The distinct mechanisms of the antitumor activity of emodin in different types of cancer (Review)

Oncology Reports

Volumn 30, Issue 6, 2013, Pages 2555-2562

  Wei, Wei Tian ^a   Lin, Sheng Zhang ^b   Liu, Dian Lei ^c   Wang, Zhao Hong ^d  

^a ZHEJIANG CANCER HOSPITAL   (China)

^b ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^c Intensive Care Unit   (China)

^d THE SECOND AFFILIATED HOSPITAL AND YUYING CHILDREN S HOSPITAL OF WENZHOU MEDICAL UNIVERSITY   (China)

Author keywords

Cancer; Emodin; Mechanism

Indexed keywords

CARBOPLATIN; CISPLATIN; EMODIN; GEMCITABINE; LIPOSOME; OXALIPLATIN; PACLITAXEL; SILK FIBROIN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL; CANCER COMBINATION CHEMOTHERAPY; CELL GROWTH; CELL PROLIFERATION; COLON CANCER; DRUG CYTOTOXICITY; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG MECHANISM; DRUG RELEASE; DRUG RESPONSE; DRUG STRUCTURE; ESOPHAGUS CANCER; GALLBLADDER CANCER; GROWTH INHIBITION; HUMAN; LIVER CANCER; LUNG NON SMALL CELL CANCER; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; RECEPTOR BLOCKING; STOMACH CANCER; TONGUE CANCER; TONGUE SQUAMOUS CANCER; UTERINE CERVIX CANCER;

ANTINEOPLASTIC AGENTS; APOPTOSIS; COMBINED MODALITY THERAPY; DRUG SYNERGISM; EMODIN; HUMANS; NEOPLASMS; PROTEIN KINASE INHIBITORS;

EID: 84890566867     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or.2013.2741     Document Type: Article

References (64)

