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Kazinol C from Broussonetia kazinoki activates AMP-activated protein kinase to induce antitumorigenic effects in HT-29 colon cancer cells.

Abstract
Kazinol C is a 1,3-diphenylpropane, obtained from Broussonetia kazinoki, that has been employed in folk medicine as an edema suppressant. It exerts beneficial effects in oxidative stress-related diseases, such as cancer. However, the molecular mechanism involved in the anticancer effects remains to be determined. AMP-activated protein kinase (AMPK) has emerged as a possible anticancer target molecule. The present study investigated the effect of kazinol C on AMPK activation as well as subsequent HT-29 colon cancer cell viability, apoptosis and migration. Kazinol C markedly induced AMPK phosphorylation and significantly attenuated HT-29 colon cancer cell growth and viability. Compound C, as a well‑known AMPK inhibitor, blocked the kazinol C-induced cell death, and stable transduction of dominant-negative (DN) AMPK in colon cancer cells also inhibited kazinol C-induced cell apoptosis. In addition, kazinol C inhibited HT-29 cell migration and anchorage-independent growth. AMPK inhibition using stable transduction with DN AMPK significantly abrogated the kazinol C-induced inhibition of cancer cell migration. Thus, AMPK is a critical and novel regulator of kazinol C-mediated cancer cell apoptosis and inhibition of migration, suggesting that AMPK is a prime cancer target.
AuthorsHak-Su Kim, Jihyun Lim, Da Yeon Lee, Jae-Ha Ryu, Jong-Seok Lim
JournalOncology reports (Oncol Rep) Vol. 33 Issue 1 Pg. 223-9 (Jan 2015) ISSN: 1791-2431 [Electronic] Greece
PMID25394483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Drugs, Chinese Herbal
  • Enzyme Activators
  • Hemiterpenes
  • Resorcinols
  • kazinol C
  • Adenylate Kinase
Topics
  • Adenylate Kinase (metabolism)
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Apoptosis
  • Broussonetia (chemistry)
  • Cell Adhesion
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Drug Screening Assays, Antitumor
  • Drugs, Chinese Herbal (pharmacology)
  • Enzyme Activation
  • Enzyme Activators (pharmacology)
  • HT29 Cells
  • Hemiterpenes (pharmacology)
  • Humans
  • Resorcinols (pharmacology)

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