Synthesized tetrahydroisoquinoline alkaloid exerts anticancer effects at least in part by suppressing NF-κB-regulated proteins in A549 human lung cancer cells

  • Oncol Rep. 2015 Mar;33(3):1141-6. doi: 10.3892/or.2014.3658.
Won Sup Lee  1 ,  Jeong Won Yun  1 ,  Arulkumar Nagappan  1 ,  Jing Nan Lu  1 ,  Min Jeong Kim  1 ,  Jeong-Hee Lee  2 ,  Dong Hoon Kim  3 ,  Yung Hyun Choi  4 ,  Hye Jung Kim  5 ,  Ki Churl Chang  4 ,  Jin-Myung Jung  6
Affiliations
  • 1. Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
  • 2. Department of Pathology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
  • 3. Department of Emergency Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
  • 4. Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
  • 5. Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 program), Dongeui University Graduate School, Busan 614-052, Republic of Korea.
  • 6. Department of Neurosurgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
PMID: 25482101 DOI: 10.3892/or.2014.3658
Abstract

CKD-712, a newly synthesized tetrahydroisoquinoline (THI) and an enantiomer (S form) of YS 49 (a derivative of higenamine) has been reported to suppress nuclear factor-κB (NF-κB) activity in normal cells. In the present study, we investigated the Anticancer effects of THI at a low concentration where CKD-712 did not induce cell death in normal cells. At the range of concentrations used, CKD-712 induced cell growth arrest, and inhibited the invasion and motility of A549 cells as determined by cell cycle analysis, a Matrigel-coated chamber assay, and a wound-healing assay, respectively. CKD-712 suppressed MMP-9, but not MMP-2 and Other NF-κB-regulated proteins involved in Cancer metastasis such as VEGF. Moreover, CKD-712 induced cell cycle arrest at G2M phase by suppressing cyclin A, cyclin B and CDK-1 expression. Taken together, these data suggested that CKD-712 may exert Anticancer effects by suppressing NF-κB pathways and inducing cell cycle arrest at G2M phase.

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