Positive Health Online

Abstract

LIU and COLLEAGUES, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China investigated the antitumor effects of DCHA-HF - a constituent isolated from the extract of the flowering upper portion of the plant Hypericum perforatum - on the chronic myeloid leukemia K562 cell line.

Background

Hyperforin is an abundant phloroglucinol-type constituent isolated from the extract of the flowering upper portion of the plant Hypericum perforatum L. The dicyclohexylammonium salt of hyperforin (DCHA-HF) has exhibited antitumor and antiangiogenic activities in various cancer cells.

Methodology

Here, the antitumor effects of DCHA-HF on the chronic myeloid leukemia K562 cell line were investigated for the first time.

Results

DCHA-HF exhibited dose- and time-dependent inhibitory activities against K562 cells, with IC(50) values of 8.6 and 3.2 muM for 48 h and 72 h of treatment, respectively, which was more effective than that of the hyperforin. In contrast, little cytotoxic activity was observed with DCHA-HF on HUVECs. DCHA-HF treatment resulted in induction of apoptosis as evidenced from DNA fragmentation, nuclear condensation and increase of early apoptotic cells by DAPI staining analysis, TUNEL assay and Annexin V-FITC/PI double-labelled staining analysis, respectively. Moreover, DCHA-HF elicited dissipation of mitochondrial trans-membrane potential that commenced with the release of cytochrome c through down-regulation of expression of anti-apoptotic proteins and up-regulation of expression of pro-apoptotic proteins. DCHA-HF treatment induced activation of the caspase 3, 8, and 9 cascade and subsequent PARP cleavage, and DCHA-HF-induced apoptosis was significantly inhibited by caspase inhibitors. Treated cells were arrested at the G1 phase of the cell cycle and the expression of p53 and p27(Kip1), two key regulators related to cell cycle and apoptosis, was up-regulated.

Conclusion

These results suggest that DCHA-HF inhibits K562 cell growth by inducing caspase-dependent apoptosis mediated by a mitochondrial pathway and arresting the cell cycle at the G1 phase. Therefore, DCHA-HF is a potential chemotherapeutic antitumor drug for chronic myeloid leukemia therapy.

References

Liu JY, Liu Z, Wang DM, Li MM, Wang SX, Wang R, Chen JP, Wang YF and Yang DP. Induction of apoptosis in K562 cells by dicyclohexylammonium salt of hyperforin through a mitochondrial-related pathway. Source Chemico-Biological Interactions. 190(2-3):91-101, Apr 25 2011.

Comment

The above research emanating from China demonstrates the progress in understanding at the molecular level how this extract- DCHA-HF - from Hypericum perforatum L induces caspase-dependent apoptosis in the chronic myeloid leukemia K562 cell line via a mitochondrial mechanism, making DCHA-HF a potential chemotherapeutic antitumour drug for chronic myeloid leukemia.