Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer

Toxicology Letters

Volumn 222, Issue 1, 2013, Pages 23-35

  Bao, Guo Qing ^a   Shen, Bai Yong ^a   Pan, Chun Peng ^a   Zhang, Ya Jing ^a   Shi, Min Min ^a   Peng, Cheng Hong ^a  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

Akt; Andrographolide; Gemcitabine; Pancreatic cancer; STAT3

Indexed keywords

ANDROGRAPHOLIDE; CYCLIN D1; CYCLIN E; GEMCITABINE; PROTEIN BAX; PROTEIN BCL 2; PROTEIN KINASE B; PROTEIN P21; STAT3 PROTEIN; SURVIVIN; X LINKED INHIBITOR OF APOPTOSIS;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CELL CYCLE ARREST; CELL CYCLE REGULATION; CELL PROLIFERATION; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG POTENTIATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; TIME; UPREGULATION;

AKT; ANDROGRAPHOLIDE; GEMCITABINE; PANCREATIC CANCER; STAT3;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; BLOTTING, WESTERN; CELL COUNT; CELL CYCLE; CELL LINE, TUMOR; COLORING AGENTS; CYTOCHROMES C; DEOXYCYTIDINE; DITERPENES; DRUG SYNERGISM; FLOW CYTOMETRY; GENTIAN VIOLET; HUMANS; KI-67 ANTIGEN; MALE; MICE; MICE, INBRED BALB C; PANCREATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; STAT3 TRANSCRIPTION FACTOR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84881227758     PISSN: 03784274     EISSN: 18793169     Source Type: Journal    
DOI: 10.1016/j.toxlet.2013.06.241     Document Type: Article

References (54)

