Honokiol induces apoptosis and suppresses migration and invasion of ovarian carcinoma cells via AMPK/mTOR signaling pathway.

Abstract

Honokiol, a natural biphenolic compound, exerts anticancer effects through a variety of mechanisms on multiple types of cancer with relatively low toxicity. Adenosine 5'‑phosphate‑activated protein kinase (AMPK), an essential regulator of cellular homeostasis, may control cancer progression. The present study aimed to investigate whether the anticancer activities of honokiol in ovarian cancer cells were mediated through the activation of AMPK. Honokiol decreased cell viability of 2 ovarian cancer cell lines, with an half‑maximal inhibitory concentration value of 48.71±11.31 µM for SKOV3 cells and 46.42±5.37 µM for Caov‑3 cells. Honokiol induced apoptosis via activation of caspase‑3, caspase‑7 and caspase‑9, and cleavage of poly‑(adenosine 5'‑diphosphate‑ribose) polymerase. Apoptosis induced by honokiol was weakened by compound C, an AMPK inhibitor, suggesting that honokiol‑induced apoptosis was dependent on the AMPK/mechanistic target of rapamycin signaling pathway. Additionally, honokiol inhibited the migration and invasion of ovarian cancer cells. The combined treatment of honokiol with compound C reversed the activities of honokiol in wound healing and Matrigel invasion assays. These results indicated that honokiol may have therapeutic potential in ovarian cancer by targeting AMPK activation.

• Authors: Jin Sun Lee, Ji Young Sul, Jun Beom Park, Myung Sun Lee, Eun Young Cha, Young Bok Ko
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 43 Issue 5 Pg. 1969-1978 (May 2019) ISSN: 1791-244X [Electronic] Greece
• PMID: 30864681 (Publication Type: Journal Article)

Chemical References

• Biphenyl Compounds
• Lignans
• honokiol
• MTOR protein, human
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Apoptosis (drug effects)
• Biphenyl Compounds (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Enzyme Activation (drug effects)
• Female
• Humans
• Lignans (pharmacology)
• Mice
• Models, Biological
• NIH 3T3 Cells
• Neoplasm Invasiveness
• Ovarian Neoplasms (enzymology, pathology)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Tumor Stem Cell Assay