Inhibition of attachment and chemotactic invasion of uterine endometrial cancer cells by a new vinca alkaloid, conophylline.
The effect of conophylline, a new vinca alkaloid that inhibits ras expression, on tumour cell adhesion and infiltration was evaluated using a human endometrial cancer cell line. When SNG-II, a highly differentiated human endometrial cancer cell line, was exposed to conophylline, the cells developed filamentous processes at concentrations which did not affect cell proliferation (0.03-0.3 microgram/ml). After exposure to conophylline (0.3 microgram/ml), cells adherent to matrigel- and type IV collagen-coated wells respectively decreased to 26.9% and 33.3% of the number in the untreated control culture (p < 0.01). In an in vitro invasion assay using a Boyden chamber, infiltration of cells exposed to conophylline decreased to 19.4% (0.3 microgram/ml) (p < 0.01) of the control. In a wound assay, conophylline inhibited the movement of cells at 24 hr after wounding. Flow cytometric analysis revealed that expression of integrin beta 1 was not altered by conophylline, but E-cadherin and CD44 were decreased. The expression of E-cadherin and CD44 could be changed by conophlline.
Irie
T
T
Department of Obstetrics and Gynecology, School of Medicine, Keio University 35, Tokyo, Japan.
Kubushiro
K
K
Suzuki
K
K
Tsukazaki
K
K
Umezawa
K
K
Nozawa
S
S
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured; D014748:Vinca Alkaloids / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D014748:Vinca Alkaloids; C099167:conophylline