A preliminary study of the effect of curcumin on the expression of p53 protein in a human multiple myeloma cell line

Li,Wei; Wang,Yaomei; Song,Yongping; Xu,Linping; Zhao,Junmei; Fang,Baijun

doi:10.3892/ol.2015.2946

A preliminary study of the effect of curcumin on the expression of p53 protein in a human multiple myeloma cell line

Authors:
- Wei Li
- Yaomei Wang
- Yongping Song
- Linping Xu
- Junmei Zhao
- Baijun Fang
View Affiliations

Affiliations: Department of Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China , School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, P.R. China, Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
Published online on: February 9, 2015 https://doi.org/10.3892/ol.2015.2946
Pages: 1719-1724

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Curcumin is an inexpensive, natural plant ingredient with protease inhibitor effects. The present study aimed to analyze the inhibitory effects of curcumin on the multiple myeloma (MM) RPMI 8226 cell line, and examine the underlying mechanism that promotes the apoptosis of RPMI 8226 cells. A growth curve was constructed in order to observe the relative growth velocity, and MTT was used to analyze the effect of different concentrations of curcumin on inhibiting the proliferation of the RPMI 8226 cells. The mRNA expression of the p53, Bax and MDM2 genes was detected using quantitative polymerase chain reaction. The expression of p53 protein in the MM RPMI 8226 cells following treatment with curcumin was detected by western blotting and ELISA. Curcumin inhibited the proliferation of the MM RPMI 8226 cells in a dose‑ and time‑dependent manner. In the MM RPMI 8226 cells treated with curcumin, the expression of the p53 and Bax genes was upregulated, while the expression of the MDM2 gene was downregulated. p53 protein expression was higher in the curcumin experimental group compared with the control group. Subsequent to treatment with curcumin, the growth of the MM RPMI 8226 cell line was inhibited in a concentration‑ and time‑dependent manner. In the MM RPMI 8226 cells treated with curcumin, p53 protein levels were upregulated, which suggested that curcumin may promote the apoptosis of MM cells by upregulating p53 protein expression.

View Figures

View References

1	Raab MS, Podar K, Breitkreutz I, et al: Multiple myeloma. Lancet. 374:324–339. 2009. View Article : Google Scholar : PubMed/NCBI
2	Garcia-Sanz R, Mateos MV and San Miguel J: Multiple myeloma. Med Clin (Barc). 129:104–115. 2007.(In Spanish). View Article : Google Scholar
3	Krstevska SB, Sotirova T, Balkanov T and Genadieva-Stavric S: Treatment approach of nontransplant patients with multiple myeloma. Mater Sociomed. 26:348–351. 2014. View Article : Google Scholar
4	Jakob C, Egerer K, Liebisch P, et al: Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma. Blood. 109:2100–2105. 2007. View Article : Google Scholar
5	Adams J and Kauffman M: Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest. 22:304–311. 2004. View Article : Google Scholar : PubMed/NCBI
6	Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP and Dou QP: Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res. 68:7283–7292. 2008. View Article : Google Scholar : PubMed/NCBI
7	Dhillon N, Aggarwal BB, Newman RA, et al: Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 14:4491–4499. 2008. View Article : Google Scholar : PubMed/NCBI
8	Garcea G, Jones DJ, Singh R, et al: Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer. 90:1011–1015. 2004. View Article : Google Scholar : PubMed/NCBI
9	von Metzler I, Krebbel H, Kuckelkorn U, et al: Curcumin diminishes human osteoclastogenesis by inhibition of the signalosome-associated I kappaB kinase. J Cancer Res Clin Oncol. 135:173–179. 2009. View Article : Google Scholar
10	Kunnumakkara AB, Anand P and Aggarwal BB: Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 269:199–225. 2008. View Article : Google Scholar : PubMed/NCBI
11	Kudo C, Yamakoshi H, Sato A, et al: Novel curcumin analogs, GO-Y030 and GO-Y078, are multi-targeted agents with enhanced abilities for multiple myeloma. Anticancer Res. 31:3719–3726. 2011.PubMed/NCBI
12	Li B and Dou QP: Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci USA. 97:3850–3855. 2000. View Article : Google Scholar : PubMed/NCBI
13	Scheffner M, Werness BA, Huibregtse JM, Levine AJ and Howley PM: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 63:1129–1136. 1990. View Article : Google Scholar : PubMed/NCBI
14	Chng WJ, Price-Troska T, Gonzalez-Paz N, et al: Clinical significance of TP53 mutation in myeloma. Leukemia. 21:582–584. 2007. View Article : Google Scholar : PubMed/NCBI
15	Chang H, Qi C, Yi QL, Reece D and Stewart AK: p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood. 105:358–360. 2005. View Article : Google Scholar
16	Avet-Loiseau H, Li JY, Godon C, et al: P53 deletion is not a frequent event in multiple myeloma. Brit J Haematol. 106:717–719. 1999. View Article : Google Scholar
17	Saha MN, Micallef J, Qiu L and Chang H: Pharmacological activation of the p53 pathway in haematological malignancies. J Clin Pathol. 63:204–209. 2010. View Article : Google Scholar
18	Saha MN, Jiang H, Jayakar J, Reece D, Branch DR and Chang H: MDM2 antagonist nutlin plus proteasome inhibitor velcade combination displays a synergistic anti-myeloma activity. Cancer Biol Ther. 9:936–944. 2010. View Article : Google Scholar : PubMed/NCBI
19	Vassilev LT: MDM2 inhibitors for cancer therapy. Trends Mol Med. 13:23–31. 2007. View Article : Google Scholar
20	Shangary S and Wang S: Targeting the MDM2-p53 interaction for cancer therapy. Clin Cancer Res. 14:5318–5324. 2008. View Article : Google Scholar : PubMed/NCBI
21	Song G, Mao YB, Cai QF, Yao LM, Ouyang GL and Bao SD: Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression. Braz J Med Biol Res. 38:1791–1798. 2005. View Article : Google Scholar : PubMed/NCBI
22	Barlogie B, Zangari M, Spencer T, et al: Thalidomide in the management of multiple myeloma. Semin Hematol. 38:250–259. 2001. View Article : Google Scholar : PubMed/NCBI
23	Adams J: Proteasome inhibition in cancer: development of PS-341. Semin Oncol. 28:613–619. 2001. View Article : Google Scholar : PubMed/NCBI
24	Bharti AC, Donato N, Singh S and Aggarwal BB: Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood. 101:1053–1062. 2003. View Article : Google Scholar
25	Child JA, Morgan GJ, Davies FE, et al; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 348:1875–1883. 2003. View Article : Google Scholar : PubMed/NCBI
26	Sung B, Kunnumakkara AB, Sethi G, Anand P, Guha S and Aggarwal BB: Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model. Mol Cancer Ther. 8:959–970. 2009. View Article : Google Scholar : PubMed/NCBI
27	Bharti AC, Takada Y and Aggarwal BB: Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis. J Immunol. 172:5940–5947. 2004. View Article : Google Scholar : PubMed/NCBI
28	Jana S, Paul S and Swarnakar S: Curcumin as anti-endometriotic agent: implication of MMP-3 and intrinsic apoptotic pathway. Biochem Pharmacol. 83:797–804. 2012. View Article : Google Scholar : PubMed/NCBI
29	Wang ME, Chen YC, Chen IS, Hsieh SC, Chen SS and Chiu CH: Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes. J Nutr Biochem. 23:1352–1366. 2012. View Article : Google Scholar : PubMed/NCBI