Induction of apoptosis and down-regulation of bcl-6 in mutu I cells treated with ethanolic extracts of the Chinese herbal supplement PC-SPES.
PC-SPES, an HPLC-standardized 8-herb dietary supplement prepared by proprietary extraction/mixing technologies, appears to have a number of health benefits when given to cancer patients. These include reduction of serum PSA (prostate specific antigen) in individuals diagnosed with advanced prostate carcinoma, and overall improvement of morbidity and immune status in terminal cancer cases. Since the expression of bcl-6 in T and B lymphocytes has been reported to be significantly down regulated by mitogens, we reason that the immune boosting effects of PC-SPES could involve the modulation of bcl-6 expression. Such a hypothesis was tested in the bcl-6 abundant Mutu I cells. Specifically, we investigated the effects of PC-SPES in regulating cell growth, induction of apoptosis, effecting changes in the retinoblastoma gene RB and the modulation of expression of the bcl-6. Herein we report that proliferation of Mutu I cells was inhibited by a 3-7 day incubation with ethanolic extracts of PC-SPES, with concurrent induction of apoptosis. In addition, a dose-dependent reduction of bcl-6 was observed, with no concomitant change in either the phosphorylated or the unphosphorylated forms of RB. These data raise the possibility that PC-SPES may enhance immune functions in vivo by down-regulating bcl-6 expression. Alternatively, decrease in bcl-6 could serve as a biomarker for testing the efficaciousness of PC-SPES in vivo.
Hsieh
T C
TC
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Ng
C
C
Chang
C C
CC
Chen
S S
SS
Mittleman
A
A
Wu
J M
JM
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C114209:herbal preparation PC-SPES