Biomol Ther.  2014 Nov;22(6):519-524. 10.4062/biomolther.2014.112.

Role of Annexin A5 on Mitochondria-Dependent Apoptosis Induced by Tetramethoxystilbene in Human Breast Cancer Cells

• Hong M
• Park N
• Chun YJ

• KMID: 2170593
• DOI: http://doi.org/10.4062/biomolther.2014.112

Abstract

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a trans-stilbene analogue, induces apoptosis in human cancer cells. However, the detailed mechanisms of mitochondria-dependent apoptosis induced by TMS are not fully understood. In the present study, the possible roles of annexin A5 in TMS-mediated apoptosis were investigated in MCF7 human breast cancer cells. Quantitative real-time PCR analysis and Western blot analysis showed that the expression of annexin A5 was strongly increased in TMS-treated cells. TMS caused a strong translocation of annexin A5 from cytosol into mitochondria. Confocal laser scanning microscopic analysis clearly showed that TMS induced translocation of annexin A5 into mitochondria. TMS increased the expression and oligomerization of voltage-dependent anion channel (VDAC) 1, which may promote mitochondria-dependent apoptosis through disruption of mitochondrial membrane potential. When cells were treated with TMS, the levels of Bax, and Bak as well as annexin A5 were strongly enhanced. Moreover, we found that the cytosolic release of apoptogenic factors such as cytochrome c, or apoptosis-inducing factor (AIF) in mitochondria was markedly increased. Annexin A5 depletion by siRNA led to decreased proapoptotic factors such as Bax , Bak, and annexin A5. Taken together, our results indicate that annexin A5 may play an important role in TMS-mediated mitochondrial apoptosis through the regulation of proapoptotic proteins and VDAC1 expression.

Keyword

Tetramethoxystilbene; Annexin A5; VDAC1; Bax

MeSH Terms

Annexin A5*
Apoptosis Inducing Factor
Apoptosis*
Blotting, Western
Breast Neoplasms*
Cytochromes c
Cytosol
Humans
Membrane Potential, Mitochondrial
Mitochondria
Real-Time Polymerase Chain Reaction
RNA, Small Interfering
Annexin A5
Apoptosis Inducing Factor
Cytochromes c
RNA, Small Interfering