Ursolic acid promotes cancer cell death by inducing Atg5-dependent autophagy

International Journal of Cancer

Volumn 133, Issue 12, 2013, Pages 2781-2790

  Leng, Shuilong ^a   Hao, Yanli ^a   Du, Daobing ^a   Xie, Shanyan ^a   Hong, Lepeng ^a   Gu, Haigang ^a   Zhu, Xiao ^b   Zhang, Jinfang ^b   Fan, Daping ^c   Kung, Hsiang Fu ^b  

^a GUANGZHOU MEDICAL UNIVERSITY   (China)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^c UNIVERSITY OF SOUTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

apoptosis; Atg5; autophagy; TC 1; ursolic acid

Indexed keywords

AUTOPHAGY PROTEIN 5; BECLIN 1; IMMUNOGLOBULIN LIGHT CHAIN; IMMUNOGLOBULIN LIGHT CHAIN 3; SMALL INTERFERING RNA; TETRAZOLIUM; UNCLASSIFIED DRUG; URSOLIC ACID; WORTMANNIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CANCER CELL; CANCER INHIBITION; CELL DEATH; CELL SURVIVAL; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA FRAGMENTATION; DRUG CYTOTOXICITY; EMBRYO; FEMALE; FIBROBLAST; FLOW CYTOMETRY; GENE EXPRESSION; HISTOPATHOLOGY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; TRANSMISSION ELECTRON MICROSCOPY; TUMOR VOLUME; UTERINE CERVIX CANCER; WESTERN BLOTTING;

APOPTOSIS; ATG5; AUTOPHAGY; TC-1; URSOLIC ACID;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; FEMALE; HELA CELLS; HUMANS; MEMBRANE PROTEINS; MICE; MICE, INBRED C57BL; MICROTUBULE-ASSOCIATED PROTEINS; TRITERPENES;

EID: 84885617480     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.28301     Document Type: Article

References (46)

