Sustained ERK activation is involved in the kaempferol-induced apoptosis of breast cancer cells and is more evident under 3-D culture condition

Bong Woo Kim, Eung Ryoung Lee, Hye Min, Hyo Soon Jeong, Jae Yeon Ahn, Jung Hyun Kim, Hye Yeon Choi, Hana Choi, Young Kim Eun, Pill Park Se, Ssang Goo Cho

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1080-1089
Number of pages10
JournalCancer Biology and Therapy
Issue number7
StatePublished - Jul 2008
Externally publishedYes


  • 3-D culture condition
  • Apoptosis
  • Breast cancer
  • ERK activation
  • Kaempferol
  • Mitogen-activated protein kinase
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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