PCK3145 inhibits proliferation and induces apoptosis in breast and colon cancer cells.
OBJECTIVE
To explore the effects of PCK3145 beyond prostate cancer.


METHODS
Using Trypan blue, MTT proliferation assays, cell cycle and apoptosis analysis, we assessed the effects of PCK3145 on prostate (PC-3), breast (MCF-7) and colon (HT-29) human cancer cell lines and in osteosarcoma (MG-63) cells; any synergistic effects with docetaxel and oxaliplatin were also explored.


RESULTS
PCK3145 inhibited proliferation and induced apoptosis of PC-3, MCF-7 and HT-29 cells in a dose- and time-dependent manner but not in the MG-63 cell line, consistent with the low expression of the laminin receptor (LR) in the latter cell line. PCK3145 produced rapid (within 5 min) and transient (up to 60 min) activation of MEK and ERK1/2. Synergistic effects were observed with docetaxel and oxaliplatin.


CONCLUSIONS
PCK3145 can exert anticancer activity not only on prostate but also on breast and colon cancer cells, possibly through LR-mediated activation of MEK and ERK1/2 phosphorylation.
Laboratory of Pharmacokinetics, Department of Pharmacy, University of Patras, Patras, Greece.
Antonios
A
Kostopoulos
Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Efstathia
E
Papageorgiou
Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Michael
M
Koutsilieris
Laboratory of Pharmacokinetics, Department of Pharmacy, University of Patras, Patras, Greece gsivolap@upatras.gr.
Gregory
G
Sivolapenko
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010446:Peptide Fragments / Q000494:pharmacology*; D029584:Prostatic Secretory Proteins / Q000494:pharmacology*; D017474:Receptors, Laminin / Q000032:analysis; D043823:Taxoids / Q000494:pharmacology
D009944:Organoplatinum Compounds; D010446:Peptide Fragments; D029584:Prostatic Secretory Proteins; D017474:Receptors, Laminin; D043823:Taxoids; D000077150:Oxaliplatin; D000077143:Docetaxel; C506581:tigapotide
ERK; PCK3145; PSP94; breast cancer; colon cancer; laminin receptor; prostate cancer