Semisynthetic oleanane triterpenoids inhibit migration and invasion of human breast cancer cells through downregulated expression of the ITGB1/PTK2/PXN pathway.
This paper reports a study on the role of two synthetic derivatives of oleanolic acid (OA), HIMOXOL and Br-HIMOLID, in the regulation of cell migration and invasion and the underlying molecular mechanisms of breast cancer cells. The effect of the compounds on four breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-468, and T-47D) and also on noncancerous breast cells, MCF-12A, was reported. The compounds had no effect on the migration of MCF-12A cells. However, both the derivatives revealed a higher cytotoxicity than the maternal compound OA, and in sub-cytotoxic concentrations, they decreased the migration of MCF7, MDA-MB-231, and MDA-MB-468 breast cancer cells and also the invasion of MCF7 and MDA-MB-231 cells; although, the derivatives had no effect on the migration and invasion of T-47D cells. Both the derivatives of OA inhibited the cell migratory and invasive abilities of breast cancer cells by downregulating the expressions of ITGB1, PTK2, and PXN genes and by decreasing the phosphorylation status and the level of its respective proteins (integrin β1, FAK, and paxillin, respectively). This study is the first to report the antimigratory and anti-invasive activities of HIMOXOL and Br-HIMOLID in breast cancer cells.
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland. Electronic address: nlisiak@ump.edu.pl.
Natalia
N
Lisiak
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland.
Anna
A
Paszel-Jaworska
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland.
Ewa
E
Totoń
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland.
Błażej
B
Rubiś
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland; Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str, 61-848 Poznan, Poland.
Martyna
M
Pakuła
Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, 6 Grunwaldzka Str, 60-780 Poznan, Poland.
Barbara
B
Bednarczyk-Cwynar
Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, 6 Grunwaldzka Str, 60-780 Poznan, Poland.
Lucjusz
L
Zaprutko
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland.
Maria
M
Rybczyńska
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
C000617653:12-bromo-3-hydroxyimonoolean-28-13-olide; D000970:Antineoplastic Agents; D019012:Integrin beta1; C496061:PXN protein, human; D051419:Paxillin; C587228:methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate; D009828:Oleanolic Acid; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
Breast cancer; Invasion; Migration; Semisynthetic triterpenoids