Anticancer effect of (E)-2-hydroxy-3',4,5'-trimethoxystilbene on breast cancer cells by mitochondrial depolarization.
BACKGROUND
TMS (2,3',4,5'-tetramethoxystilbene), a stilbene analog derived from rhapontigenin, was previously demonstrated to induce apoptosis in hormone-resistant breast cancer cells. Therefore, this study investigated the anticancer effect of a new stilbene analog, HTMS ((E)-2-hydroxy-3',4,5'-trimethoxystilbene), and its mechanism in various breast cancer cell lines.


METHODS
The effect of HTMS on cell proliferation of MDA-MB-231, MCF-7, and LTED cells was evaluated using MTT assays. Cell apoptosis was detected by FITC-annexin V staining and flow cytometry analysis, changes in mitochondrial potential were determined by fluorescence microscopy using TMRE staining, and the expression of cleaved PARP and release of cytochrome c were assessed by Western blot analysis.


RESULTS
HTMS significantly decreased the cell viability of various types of breast cancer cells in a dose- and time-dependent manner, characterized by G2/M arrest of the cell cycle and the induction of apoptosis. In particular, HTMS disturbed the mitochondrial membrane potential, causing a release of cytochrome c during apoptosis. Furthermore, HTMS was superior to TMS in inhibiting cancer cell growth in a pilot comparison study.


CONCLUSIONS
HTMS is an effective apoptotic agent for breast cancer cells, making it a candidate therapeutic agent for the treatment of breast cancer.
Chae
Yee Soo
YS
Department of Medical Oncology, Kyungpook National University Hospital, Daegu, South Korea.
Kim
Jong Gwang
JG
Jung
Hyun Jun
HJ
Yang
Jung Dug
JD
Jung
Jin Hyang
JH
Aiyar
Sarah E
SE
Kim
Sanghee
S
Park
Hoyong
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D065633:Cytochrome P-450 CYP1B1; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000737:chemistry; D010446:Peptide Fragments / Q000378:metabolism; D010865:Pilot Projects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
C561464:2-hydroxy-3',4,5'-trimethoxystilbene; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D010446:Peptide Fragments; D013267:Stilbenes; C110932:tetramethyl rhodamine ethyl ester; D045304:Cytochromes c; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D011065:Poly(ADP-ribose) Polymerases