Inhibitory effects of Agaricus blazei extracts on human myeloid leukemia cells.
BACKGROUND
Agaricus blazei has been used as an adjuvant in cancer chemotherapy and is found to inhibit the growth of various types of tumor cells.


OBJECTIVE
Our study has adopted a systematic and bioassay-guided approach to optimize the extraction of Agaricus blazei for anti-leukemic bioactive components. The tumor-selective growth inhibitory activity of the extracts on leukemic cell lines was evaluated in vitro and in vivo using tumor-bearing nude mice.


METHODS
Agaricus blazei extracts were prepared using different methods. MTT and tritiated thymidine incorporation assays were used to evaluate the in vitro anti-leukemic effects. The most potent extract was further investigated using NB-4 cells-bearing nude mice and mechanistic studies using DNA fragmentation assay and cell death detection ELISA.


RESULTS
The JAB80E70 extract showed the most potent tumor-selective growth inhibitory activity against human leukemia NB-4 and K-562 cells. This is the first report of anti-leukemic activity of JAB80E70 in athymic nude mice bearing NB-4 cells. Using DNA fragmentation assays and cell death detection ELISA, JAB80E70 was found to induce apoptosis in NB-4 cells. However, the polysaccharide enriched fractions failed to show significant cytotoxicity on NB-4 cells in vitro.


CONCLUSIONS
The JAB80E70 extract exhibited potent anti-leukemic effect in vitro and in vivo. The effect can be attributed, at least in part, to the induction of apoptosis. Besides, polysaccharides in Agaricus blazei may not possess direct anti-leukemic activity in vitro.
Kim
Chi-Fai
CF
School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Jiang
Jing-Jing
JJ
Leung
Kwok-Nam
KN
Fung
Kwok-Pui
KP
Lau
Clara Bik-San
CB
D000364:Agaricus; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D010936:Plant Extracts; D011134:Polysaccharides