Lucidenic acid B induces apoptosis in human leukemia cells via a mitochondria-mediated pathway.
Ganoderma lucidum is known as a medicinal mushroom used in traditional Chinese medicine. In the present study, the effect of lucidenic acids (A, B, C, and N) isolated from a new G. lucidum (YK-02) on induction of cell apoptosis and the apoptotic pathway in HL-60 cells were investigated. The results demonstrated that lucidenic acids decreased cell population growth of HL-60 cells, assessed with the MTT assay. The cell cycle assay indicated that treatment of HL-60 cells with lucidenic acid A, C, and N caused cell cycle arrest in the G 1 phase. Lucidenic acid B (LAB) did not affect the cell cycle profile; however, it increased the number of early and late apoptotic cells but not necrotic cells. Treatment of HL-60 cells with LAB caused loss of mitochondria membrane potential. Moreover, the ratio of expression levels of pro- and antiapoptotic Bcl-2 family members was changed by LAB treatment. LAB-induced apoptosis involved release of mitochondria cytochrome c and subsequently induced the activation of caspase-9 and caspase-3, which were followed by cleavage of poly(ADP-ribose) polymerase (PARP). Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented LAB from inhibiting cell viability in HL-60 cells. Our finding may be critical to the chemopreventive potential of lucidenic acid B.
Hsu
Chin-Lin
CL
Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
Yu
Yu-Shan
YS
Yen
Gow-Chin
GC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002793:Cholic Acids / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure
D000970:Antineoplastic Agents; D002793:Cholic Acids; C527145:lucidenic acid B