Regulation of apoptosis by modified naringenin derivatives in human colorectal carcinoma RKO cells

Eung Ryoung Lee, Yong Jin Kang, Hyun Jeong Kim, Hye Yeon Choi, Geun Ho Kang, Jung Hyun Kim, Bong Woo Kim, Hyo Soon Jeong, Yong Sun Park, Ssang Goo Cho

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Flavonoids are micronutrients that are widely detected in foods of plant origin and have been ascribed pharmacological properties. Several biological functions of flavonoids have been thus far identified, whereas there currently exists a lack of evidence to support the relationship between the structure-activity relationship and apoptosis-inducing activity. In an attempt to determine the importance of the OH group or substitution of the 5- or 7-carbon in the diphenylpropane skeleton of flavonoids, we selected 14 different flavonoids with different structures, particularly with regard to the 5- or 7-carbon, and found that naringenin treatment caused a slight decrease in the cell viability of the human colorectal carcinoma RKO cells. Next, in order to characterize the effects of specific substitutions of the 7-carbon of naringenin on apoptosis-regulatory activities, and in an attempt to develop anti-proliferative flavonoid derivatives that would be more effective against colon cancer, we originally synthesized several modified naringenin derivatives (MNDs) including 7-O-benzyl naringenin (KUF-1) and 7-O-(m-metoxybenzyl) naringenin (KUF-2). Treatment with KUF-1 or KUF-2 resulted in significant apoptosis-inducing effects concomitant with losses in mitochondrial membrane potential, caspase activation, intracellular ROS production, and sustained ERK activation. Our data show that KUF-1 or KUF-2 regulate the apoptosis of RKO cells via intracellular ROS production coupled with the concomitant activation of the ERK signaling pathway, thereby implying that hydroxylation or substitution at C7 is critical for the apoptosis-inducing activity of flavonoids.

Original languageEnglish (US)
Pages (from-to)259-273
Number of pages15
JournalJournal of Cellular Biochemistry
Issue number1
StatePublished - May 1 2008
Externally publishedYes


  • Apoptosis
  • ERK
  • Flavonoid
  • Modified naringenin derivatives
  • Naringenin
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Regulation of apoptosis by modified naringenin derivatives in human colorectal carcinoma RKO cells'. Together they form a unique fingerprint.

Cite this