

ANTINEOPLASTIC ACTIVITY; ARTICLE; AUTOPHAGY; CELL DEATH; DNA DAMAGE; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVATION; FLUORESCENCE ACTIVATED CELL SORTING; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOCYTOCHEMISTRY; MICROTUBULE ASSEMBLY; NON SMALL CELL LUNG CANCER; PRIORITY JOURNAL; PROTEIN CLEAVAGE; APOPTOSIS; CELL CYCLE CHECKPOINT; DRUG EFFECTS; IMMUNOHISTOCHEMISTRY; LUNG TUMOR; MICROTUBULE; PATHOLOGY; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; AUTOPHAGY; CARCINOMA, NON-SMALL-CELL LUNG; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; ENDOPLASMIC RETICULUM STRESS; HUMANS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; LUNG NEOPLASMS; MICROTUBULES; PODOPHYLLOTOXIN;

EID: 84940987182     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2015.3123     Document Type: Article

References (26)

1. Cragg GM, Grothaus PG and Newman DJ: Impact of natural products on developing new anti-cancer agents. Chem Rev 109: 3012-3043, 2009.
2. Gordaliza M, García PA, del Corral JM, Castro MA and Gómez-Zurita MA: Podophyllotoxin: Distribution, sources, applications and new cytotoxic derivatives. Toxicon 44: 441-459, 2004.
3. Guerram M, Jiang Z-Z and Zhang L-Y: Podophyllotoxin, a medicinal agent of plant origin: Past, present and future. Chin J Nat Med 10: 161-169, 2012.
4. Choi JY, Cho HJ, Hwang SG, Kim WJ, Kim JI, Um HD and Park JK: Podophyllotoxin acetate enhances γ-ionizing radiationinduced apoptotic cell death by stimulating the ROS/p38/caspase pathway. Biomed Pharmacother 70: 111-118, 2015.
5. Kuo CC, Hsieh HP, Pan WY, Chen CP, Liou JP, Lee SJ, Chang YL, Chen LT, Chen CT and Chang JY: BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res 64: 4621-4628, 2004.
6. Park JK, Jung HY, Park SH, Kang SY, Yi MR, Um HD and Hong SH: Combination of PTEN and gamma-ionizing radiation enhances cell death and G(2)/M arrest through regulation of AKT activity and p21 induction in non-small-cell lung cancer cells. Int J Radiat Oncol Biol Phys 70: 1552-1560, 2008.
7. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin 58: 71-96, 2008.
8. Begg AC, Stewart FA and Vens C: Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 11: 239-253, 2011.
9. Tsai CM, Chang KT, Perng RP, Mitsudomi T, Chen MH, Kadoyama C and Gazdar AF: Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations. J Natl Cancer Inst 85: 897-901, 1993.
10. Xin Y, Yin F, Qi S, Shen L, Xu Y, Luo L, Lan L and Yin Z: Parthenolide reverses doxorubicin resistance in human lung carcinoma A549 cells by attenuating NF-κB activation and HSP70 up-regulation. Toxicol Lett 221: 73-82, 2013.
11. Breen L, Heenan M, Amberger-Murphy V and Clynes M: Investigation of the role of p53 in chemotherapy resistance of lung cancer cell lines. Anticancer Res 27A: 1361-1364, 2007.
12. Jung IL, Kang HJ, Kim KC and Kim IG: PTEN/pAkt/p53 signaling pathway correlates with the radioresponse of non-small cell lung cancer. Int J Mol Med 25: 517-523, 2010.
13. Jordan MA and Wilson L: Microtubules as a target for anticancer drugs. Nat Rev Cancer 4: 253-265, 2004.
14. Montecucco A and Biamonti G: Cellular response to etoposide treatment. Cancer Lett 252: 9-18, 2007.
15. Kaufmann SH: Cell death induced by topoisomerase-targeted drugs: More questions than answers. Biochim Biophys Acta 1400: 195-211, 1998.
16. Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol 35: 495-516, 2007.
17. Bicknell AA, Babour A, Federovitch CM and Niwa M: A novel role in cytokinesis reveals a housekeeping function for the unfolded protein response. J Cell Biol 177: 1017-1027, 2007.
18. Chen JY, Tang YA, Li WS, Chiou YC, Shieh JM and Wang YC: A synthetic podophyllotoxin derivative exerts anti-cancer effects by inducing mitotic arrest and pro-apoptotic ER stress in lung cancer preclinical models. PLoS One 8: e62082, 2013.
19. Schröder M and Kaufman RJ: ER stress and the unfolded protein response. Mutat Res 569: 29-63, 2005.
20. Gills JJ, Lopiccolo J and Dennis PA: Nelfinavir, a new anti-cancer drug with pleiotropic effects and many paths to autophagy. Autophagy 4: 107-109, 2008.
21. Terés S, Lladó V, Higuera M, Barceló-Coblijn G, Martin ML, Noguera-Salv MA, Marcilla-Etxenike A, García-Verdugo JM, Soriano-Navarro M, Saus C, et al: 2-Hydroxyoleate, a nontoxic membrane binding anticancer drug, induces glioma cell differentiation and autophagy. Proc Natl Acad Sci USA 109: 8489-8494, 2012.
22. Galluzzi L, Pietrocola F, Levine B and Kroemer G: Metabolic control of autophagy. Cell 159: 1263-1276, 2014.
23. Yang ZJ, Chee CE, Huang S and Sinicrope FA: The role of autophagy in cancer: Therapeutic implications. Mol Cancer Ther 10: 1533-1541, 2011.
24. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, et a: Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8: 445-544, 2012.
25. Yan CH, Yang YP, Qin ZH, Gu ZL, Reid P and Liang ZQ: Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells. Acta Pharmacol Sin 28: 540-548, 2007.
26. Abedin MJ, Wang D, McDonnell MA, Lehmann U and Kelekar A: Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death Differ 14: 500-510, 2007.