Kazinol C from Broussonetia kazinoki activates AMP-activated protein kinase to induce antitumorigenic effects in HT-29 colon cancer cells.
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.
Department of Biological Science and the Research Center for Women's Diseases, Sookmyung Women's University, Yongsan-Gu, Seoul 140-742, Republic of Korea.
Hak-Su
HS
Kim
Department of Biological Science and the Research Center for Women's Diseases, Sookmyung Women's University, Yongsan-Gu, Seoul 140-742, Republic of Korea.
Jihyun
J
Lim
Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Yongsan-Gu, Seoul 140-742, Republic of Korea.
Da Yeon
DY
Lee
Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Yongsan-Gu, Seoul 140-742, Republic of Korea.
Jae-Ha
JH
Ryu
Department of Biological Science and the Research Center for Women's Diseases, Sookmyung Women's University, Yongsan-Gu, Seoul 140-742, Republic of Korea.
Jong-Seok
JS
Lim
D000263:Adenylate Kinase / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D031623:Broussonetia / Q000737:chemistry; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D019073:HT29 Cells; D045782:Hemiterpenes / Q000494:pharmacology*; D006801:Humans; D012118:Resorcinols / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D020536:Enzyme Activators; D045782:Hemiterpenes; D012118:Resorcinols; C000599716:kazinol C; D000263:Adenylate Kinase