Sustained ERK activation is involved in the kaempferol-induced apoptosis of breast cancer cells and is more evident under 3-D culture condition.
In order to determine the effects of a variety of flavonoids, we applied differing amounts of several flavonoids to human breast cancer cells. Kaempferol treatment resulted in significant reduction of cell viability in the MCF-7 cells, although it exerted only minor effect on the cell viability of MDA-MB-231 or mammary epithelial HC-11 cells. Kaempferol was demonstrated to induce sustained ERK activation concomitantly with MEK1 and ELK1 activation, and this kaempferol-induced apoptosis was suppressed by treatment with PD98059, the overexpression of a kinase-inactive ERK mutant, or ERK siRNA. Kaempferol treatment was shown to profoundly induce the generation of fluorescent DCF in the MCF-7 cells, and treatment with N-acetyl cysteine suppressed kaempferol-induced PARP cleavage. Moreover, because breast cancer is associated with increased collagen synthesis and accumulation, we utilized a collagen-based 3D culture method. Under the 3-dimensional culture condition employed herein, kaempferol treatment was shown to result in a significant reduction in cell viability, an effect which occurred in a dose-dependent manner. Compared with what was observed under conventional 2D culture condition, we observed more evident apoptotic cell death and ERK activation as the result of kaempferol treatment in a collagen-based 3D culture environment. Similar to the case of conventional 2D cultured cells, the addition of PD98059 significantly suppressed intracellular ROS production. Collectively, these results show that the sustained activation of the ERK signaling pathway is markedly involved in kaempferol-induced apoptosis of breast cancer MCF-7 cells, and that this effect is more evident under 3D culture condition.
Kim
Bong-Woo
BW
Department of Animal Biotechnology and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
Lee
Eung-Ryoung
ER
Min
Hye-Min
HM
Jeong
Hyo-Soon
HS
Ahn
Jae-Yeon
JY
Kim
Jung-Hyun
JH
Choi
Hye-Yeon
HY
Choi
Hana
H
Kim
Eun Young
EY
Park
Se Pill
SP
Cho
Ssang-Goo
SG
D017209:Apoptosis; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases; D005434:Flow Cytometry; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D018613:Microscopy, Confocal / Q000379:methods; D017382:Reactive Oxygen Species
D004791:Enzyme Inhibitors; D044949:Kaempferols; D017382:Reactive Oxygen Species; C006552:kaempferol; D048049:Extracellular Signal-Regulated MAP Kinases