Insights into the mechanism of antiproliferative effects of primaquine-cinnamic acid conjugates on MCF-7 cells (CROSBI ID 250991)
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Mabeta, Peace ; Pavić, Kristina ; Zorc, Branka
engleski
Insights into the mechanism of antiproliferative effects of primaquine-cinnamic acid conjugates on MCF-7 cells
In our previous paper we have shown that three primaquine-cinnamic acid conjugates composed of primaquine (PQ) residue and cinnamic acid derivatives (CADs) bound directly by an amide linkage (1) or through an acylsemicarbazide spacer (2 and 3) had significant growth inhibitory effects on some of the cancer cell lines. Compound 1 induced significant growth inhibition in the colorectal adenocarcinoma (SW620), human breast adenocarcinoma (MCF-7) and cervical carcinoma (HeLa) cell lines, while compounds 2 and 3 selectively inhibited the growth of MCF-7 cells. To better understand the underlying mechanisms of action of these PQ-CADs, morphological studies of the effects of the tested compounds on MCF-7 cells were undertaken using hematoxylin and eosin stain. Further analysis to determine the effects of the compounds on caspase activity and on the levels of apoptosis proteins were undertaken using the enzyme-linked immunosorbent assay (ELISA). Haematoxylin and eosin staining revealed that compounds 1 and 3 induced morphological changes in MCF-7 cells characteristic of apoptosis, while 2-treated cells were in interphase. Cell cycle analysis showed that cells treated with 1 and 3 were in sub-G1, while cells treated with 2 were mainly in interphase (G1 phase). Further, our study showed that the treatment of MCF-7 cells with 1 and 3 resulted in PARP cleavage as well as caspase-9 activation, indicating that they induced apoptotic cell death. In addition, compounds 1 and 3 inhibited the migration and invasion of MCF-7 cells, while compound 2 had marginal effect on cell migration and invasion.
primaquine ; cinnamic acid ; MCF-7 ; Bad ; p53 ; PARP ; migration and invasion
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