1. Ahmad K., Biersack B., Li Y., Bao B., Kong D., Schobert R., Padhye S.B., Sarkar F.H. Deregulation of PI3K/Akt/mTOR signaling pathways by isoflavones and its implication in cancer treatment. Anticancer Agents in Medical Chemistry 2012, [Epub ahead of print].
2. Al Zaid Siddiquee K., Turkson J. STAT3 as a target for inducing apoptosis in solid and hematological tumors. Cell Research 2008, 18:254-267.
3. Banerjee S., Kaseb A.O., Wang Z., Kong D., Mohammad M., Padhye S., Sarkar F.H., Mohammad R.M. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Research 2009, 69:5575-5583.
4. Bardeesy N., DePinho R.A. Pancreatic cancer biology and genetics. Nature Reviews Cancer 2002, 2:897-909.
5. Burris H.A., Moore M.J., Andersen J., Green M.R., Rothenberg M.L., Modiano M.R., Cripps M.C., Portenoy R.K., Storniolo A.M., Tarassoff P., Nelson R., Dorr F.A., Stephens C.D., Von Hoff D.D. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. Journal of Clinical Oncology 1997, 15:2403-2413.
6. Chun J.Y., Tummala R., Nadiminty N., Lou W., Liu C., Yang J., Evans C.P., Zhou Q., Gao A.C. Andrographolide, an herbal medicine, inhibits interleukin-6 expression and suppresses prostate cancer cell growth. Genes Cancer 2010, 1:868-876.
7. Corcoran R.B., Contino G., Deshpande V., Tzatsos A., Conrad C., Benes C.H., Levy D.E., Settleman J., Engelman J.A., Bardeesy N. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Research 2011, 71:5020-5029.
8. Darnell J.E. STATs and gene regulation. Science 1997, 277:1630-1635.
9. Dey S.K., Bose D., Hazra A., Naskar S., Nandy A., Munda R.N., Das S., Chatterjee N., Mondal N.B., Banerjee S., Saha K.D. Cytotoxic Activity and Apoptosis-Inducing Potential of Di-spiropyrrolidino and Di-spiropyrrolizidino Oxindole Andrographolide Derivatives. PLoS One 2013, 8:e58055.
10. Frame M.C. Src in cancer: deregulation and consequences for cell behaviour. Biochimica et Biophysica Acta 2002, 1602:114-130.
11. Gordaliza M. Natural products as leads to anticancer drugs. Clinical and Translational Oncology 2007, 9:767-776.
12. Gunn E.J., Williams J.T., Huynh D.T., Iannotti M.J., Han C., Barrios F.J., Kendall S., Glackin C.A., Colby D.A., Kirshner J. The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma. Leukemia and Lymphoma 2011, 52:1085-1097.
13. Iruretagoyena M.I., Tobar J.A., Gonzalez P.A., Sepulveda S.E., Figueroa C.A., Burgos R.A., Hancke J.L., Kalergis A.M. Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. Journal of Pharmacology and Experimental Therapeutics 2005, 312:366-372.
14. Jada S.R., Matthews C., Saad M.S., Hamzah A.S., Lajis N.H., Stevens M.F., Stanslas J. Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G(1) arrest and apoptosis. British Journal of Pharmacology 2008, 155:641-654.
15. Jamieson N.B., Carter C.R., McKay C.J., Oien K.A. Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. Clinical Cancer Research 2011, 17:3316-3331.
16. Ji L., Shen K., Jiang P., Morahan G., Wang Z. Critical roles of cellular glutathione homeostasis and jnk activation in andrographolide-mediated apoptotic cell death in human hepatoma cells. Molecular Carcinogenesis 2011, 50:580-591.
17. Jiang C.G., Li J.B., Liu F.R., Wu T., Yu M., Xu H.M. Andrographolide inhibits the adhesion of gastric cancer cells to endothelial cells by blocking E-selectin expression. Anticancer Research 2007, 27:2439-2447.
18. Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y., Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008, 321:1801-1806.
19. Kagawa S., Takano S., Yoshitomi H., Kimura F., Satoh M., Shimizu H., Yoshidome H., Ohtsuka M., Kato A., Furukawa K., Matsushita K., Nomura F., Miyazaki M. Akt/mTOR signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic cancer cells. Journal of Surgical Research 2012, 178:758-767.
20. Kumar S., Patil H.S., Sharma P., Kumar D., Dasari S., Puranik V.G., Thulasiram H.V., Kundu G.C. Andrographolide inhibits osteopontin expression and breast tumor growth through down regulation of PI3 kinase/Akt signaling pathway. Current Molecular Medicine 2012, 12:952-966.
21. Lee M.A., Park G.S., Lee H.J., Jung J.H., Kang J.H., Hong Y.S., Lee K.S., Kim D.G., Kim S.N. Survivin expression and its clinical significance in pancreatic cancer. BMC Cancer 2005, 5:127.
22. Lee Y.C., Lin H.H., Hsu C.H., Wang C.J., Chiang T.A., Chen J.H. Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway. European Journal of Pharmacology 2010, 632:23-32.
23. Li J., Cheung H.Y., Zhang Z., Chan G.K., Fong W.F. Andrographolide induces cell cycle arrest at G2/M phase and cell death in HepG2 cells via alteration of reactive oxygen species. European Journal of Pharmacology 2007, 568:31-44.
24. Li Y., Zhang P., Qiu F., Chen L., Miao C., Li J., Xiao W., Ma E. Inactivation of PI3K/Akt signaling mediates proliferation inhibition and G2/M phase arrest induced by andrographolide in human glioblastoma cells. Life Science 2012, 90:962-967.
25. Lim J.C., Chan T.K., Ng D.S., Sagineedu S.R., Stanslas J., Wong W.S. Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. Clinical and Experimental Pharmacology and Physiology 2012, 39:300-310.
26. Lin H.H., Tsai C.W., Chou F.P., Wang C.J., Hsuan S.W., Wang C.K., Chen J.H. Andrographolide down-regulates hypoxia-inducible factor-1alpha in human non-small cell lung cancer A549 cells. Toxicology and Applied Pharmacology 2011, 250:336-345.
