Gossypol induces apoptosis in multiple myeloma cells by inhibition of interleukin-6 signaling and Bcl-2/Mcl-1 pathway

International Journal of Oncology

Volumn 45, Issue 6, 2014, Pages 2278-2286

  Sadahira, Ken ^a   Sagawa, Morihiko ^b   Nakazato, Tomonori ^c   Uchida, Hideo ^d   Ikeda, Yasuo ^a   Okamoto, Shinichiro ^a   Nakajima, Hideaki ^a   Kizaki, Masahiro ^b  

^a KEIO UNIVERSITY   (Japan)

^b SAITAMA MEDICAL UNIVERSITY   (Japan)

^c Yokohama Municipal Hospital   (Japan)

^d TOKYO ELECTRIC POWER COMPANY   (Japan)

Author keywords

Apoptosis; Bcl 2; Gossypol; Interleukin 6; Multiple myeloma

Indexed keywords

GOSSYPOL; INTERLEUKIN 6; MCL1 PROTEIN, HUMAN; PROTEIN BCL 2; PROTEIN MCL 1;

APOPTOSIS; BIOSYNTHESIS; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HUMAN; MULTIPLE MYELOMA; PATHOLOGY; PHOSPHORYLATION; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

APOPTOSIS; CELL LINE, TUMOR; GENE EXPRESSION REGULATION, NEOPLASTIC; GOSSYPOL; HUMANS; INTERLEUKIN-6; MULTIPLE MYELOMA; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-BCL-2; SIGNAL TRANSDUCTION;

EID: 84907684898     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2014.2652     Document Type: Article

References (43)