1. Chen YC, Shen SC, Lee WR, et al: Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol 64: 1713-1724, 2002.
2. Su YT, Chang HL, Shyue SK and Hsu SL: Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Biochem Pharmacol 70: 229-241, 2005.
3. Srinivas G, Anto RJ, Srinivas P, Vidhyalakshmi S, Senan VP and Karunagaran D: Emodin induces apoptosis of human cervical cancer cells through poly(ADP-ribose) polymerase cleavage and activation of caspase-9. Eur J Pharmacol 473: 117-125, 2003.
4. Huang Q, Shen HM, Shui G, Wenk MR and Ong CN: Emodin inhibits tumor cell adhesion through disruption of the membrane lipid Raft-associated integrin signaling pathway. Cancer Res 66: 5807-5815, 2006.
5. Kwak HJ, Park MJ, Park CM, et al: Emodin inhibits vascular endothelial growth factor-A-induced angiogenesis by blocking receptor-2 (KDR/Flk-1) phosphorylation. Int J Cancer 118: 2711-2720, 2006.
6. Cha TL, Qiu L, Chen CT, Wen Y and Hung MC: Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. Cancer Res 65: 2287-2295, 2005.
7. Muto A, Hori M, Sasaki Y, et al: Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor. Mol Cancer Ther 6: 987-994, 2007.
8. Kim MS, Park MJ, Kim SJ, et al: Emodin suppresses hyaluronic acid-induced MMP-9 secretion and invasion of glioma cells. Int J Oncol 27: 839-846, 2005.
9. Bader Y, Hartmann J, Horvath Z, et al: Synergistic effects of deuterium oxide and gemcitabine in human pancreatic cancer cell lines. Cancer Lett 259: 231-239, 2008.
10. Nakagawa T, Shimizu M, Shirakami Y, et al: Synergistic effects of acyclic retinoid and gemcitabine on growth inhibition in pancreatic cancer cells. Cancer Lett 273: 250-256, 2009.
11. Lee SH, Ryu JK, Lee KY, et al: Enhanced anti-tumor effect of combination therapy with gemcitabine and apigenin in pancreatic cancer. Cancer Lett 259: 39-49, 2008.
12. Wang SJ, Gao Y, Chen H, et al: Dihydroartemisinin inactivates NF-κB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo. Cancer Lett 293: 99-108, 2010.
13. Lin SZ, Wei WT, Chen H, et al: Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis. PLoS One 7: e42146, 2012.
14. Lin SY, Lai WW, Ho CC, et al: Emodin induces apoptosis of human tongue squamous cancer SCC-4 cells through reactive oxygen species and mitochondria-dependent pathways. Anticancer Res 29: 327-335, 2009.
15. Chen YY, Chiang SY, Lin JG, et al: Emodin, aloe-emodin and rhein induced DNA damage and inhibited DNA repair gene expression in SCC-4 human tongue cancer cells. Anticancer Res 30: 945-951, 2010.
16. Chen YY, Chiang SY, Lin JG, et al: Emodin, aloe-emodin and rhein inhibit migration and invasion in human tongue cancer SCC-4 cells through the inhibition of gene expression of matrix metalloproteinase-9. Int J Oncol 36: 1113-1120, 2010.
17. Cai J, Niu X, Chen Y, et al: Emodin-induced generation of reactive oxygen species inhibits RhoA activation to sensitize gastric carcinoma cells to anoikis. Neoplasia 10: 41-51, 2008.
18. Sun ZH and Bu P: Downregulation of phosphatase of regenerating liver-3 is involved in the inhibition of proliferation and apoptosis induced by emodin in the SGC-7901 human gastric carcinoma cell line. Exp Ther Med 3: 1077-1081, 2012.
19. Wang QJ, Cai XB, Liu MH, Hu H, Tan XJ and Jing XB: Apoptosis induced by emodin is associated with alterations of intracellular acidification and reactive oxygen species in EC-109 cells. Biochem Cell Biol 88: 767-774, 2010.
20. Hsu CM, Hsu YA, Tsai Y, et al: Emodin inhibits the growth of hepatoma cells: finding the common anti-cancer pathway using Huh7, Hep3B, and HepG2 cells. Biochem Biophys Res Commun 392: 473-478, 2010.
21. Yu JQ, Bao W and Lei JC: Emodin regulates apoptotic pathway in human liver cancer cells. Phytother Res 27: 251-257, 2012.
22. Kim MJ, Oh DY, Lee SH, et al : Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study. BMC Cancer 8: 374, 2008.
23. Wang W, Sun YP, Huang XZ, et al: Emodin enhances sensitivity of gallbladder cancer cells to platinum drugs via glutathion depletion and MRP1 downregulation. Biochem Pharmacol 79: 1134-1140, 2010.
24. Trachootham D, Alexandre J and Huang P: Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8: 579-591, 2009.
25. Wang J and Yi J: Cancer cell killing via ROS: to increase or decrease, that is the question. Cancer Biol Ther 7: 1875-1884, 2008.
26. Wang W, Sun Y, Li X, et al: Emodin potentiates the anticancer effect of cisplatin on gallbladder cancer cells through the generation of reactive oxygen species and the inhibition of survivin expression. Oncol Rep 26: 1143-1148, 2011.
27. Moserle L, Ghisi M, Amadori A and Indraccolo S: Side population and cancer stem cells: therapeutic implications. Cancer Lett 288: 1-9, 2010.
28. Wu C and Alman BA: Side population cells in human cancers. Cancer Lett 268: 1-9, 2008.
29. Tabor MH, Clay MR, Owen JH, et al: Head and neck cancer stem cells: the side population. Laryngoscope 121: 527-533, 2011.
30. Li XX, Wang J, Wang HL, et al: Characterization of cancer stem-like cells derived from a side population of a human gall-bladder carcinoma cell line, SGC-996. Biochem Biophys Res Commun 419: 728-734, 2012.
31. Li XX, Ding Y, Wang W, et al: Emodin as an effective agent in targeting cancer stem-like side population cells of gallbladder carcinoma. Stem Cells Dev 22: 554-566, 2012.
32. Lu Y, Zhang J and Qian J: The effect of emodin on VEGF receptors in human colon cancer cells. Cancer Biother Radiopharm 23: 222-228, 2008.
33. Ma YS, Weng SW, Lin MW, et al: Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: roles of apoptotic cell death and LS1034 tumor xenografts model. Food Chem Toxicol 50: 1271-1278, 2012.
