Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin

Rok, strany: 2012, 361 - 369

The flavonol aglycone isorhamnetin shows anti-proliferative activity in a variety of cancer cells. Previous work, from our laboratory showed that isorhamnetin inhibits the proliferation of human esophageal squamous carcinoma Eca-109 cells in vitro, but only after 72 h of exposure. This led us to propose that isorhamnetin exposure induces a cellular stress response that inhibits the antiproliferative and apoptotic effects of the compound during early exposure. To test this hypothesis, the present study examined the effects of isorhamnetin on Eca-109 cells during the first 72 h of exposure. Cell growth was assessed using the trypan blue exclusion assay, and expression of IκBα, NF-κB/p65, NF-κB/p50, phospho-Akt, Bcl-2, COX-2, Mcl-1, Bax, p53 and Id-1 were analyzed by Western blot. During the first 72 h of exposure, NF-κB/p65 and NF-κB/p50 accumulated in nuclei and expression of COX-2, Bcl-2 and Mcl-1 increased. In contrast, expression of IκBα and Bax fell initially but later increased. Expression of phospho-Akt and p53 showed no detectable change during the first 48 h. Pretreatment with the NF-κB inhibitor MG132 before exposure to isorhamnetin blocked the nuclear accumulation of p50 and p65, thereby inhibiting cell proliferation. These results show that during early exposure of Eca-109 cells to isorhamnetin, the NF-κB signaling pathway is activated and COX-2 expression increases, and this increase in expression partially inhibits isorhamnetin-induced apoptosis. Beyond 72 h of exposure, however, the apoptotic effect of isorhamnetin dominates, leading to inhibition of the NF-κB pathway and of cellular proliferation. These results will need to be taken into account when exploring the use of isorhamnetin against cancer in vivo. Keywords: isorhamnetin, Eca-109, NF-κB, COX-2, cellular stress response

ISO 690:

Shi, C., Fan, L., Cai, Z., Liu, Y., Yang, C. 2012. Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin. In NEOPLASMA, vol. 59, no.4, pp. 361-369. 0028-2685.

APA:

Shi, C., Fan, L., Cai, Z., Liu, Y., Yang, C. (2012). Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin. NEOPLASMA, 59(4), 361-369. 0028-2685.