1. Hideshima T and Anderson KC: Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Cancer 2:927-937, 2002.
2. Hideshima T, Bergsagel PL, Kuehl WM and Anderson KC: Advances in biology of multiple myeloma: clinical applications. Blood 104:607-618, 2004.
3. Pettersson M, Jernberg-Wiklund H, Larsson LG, et al: Expression of the bcl-2 gene in human multiple myeloma cell lines and normal plasma cells. Blood 79:495-502, 1992.
4. Oancea M, Mani A, Hussein MA and Almasan A: Apoptosis of multiple myeloma. Int J Hematol 80:224-231, 2004.
5. van de Donk NW, Bloem AC, van der Spek E and Lokhorst HM: New treatment strategies for multiple myeloma by targeting BCL-2 and the mevalonate pathway. Curr Pharm Des 12:327-340, 2006.
6. Guo S, Zhi Y, Yang H, et al: Bcl-2 expression is associated with poor prognosis of solitary plasmacytoma of bone. Ann Hematol 93:471-477, 2013.
7. Kridel R, Sehn LH and Gascoyne RD: Pathogenesis of follicular lymphoma. J Clin Invest 122:3424-3431, 2012.
8. Bende RJ, Smit LA and van Noesel CJ: Molecular pathways in follicular lymphoma. Leukemia 21:18-29, 2007.
9. Weyhenmeyer B, Murphy AC, Prehn JH and Murphy BM: Targeting the anti-apoptotic Bcl-2 family members for the treatment of cancer. Exp Oncol 34:192-199, 2012.
10. Juin P, Geneste O, Gautier F, Depil S and Campone M: Decoding and unlocking the BCL-2 dependency of cancer cells. Nat Rev Cancer 13:455-465, 2013.
11. Shamas-Din A, Kale J, Leber B and Andrews DW: Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol 5: a008714, 2013.
12. Ola MS, Nawaz M and Ahsan H: Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 351:41-58, 2011.
13. Tsujimoto Y: Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol 195:158-167, 2003.
14. Kang MH and Reynolds CP: Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res 15:1126-1132, 2009.
15. Keshmiri-Neghab H and Goliaei B: Therapeutic potential of gossypol: an overview. Pharm Biol 52:124-128, 2014.
16. Wang X, Howell CP, Chen F, Yin J and Jiang Y: Gossypol - a polyphenolic compound from cotton plant. Adv Food Nutr Res 58:215-263, 2009.
17. Lopez LM, Grimes DA and Schulz KF: Nonhormonal drugs for contraception in men: a systematic review. Obstet Gynecol Surv 60:746-752, 2005.
18. Oliver CL, Bauer JA, Wolter KG, et al: In vitro effects of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res 10:7757-7763, 2004.
19. Stein RC, Joseph AE, Matlin SA, Cunningham DC, Ford HT and Coombes RC: A preliminary clinical study of gossypol in advanced human cancer. Cancer Chemother Pharmacol 30:480-482, 1992.
20. Le Blanc M, Russo J, Kudelka AP and Smith JA: An in vitro study of inhibitory activity of gossypol, a cottonseed extract, in human carcinoma cell lines. Pharmacol Res 46:551-555, 2002.
21. Kapoor S: Attenuating effect of gossypol on tumor growth in systemic malignancies. Cell Biochem Biophys 67:1551-1552, 2013.
22. Xu P, Ye W, Jen R, Lin SH, Kuo CT and Lin YC: Mitogenic activity of zeranol in human breast cancer cells is enhanced by leptin and suppressed by gossypol. Anticancer Res 29:4621-4628, 2009.
23. Anderson MA, Huang DC and Roberts AW: BH3 mimetic therapy: an emerging and promising approach to treating chronic lymphocytic leukemia. Leuk Lymphoma 54:909-911, 2013.
24. Voss V, Senft C, Lang V, et al: The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma. Mol Cancer Res 8:1002-1016, 2010.
25. Meng Y, Tang W, Dai Y, et al: Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa. Mol Cancer Ther 7:2192-2202, 2008.
26. Volate SR, Kawasaki BT, Hurt EM, et al: Gossypol induces apoptosis by activating p53 in prostate cancer cells and prostate tumor-initiating cells. Mol Cancer Ther 9:461-470, 2010.
27. Huang LH, Hu JQ, Tao WQ, et al: Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells. Eur J Pharmacol 645:9-13, 2010.
28. Czabotar PE, Lessene G, Strasser A and Adams JM: Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 15:49-63, 2013.
29. Ruvolo PP, Deng X and May WS: Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia 15:515-522, 2001.
30. Deng X, Kornblau SM, Ruvolo PP and May WS Jr: Regulation of Bcl2 phosphorylation and potential significance for leukemic cell chemoresistance. J Natl Cancer Inst Monogr pp30-37, 2001.
31. Tamura Y, Simizu S and Osada H: The phosphorylation status and anti-apoptotic activity of Bcl-2 are regulated by ERK and protein phosphatase 2A on the mitochondria. FEBS Lett 569:249-255, 2004.
32. Sahin F, Avci CB, Gunduz C, Sezgin C, Simsir IY and Saydam G: Gossypol exerts its cytotoxic effect on HL-60 leukemic cell line via decreasing activity of protein phosphatase 2A and interacting with human telomerase reverse transcriptase activity. Hematology 15:144-150, 2010.
33. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G and Schaper F: Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1-20, 2003.
34. Catlett-Falcone R, Landowski TH, Oshiro MM, et al: Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 10:105-115, 1999.
35. Subramanian M and Shaha C: Up-regulation of Bcl-2 through ERK phosphorylation is associated with human macrophage survival in an estrogen microenvironment. J Immunol 179:2330-2338, 2007.
36. Puthier D, Bataille R and Amiot M: IL-6 up-regulates Mcl-1 in human myeloma cells through JAK/STAT rather than ras/MAP kinase pathway. Eur J Immunol 29:3945-3950, 1999.
37. Puthier D, Derenne S, Barille S, et al: Mcl-1 and Bcl-xL are co-regulated by IL-6 in human myeloma cells. Br J Haematol 107:392-395, 1999.
38. Wuilleme-Toumi S, Robillard N, Gomez P, et al: Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival. Leukemia 19:1248-1252, 2005.
39. Zhang B, Gojo I and Fenton RG: Myeloid cell factor-1 is a critical survival factor for multiple myeloma. Blood 99:1885-1893, 2002.
40. Derenne S, Monia B, Dean NM, et al: Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x (L) is an essential survival protein of human myeloma cells. Blood 100:194-199, 2002.
41. Ihle JN, Thierfelder W, Teglund S, et al: Signaling by the cytokine receptor superfamily. Ann NY Acad Sci 865:1-9, 1998.
42. Nakashima K and Taga T: gp130 and the IL-6 family of cytokines: signaling mechanisms and thrombopoietic activities. Semin Hematol 35:210-221, 1998.
43. Lin J, Wu Y, Yang D and Zhao Y: Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncol Rep 30:731-738, 2013.