34. Saha S, Bardelli A, Buckhaults P, et al: A phosphatase associated with metastasis of colorectal cancer. Science 294: 1343-1346, 2001.
35. Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N and Watanabe M: Phosphatase of regenerating liver-3 as a convergent therapeutic target for lymph node metastasis in esophageal squamous cell carcinoma. Int J Cancer 127: 543-554, 2010.
36. Han YM, Lee SK, Jeong DG, et al: Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of PRL-3 phosphatase activity. Bioorg Med Chem Lett 22: 323-326, 2012.
37. Damodharan U, Ganesan R and Radhakrishnan UC: Expression of MMP2 and MMP9 (gelatinases A and B) in human colon cancer cells. Appl Biochem Biotechnol 165: 1245-1252, 2011.
38. Guo Q, Chen Y, Zhang B, Kang M, Xie Q and Wu Y: Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition. Biochem Pharmacol 77: 1674-1683, 2009.
39. Chen H, Wei W, Guo Y, et al: Enhanced effect of gemcitabine by emodin against pancreatic cancer in vivo via cytochrome C-regulated apoptosis. Oncol Rep 25: 1253-1261, 2011.
40. Liu JX, Zhang JH, Li HH, et al: Emodin induces Panc-1 cell apoptosis via declining the mitochondrial membrane potential. Oncol Rep 28: 1991-1996, 2012.
41. Liu A, Chen H, Wei W, et al: Antiproliferative and antimetastatic effects of emodin on human pancreatic cancer. Oncol Rep 26: 81-89, 2011.
42. Wei WI, Chen H, Ni ZL, et al: Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation. Int J Oncol 39: 1381-1390, 2011.
43. Liu DL, Bu H, Li H, et al: Emodin reverses gemcitabine resistance in pancreatic cancer cells via the mitochondrial apoptosis pathway in vitro. Int J Oncol 40: 1049-1057, 2012.
44. Guo HC, Bu HQ, Luo J, et al: Emodin potentiates the antitumor effects of gemcitabine in PANC-1 pancreatic cancer xenograft model in vivo via inhibition of inhibitors of apoptosis. Int J Oncol 40: 1849-1857, 2012.
45. Chen RS, Jhan JY, Su YJ, et al: Emodin enhances gefitinib-induced cytotoxicity via Rad51 downregulation and ERK1/2 inactivation. Exp Cell Res 315: 2658-2672, 2009.
46. Liu B, Chen Y and St Clair DK: ROS and p53: a versatile partnership. Free Radic Biol Med 44: 1529-1535, 2008.
47. Lai JM, Chang JT, Wen CL and Hsu SL: Emodin induces a reactive oxygen species-dependent and ATM-p53-Bax mediated cytotoxicity in lung cancer cells. Eur J Pharmacol 623: 1-9, 2009
48. Ko JC, Su YJ, Lin ST, et al: Suppression of ERCC1 and Rad51 expression through ERK1/2 inactivation is essential in emodin-mediated cytotoxicity in human non-small cell lung cancer cells. Biochem Pharmacol 79: 655-664, 2010.
49. Ko JC, Su YJ, Lin ST, et al: Emodin enhances cisplatin-induced cytotoxicity via down-regulation of ERCC1 and inactivation of ERK1/2. Lung Cancer 69: 155-164, 2010.
50. Su YJ, Tsai MS, Kuo YH, et al: Role of Rad51 down-regulation and extracellular signal-regulated kinases 1 and 2 inactivation in emodin and mitomycin C-induced synergistic cytotoxicity in human non-small-cell lung cancer cells. Mol Pharmacol 77: 633-643, 2010.
51. Ko JC, Tsai MS, Kuo YH, et al: Modulation of Rad51, ERCC1, and thymidine phosphorylase by emodin result in synergistic cytotoxic effect in combination with capecitabine. Biochem Pharmacol 81: 680-690, 2011.
52. He L, Bi JJ, Guo Q, Yu Y and Ye XF: Effects of emodin extracted from Chinese herbs on proliferation of non-small cell lung cancer and underlying mechanisms. Asian Pac J Cancer Prev 13: 1505-1510, 2012.
53. Cheema SK, Gobin AS, Rhea R, Lopez-Berestein G, Newman RA and Mathur AB: Silk fibroin mediated delivery of liposomal emodin to breast cancer cells. Int J Pharm 341: 221-229, 2007.
54. Huang Z, Chen G and Shi P: Emodin-induced apoptosis in human breast cancer BCap-37 cells through the mitochondrial signaling pathway. Arch Pharm Res 31: 742-748, 2008.
55. Huang Z, Chen G and Shi P: Effects of emodin on the gene expression profiling of human breast carcinoma cells. Cancer Detect Prev 32: 286-291, 2009.
56. Wang S, Chen T, Chen R, Hu Y, Chen M and Wang Y: Emodin loaded solid lipid nanoparticles: preparation, characterization and antitumor activity studies. Int J Pharm 430: 238-246, 2012.
57. Olsen BB, Bjorling-Poulsen M and Guerra B: Emodin negatively affects the phosphoinositide 3-kinase/AKT signalling pathway: a study on its mechanism of action. Int J Biochem Cell Biol 39: 227-237, 2007.
58. Huang XZ, Wang J, Huang C, et al: Emodin enhances cytotoxicity of chemotherapeutic drugs in prostate cancer cells: the mechanisms involve ROS-mediated suppression of multidrug resistance and hypoxia inducible factor-1. Cancer Biol Ther 7: 468-475, 2008.
59. Yu CX, Zhang XQ, Kang LD, et al: Emodin induces apoptosis in human prostate cancer cell LNCaP. Asian J Androl 10: 625-634, 2008.
60. Ok S, Kim SM, Kim C, et al: Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4. Immunopharmacol Immunotoxicol 4: 768-778, 2012.
61. Li J, Liu P, Mao H, Wanga A and Zhang X: Emodin sensitizes paclitaxel-resistant human ovarian cancer cells to paclitaxel-induced apoptosis in vitro. Oncol Rep 21: 1605-1610, 2009.
62. Kurokawa T, He G and Siddik ZH: Protein kinase inhibitors emodin and dichloro-ribofuranosylbenzimidazole modulate the cellular accumulation and cytotoxicity of cisplatin in a schedule-dependent manner. Cancer Chemother Pharmacol 65: 427-436, 2010.
63. Brown M, Bellon M and Nicot C: Emodin and DHA potently increase arsenic trioxide interferon-α-induced cell death of HTLV-I-transformed cells by generation of reactive oxygen species and inhibition of Akt and AP-1. Blood 109: 1653-1659, 2007.
64. Wang C-G, Yang J-Q, Liu B-Z, et al: Anti-tumor activity of emodin against human chronic myelocytic leukemia K562 cell lines in vitro and in vivo. Eur J Pharmacol 627: 33-41, 2010.