PC-SPES inhibits cell proliferation by modulating p21, cyclins D, E and B and multiple cell cycle-related genes in prostate cancer cells.
PC-SPES is an herbal mixture, with evidence of clinical efficacy against prostate cancer (CaP), recently attracting tremendous attention. Using immunoblot and cell cycle specific cDNA array analyses, we investigated effects of PC-SPES on LNCaP, a hormone-dependent prostate cancer cell line. PC-SPES inhibited expression of cyclins D and E, inhibited Rb phosphorylation, switching it to a G1-to-S inhibitory state. Moreover, cDNA array analysis showed that PC-SPES caused up-regulation of p21(WAF1/CIP1) and decreased expression of cyclin B, Nedd8, cdc2, skp1, PCNA, MAD2L1, cyclin H, CKS2, E2F, Rbx1, MCM2, MCM5, Mpp2, Cullin-Cul4A, Cks1p9 and McM7, which are involved in cell cycle progression. Taken together, our results provide a mechanistic explanation for antiproliferative and antitumor effects of PC-SPES, suggesting that induction of CDK inhibitors and downregulation of cyclins leads to dephosphorylation of Rb and growth arrest.
Lu
Xiaohua
X
Department of Biochemistry and Molecular Biology, Basic Sciences Building, New York Medical College, Valhalla, NY 10595, USA.
Guo
Junqiao
J
Hsieh
Tze-chen
TC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004365:Drugs, Chinese Herbal; D005057:Eukaryotic Cells / Q000187:drug effects* / Q000201:enzymology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D018816:Genes, cdc / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D016160:Retinoblastoma Protein / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; C114209:herbal preparation PC-SPES; D017430:Prostate-Specific Antigen