27. Lin L., Hutzen B., Zuo M., Ball S., Deangelis S., Foust E., Pandit B., Ihnat M.A., Shenoy S.S., Kulp S., Li P.K., Li C., Fuchs J., Lin J. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Research 2010, 70:2445-2454.
28. Mann J. Natural products in cancer chemotherapy: past, present and future. Nature Reviews Cancer 2002, 2:143-148.
29. Moore M.J., Goldstein D., Hamm J., Figer A., Hecht J.R., Gallinger S., Au H.J., Murawa P., Walde D., Wolff R.A., Campos D., Lim R., Ding K., Clark G., Voskoglou-Nomikos T., Ptasynski M., Parulekar W. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology 2007, 25:1960-1966.
30. Nagaraj N.S., Washington M.K., Merchant N.B. Combined blockade of Src kinase and epidermal growth factor receptor with gemcitabine overcomes STAT3-mediated resistance of inhibition of pancreatic tumor growth. Clinical Cancer Research 2011, 17:483-493.
31. Nicholson K.M., Anderson N.G. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 2002, 14:381-395.
32. Oshima M., Okano K., Muraki S., Haba R., Maeba T., Suzuki Y., Yachida S. Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer. Annals of Surgery 2013, 258:336-346.
33. Scholz A., Heinze S., Detjen K.M., Peters M., Welzel M., Hauff P., Schirner M., Wiedenmann B., Rosewicz S. Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology 2003, 125:891-905.
34. Sheeja K., Guruvayoorappan C., Kuttan G. Antiangiogenic activity of Andrographis paniculata extract and andrographolide. International Immunopharmacology 2007, 7:211-221.
35. Sheeja K., Kuttan G. Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide. Immunopharmacology and Immunotoxicology 2007, 29:81-93.
36. Shen Y.C., Chen C.F., Chiou W.F. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. British Journal of Pharmacology 2002, 135:399-406.
37. Shi M.D., Lin H.H., Chiang T.A., Tsai L.Y., Tsai S.M., Lee Y.C., Chen J.H. Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down-regulation of MMP-7 expression. Chemico Biological Interactions 2009, 180:344-352.
38. Shi M.D., Lin H.H., Lee Y.C., Chao J.K., Lin R.A., Chen J.H. Inhibition of cell-cycle progression in human colorectal carcinoma Lovo cells by andrographolide. Chemico Biological Interactions 2008, 174:201-210.
39. Siegel R., Naishadham D., Jemal A. Cancer statistics, 2012. CA: A Cancer Journal of Clinicians 2012, 62:10-29.
40. Simon P.O., McDunn J.E., Kashiwagi H., Chang K., Goedegebuure P.S., Hotchkiss R.S., Hawkins W.G. Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the treatment of human pancreatic adenocarcinoma. International Journal of Cancer 2009, 125:942-951.
41. Sun J., Blaskovich M.A., Jove R., Livingston S.K., Coppola D., Sebti S.M. Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity. Oncogene 2005, 24:3236-3245.
42. Tamm I., Kornblau S.M., Segall H., Krajewski S., Welsh K., Kitada S., Scudiero D.A., Tudor G., Qui Y.H., Monks A., Andreeff M., Reed J.C. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clinical Cancer Research 2000, 6:1796-1803.
43. Tan Y., Chiow K.H., Huang D., Wong S.H. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells. British Journal of Pharmacology 2010, 159:1497-1510.
44. Thoennissen N.H., Iwanski G.B., Doan N.B., Okamoto R., Lin P., Abbassi S., Song J.H., Yin D., Toh M., Xie W.D., Said J.W., Koeffler H.P. Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells. Cancer Research 2009, 69:5876-5884.
45. Trivedi N.P., Rawal U.M., Patel B.P. Hepatoprotective effect of andrographolide against hexachlorocyclohexane-induced oxidative injury. Integrative Cancer Therapies 2007, 6:271-280.
46. Vincent A., Herman J., Schulick R., Hruban R.H., Goggins M. Pancreatic cancer. Lancet 2011, 378:607-620.
47. Wang S.J., Gao Y., Chen H., Kong R., Jiang H.C., Pan S.H., Xue D.B., Bai X.W., Sun B. Dihydroartemisinin inactivates NF-kappaB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo. Cancer Letters 2010, 293:99-108.
48. Wang Y.W., Wang S.J., Zhou Y.N., Pan S.H., Sun B. Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-kappaB and nuclear factor-kappaB-regulated gene products in pancreatic cancer both in vitro and in vivo. Journal of Cancer Research and Clinical Oncology 2012, 138:785-797.
49. Warfel N.A., El-Deiry W.S. p21WAF1 and tumourigenesis: 20 years after. Current Opinion in Oncology 2013, 25:52-58.
50. Yang L., Wu D., Luo K., Wu S., Wu P. Andrographolide enhances 5-fluorouracil-induced apoptosis via caspase-8-dependent mitochondrial pathway involving p53 participation in hepatocellular carcinoma (SMMC-7721) cells. Cancer Letters 2009, 276:180-188.
51. Yang S., Evens A.M., Prachand S., Singh A.T., Bhalla S., David K., Gordon L.I. Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone andrographolide, the active component of Andrographis paniculata. Clinical Cancer Research 2010, 16:4755-4768.
52. Zeng Y.X., el-Deiry W.S. Regulation of p21WAF1/CIP1 expression by p53-independent pathways. Oncogene 1996, 12:1557-1564.
53. Zhou J., Ong C.N., Hur G.M., Shen H.M. Inhibition of the JAK-STAT3 pathway by andrographolide enhances chemosensitivity of cancer cells to doxorubicin. Biochemical Pharmacology 2010, 79:1242-1250.
54. Zhou J., Zhang S., Ong C.N., Shen H.M. Critical role of pro-apoptotic Bcl-2 family members in andrographolide-induced apoptosis in human cancer cells. Biochemical Pharmacology 2006, 72:132-144.