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Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity.
Acta Pharmacol Sin. 2006 Nov; 27(11):1447-52.AP

Abstract

AIM

To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved.

METHODS

The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-x(L), XIAP and Bax protein were detected using Western blotting analysis.

RESULTS

Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-x(L) and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64+/-8 micromol/L, 93+/-11 micromol/L, and 153+/-11 micromol/L, respectively. Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity.

CONCLUSION

Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.

Authors+Show Affiliations

Institute of Hematology, Union Hospital, Tongji medical college, Huazhong University of Science and Technology, Wuhan 430022, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17049120

Citation

Sun, Chun-yan, et al. "Resveratrol as a Novel Agent for Treatment of Multiple Myeloma With Matrix Metalloproteinase Inhibitory Activity." Acta Pharmacologica Sinica, vol. 27, no. 11, 2006, pp. 1447-52.
Sun CY, Hu Y, Guo T, et al. Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity. Acta Pharmacol Sin. 2006;27(11):1447-52.
Sun, C. Y., Hu, Y., Guo, T., Wang, H. F., Zhang, X. P., He, W. J., & Tan, H. (2006). Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity. Acta Pharmacologica Sinica, 27(11), 1447-52.
Sun CY, et al. Resveratrol as a Novel Agent for Treatment of Multiple Myeloma With Matrix Metalloproteinase Inhibitory Activity. Acta Pharmacol Sin. 2006;27(11):1447-52. PubMed PMID: 17049120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity. AU - Sun,Chun-yan, AU - Hu,Yu, AU - Guo,Tao, AU - Wang,Hua-fang, AU - Zhang,Xiao-ping, AU - He,Wen-juan, AU - Tan,Hao, PY - 2006/10/20/pubmed PY - 2007/12/12/medline PY - 2006/10/20/entrez SP - 1447 EP - 52 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 27 IS - 11 N2 - AIM: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. METHODS: The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-x(L), XIAP and Bax protein were detected using Western blotting analysis. RESULTS: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-x(L) and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64+/-8 micromol/L, 93+/-11 micromol/L, and 153+/-11 micromol/L, respectively. Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity. CONCLUSION: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9. SN - 1671-4083 UR - https://www.unboundmedicine.com/medline/citation/17049120/Resveratrol_as_a_novel_agent_for_treatment_of_multiple_myeloma_with_matrix_metalloproteinase_inhibitory_activity_ L2 - https://doi.org/10.1111/j.1745-7254.2006.00343.x DB - PRIME DP - Unbound Medicine ER -