Jia Q.,The Twelfth Guangzhou Peoples Hospital |
Chen L.,The Twelfth Guangzhou Peoples Hospital |
Zhan Y.,The Twelfth Guangzhou Peoples Hospital |
Feng K.,The Twelfth Guangzhou Peoples Hospital |
And 3 more authors.
Chinese Journal of Cancer Biotherapy | Year: 2014
Objective: To investigate the influence of curcumin (Cur) on the extrinsic apoptosis pathway of human multiple myeloma cell line ARH-77. Methods: ARH-77 cells were treated with Cur at 6.25, 12.5, 25, 50, 100 and 200 μmol/L. At 12, 24 and 48 h after treatment, cell viability was analyzed by MTT assay and growth inhibition was accordingly calculated. At 24 h after treatment, changes in the cell morphology were assessed by Hoechst 33258 staining, cell cycle progression and levels of Fas/Fasl and TRAIL/TRAIL-R were analyzed by flow cytometry, and the activity of caspase 8 was determined by colorimetry. Results: Cur significantly inhibited the growth of ARH-77 cells in a time- and dose-dependent manner. At 24 h after treatment, Cur induced apoptosis in ARH-77 cells in a dose-dependent manner; the percentage of apoptotic cells was (10.35±0.35)% at 6.25 μmol/L, (14.35±1.34)% at 12.5 μmol/L and (36.65±1.06)% at 25 μmol/L, significantly higher than that in untreated control cells ([3.83±0.32]%, P<0.01). Apoptotic bodies and cell cycle arrest at the G0/G1 phase were seen in ARH-77cells treated with 25 μmol/L Cur. Caspase 8 activity was significantly higher in ARH-77 cells treated with Cur at 6.26 μmol/L(0.223±0.018), 12.5 μmol/L (0.263±0.019), or 25.0 μmol/L (0.240±0.035) than in untreated control cells (0.154±0.007) (P<0.05). Compared with the non-treatment control, 24 h Cur treatment at 6.25 μmol/L significantly increased the protein levels of Fas ([99.05±0.49]% vs [92.10±0.7]%, P=0.000), FasL ([9.05±0.78]% vs [1.73±1.19]%, P=0.008), TRAIL ([1.35±0.07]% vs [0.55±0.07]%, P=0.008), DR4, DcR1 and DcR2 but significantly decreased DR5 ([0.95±0.07]% vs [7.70±0.29]%, P=0.001). The effect of Cur on DcR1 ([4.35±1.20]% vs [14.25±0.21]%, P=0.008) and DcR2 ([0.75±0.21]% vs [1.65±0.71]%, P=0.03) were more pronounced at 25.0 μmol/L than at 12.5 μmol/L. Conclusion: Cur is able to inhibit the growth of ARH-77 cells through activating the extrinsic apoptosis pathway and thereby may offer a potential therapeutic agent for multiple myeloma. Source