Two Novel Curcumin Analogues Induced Reactive Oxygen Species Generation and Mitochondrial-Related Apoptosis in Human Breast Cancer MCF - 7 Cells
- *Corresponding Author:
- Qingyong Li
332# No. 26 Hexing Road
Harbin City 150040
Heilongjiang Province, China
E-mail: [email protected]
Received date: February 17, 2016 Accepted date: March 04, 2016 Published date: March 10, 2016
Citation: Luo S, Li Q, Chen J, Wang W (2016) Two Novel Curcumin Analogues Induced Reactive Oxygen Species Generation and Mitochondrial-Related Apoptosis in Human Breast Cancer MCF - 7 Cells. J App Pharm 8:215. doi: 10.4172/1920-4159.1000215
Copyright: © 2016 Luo S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Curcumin has been shown to have significant protective effects against cancer and induction of apoptosis is a crucial strategy for cancer therapy, so we have now evaluated the mechanisms involved in two novel asymmetric curcumin analogues induced cell death in MCF - 7 cells.
Methods: The cytotoxicity of two curcumin analogues towards tumor cells was investigated by MTT assays. The morphological analysis using a laser scanning confocal microscope. Futher cell cycle analysis, reactive oxygen species (ROS), mitochondrial transmembrane potentials (Δφm), intracellular Ca2+ levels analysis and apoptosis assays via a flow cytometry (FCM). We used western blot assays to determine the expressions of apoptosis-related factors and p38MAPK at protein level.
Results: MCF - 7 cells showed a significant loss of viability, reduced mitochondrial membrane potential (Δφm), increased intracellular Ca2+ levels, and increased production of ROS, which activated the pro-apoptotic p38 mitogen-activated protein kinase. Pretreatment with the antioxidant, N-acetylcysteine, inhibited both two curcumin analogues mediated ROS production and cytotoxicity. Western blotting revealed that the loss of Δφm inhibited Bcl-2, and induced Bax and Bak expression; this promoted release of cytochrome c and apoptosis inducing factor from the mitochondria to the cytosol, activation of caspase-9 and caspase-3 in the cytosol, and induction of apoptosis.
Conclusion: The two curcumin analogues displays strong antitumor effect through ROS-dependent mitochondria apoptosis pathway in MCF - 7 cells, and has promising potential to be developed as antitumor compounds.