1. Mizushima N, Levine B, Cuervo AM, et al,. Autophagy fights disease through cellular self-digestion. Nature 2008; 451: 1069-75.
2. Arsov I, Li X, Matthews G, et al,. BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development. Cell Death Differ 2008; 15: 1385-95.
3. Mizushima N, Yamamoto A, Hatano M, et al,. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol 2001; 152: 657-68.
4. Kuma A, Hatano M, Matsui M, et al,. The role of autophagy during the early neonatal starvation period. Nature 2004; 432: 1032-6.
5. Mathew R, Kongara S, Beaudoin B, et al,. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 2007; 21: 1367-81.
6. McPhee CK, Logan MA, Freeman MR, et al,. Activation of autophagy during cell death requires the engulfment receptor Draper. Nature 2010; 465: 1093-6.
7. Li P, Du Q, Cao Z, et al,. Interferon-gamma induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF-1). Cancer Lett 2012; 314: 213-22.
8. Zhou F, Yang Y, Xing D,. Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. FEBS J 2011; 278: 403-13.
9. Chi S, Kitanaka C, Noguchi K, et al,. Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells. Oncogene 1999; 18: 2281-90.
10. Kim KH, Seo HS, Choi HS, et al,. Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells. Arch Pharm Res 2011; 34: 1363-72.
11. Ikeda Y, Murakami A, Ohigashi H,. Ursolic acid: an anti- and pro-inflammatory triterpenoid. Mol Nutr Food Res 2008; 52: 26-42.
12. Sohn KH, Lee HY, Chung HY, et al,. Anti-angiogenic activity of triterpene acids. Cancer Lett 1995; 94: 213-8.
13. Shyu MH, Kao TC, Yen GC,. Oleanolic acid and ursolic acid induce apoptosis in HuH7 human hepatocellular carcinoma cells through a mitochondrial-dependent pathway and downregulation of XIAP. J Agric Food Chem 2010; 58: 6110-8.
14. Li Y, Xing D, Chen Q, et al,. Enhancement of chemotherapeutic agent-induced apoptosis by inhibition of NF-kappaB using ursolic acid. Int J Cancer 2010; 127: 462-73.
15. Shanmugam MK, Rajendran P, Li F, et al,. Ursolic acid inhibits multiple cell survival pathways leading to suppression of growth of prostate cancer xenograft in nude mice. J Mol Med 2011; 89: 713-27.
16. Kassi E, Sourlingas TG, Spiliotaki M, et al,. Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Invest 2009; 27: 723-33.
17. Xavier CP, Lima CF, Preto A, et al,. Luteolin, quercetin and ursolic acid are potent inhibitors of proliferation and inducers of apoptosis in both KRAS and BRAF mutated human colorectal cancer cells. Cancer Lett 2009; 281: 162-70.
18. Yim EK, Lee KH, Namkoong SE, et al,. Proteomic analysis of ursolic acid-induced apoptosis in cervical carcinoma cells. Cancer Lett 2006; 235: 209-20.
19. Bursch W, Ellinger A, Kienzl H, et al,. Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis 1996; 17: 1595-607.
20. Kanzawa T, Kondo Y, Ito H, et al,. Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. Cancer Res 2003; 63: 2103-8.
21. Opipari AW, Jr, Tan L, Boitano AE, et al,. Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res 2004; 64: 696-703.
22. Ellington AA, Berhow M, Singletary KW,. Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins. Carcinogenesis 2005; 26: 159-67.
23. Sharma RK, Elpek KG, Yolcu ES, et al,. Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel form of 4-1BB ligand eradicates established tumors. Cancer Res 2009; 69: 4319-26.
24. Yim EK, Lee MJ, Lee KH, et al,. Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines. Int J Gynecol Cancer 2006; 16: 2023-31.
25. Prasad S, Yadav VR, Kannappan R, et al,. Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-independent up-regulation of death receptors: evidence for the role of reactive oxygen species and JNK. J Biol Chem 2011; 286: 5546-57.
26. Yang L, Liu X, Lu Z, et al,. Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor. Cancer Lett 2011; 298: 128-38.
27. Huang CY, Lin CY, Tsai CW, et al,. Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines. Toxicol In Vitro 2011; 25: 1274-80.
28. Pozuelo-Rubio M,. Regulation of autophagic activity by 14-3-3zeta proteins associated with class III phosphatidylinositol-3-kinase. Cell Death Differ 2010; 18: 479-92.
29. Manov I, Pollak Y, Broneshter R, et al,. Inhibition of doxorubicin-induced autophagy in hepatocellular carcinoma Hep3B cells by sorafenib-the role of extracellular signal-regulated kinase counteraction. FEBS J 2011; 278: 3494-507.
30. Wu YT, Tan HL, Huang Q, et al,. Activation of the PI3K-Akt-mTOR signaling pathway promotes necrotic cell death via suppression of autophagy. Autophagy 2009; 5: 824-34.
31. Ito S, Koshikawa N, Mochizuki S, et al,. 3-Methyladenine suppresses cell migration and invasion of HT1080 fibrosarcoma cells through inhibiting phosphoinositide 3-kinases independently of autophagy inhibition. Int J Oncol 2007; 31: 261-8.
32. Alaimo PJ, Knight ZA, Shokat KM,. Targeting the gatekeeper residue in phosphoinositide 3-kinases. Bioorg Med Chem 2005; 13: 2825-36.
33. Tanida I, Minematsu-Ikeguchi N, Ueno T, et al,. Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy 2005; 1: 84-91.
34. Mizushima N, Yoshimori T,. How to interpret LC3 immunoblotting. Autophagy 2007; 3: 542-5.
35. Ganapathy E, Su F, Meriwether D, et al,. D-4F, an apoA-I mimetic peptide, inhibits proliferation and tumorigenicity of epithelial ovarian cancer cells by upregulating the antioxidant enzyme MnSOD. Int J Cancer 2011; 130: 1071-81.
36. Przybyla BD, Shafirstein G, Koonce NA, et al,. Conductive thermal ablation of 4T1 murine breast carcinoma reduces severe hypoxia in surviving tumour. Int J Hyperthermia 2012; 28: 156-62.
37. Pyo JO, Jang MH, Kwon YK, et al,. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem 2005; 280: 20722-9.
38. Byun JY, Yoon CH, An S, et al,. The Rac1/MKK7/JNK pathway signals upregulation of Atg5 and subsequent autophagic cell death in response to oncogenic Ras. Carcinogenesis 2009; 30: 1880-8.
39. Jiang ZF, Shao LJ, Wang WM, et al,. Decreased expression of Beclin-1 and LC3 in human lung cancer. Mol Biol Rep 2012; 39: 259-67.
40. Won KY, Kim GY, Lim SJ, et al,. Decreased Beclin-1 expression is correlated with the growth of the primary tumor in patients with squamous cell carcinoma and adenocarcinoma of the lung. Hum Pathol 2012; 43: 62-8.
41. Cheng HY, Zhang YN, Wu QL, et al,. Expression of beclin 1, an autophagy-related protein, in human cervical carcinoma and its clinical significance. Eur J Gynaecol Oncol 2012; 33: 15-20.
42. Grishchuk Y, Ginet V, Truttmann AC, et al,. Beclin 1-independent autophagy contributes to apoptosis in cortical neurons. Autophagy 2011; 7: 1115-31.
43. Scarlatti F, Maffei R, Beau I, et al,. Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell Death Differ 2008; 15: 1318-29.
44. Zhu JH, Horbinski C, Guo F, et al,. Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4- phenylpyridinium-induced cell death. Am J Pathol 2007; 170: 75-86.
45. Smith DM, Patel S, Raffoul F, et al,. Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells. Cell Death Differ 2010; 17: 1867-81.
46. Raffoul F, Campla C, Nanjundan M,. SnoN/SkiL, a TGFbeta signaling mediator: a participant in autophagy induced by arsenic trioxide. Autophagy 2010; 6: 955-7.