Effect of pentosan, a novel cancer chemotherapeutic agent, on prostate cancer cell growth and motility.
Pentosan is a new chemotherapeutic drug which is currently in Phase I clinical trials. In our experimental systems, in vivo, pentosan inhibits the growth of the highly metastatic MAT-LyLu (MLL) Dunning R3327 prostate cancer cell line only at toxic doses and has no apparent effect on growth in vitro. The mechanism of tumor inhibition of this drug is unknown; however, in vitro, pentosan exhibits a potent inhibition of cell motility. Cell motility is essential for tumor cell metastasis and angiogenesis. By blocking cell motility, pentosan has the potential to inhibit both tumor growth and metastasis. We have characterized the mechanism of motility inhibition by pentosan and believe it alters cell-extracellular matrix interactions. The mechanism of motility inhibition by pentosan appears to be independent of cytoskeletal structural alterations, including changes in microfilament and microtubule networks. Pentosan acts through a different mechanism than suramin, a drug which inhibits motility through inhibition of growth factor effects. In vitro, pentosan alters cellular contacts with the extravascular matrix and inhibits cell motility. In vivo, pentosan prolongs survival of rats injected with MLL cells by 25%, but did not appear to decrease the rate of primary tumor growth or the number of metastatic lesions in the treated animals. These data suggest that, in vivo, pentosan acts through an as yet undefined mechanism.
Pienta
K J
KJ
Meyer L. Prentis Comprehensive Cancer Center, Wayne State University School of Medicine, Detroit, Michigan.
Murphy
B C
BC
Isaacs
W B
WB
Isaacs
J T
JT
Coffey
D S
DS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D008297:Male; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010426:Pentosan Sulfuric Polyester