e13514 Background: Brazilin [7, 11b-dihydrobenz(b)indeno[1,2-d]pyran-3, 6a, 9, 10(6H)-tetrol] isolated from Caesalpinia sappan has been showed various biological activities such as anti-inflammationy, anti-bacteria and anti-platelet aggregation. However, there is no report on its anti-cancer activity. Methods: In the present study, the anti-cancer mechanism of brazilin was investigated on apoptosis and cell cycle arrest in human multiple myeloma U266 cells. Results: Brazilin significantly increased sub-G1 population and TUNEL-positive cells undergoing apoptosis. Also, brazilin activated caspase-3 and regulated the expression of Bcl-2 family proteins including Bax, Bcl-xL and Bcl-2, via mitochondria-dependent pathway. Futhermore, cell cycle analysis revealed that brazilin induced G2/M arrest of cell cycle along with apoptosis induction in U266 cells. Consistently, brazilin elevated the expression of cyclin-dependent kinase (CDK) inhibitor proteins p21 and p27 and activated G2 checkpoint-related proteins such as Chk1, Chk2 and γ-H2Ax. Of note, brazilin significantly inhibited the activity of histone deacetylases (HDACs), transcription factors involved in the regulation of apoptosis and cell cycle arrest and the expression of HDAC-1 and -2 at both protein and mRNA levels. Notably, brazilin significantly potentiated the cytotoxic effect of chemotherapeutic agents such as bortezomib or doxorubicin in U266 cells. Conclusions: Taken together, our findings suggest that brazilin has a chemotherapeutic potential, via HDAC-mediated apoptosis and G2/M arrest for multiple myeloma treatment.
A natural peptide, dolastatin 15, induces G2/M cell cycle arrest and apoptosis of human multiple myeloma cells
