Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K/Akt pathway.

Abstract

Isoegomaketone (IK) is a major biologically active component of Perilla frutescens. In this study, we investigated the contribution of reactive oxygen species (ROS) to IK-induced apoptosis in human melanoma SK-MEL-2 cells. We found that IK inhibited the proliferation of SK-MEL-2 human melanoma cells in a dose-dependent manner. IK also induced sub-G1 DNA accumulation, formation of apoptotic bodies, nuclear condensation, and a DNA ladder in SK-MEL-2 cells. IK also induced activation of caspase-3 and -9, whereas caspase‑8 was unaffected. Further, N-acetyl-L-cysteine (NAC, ROS scavenger) treatment to SK-MEL-2 cells significantly reduced IK-induced cell death. Pretreatment of NAC to SK-MEL-2 cells followed by 100 µM IK reduced the protein levels of Bax and cytochrome c as well as PARP cleavage, whereas the protein level of Bcl-2 increased. Moreover, IK inhibited the phosphorylation of AKT/mTOR protein and cell proliferation induced by LY294002, a PI3K inhibitor. In conclusion, IK-induced ROS generation regulates cell growth inhibition and it induces apoptosis through caspase‑dependent and -independent pathways via modulation of PI3K/AKT signaling in SK-MEL-2 cells.

• Authors: Soon-Jae Kwon, Ju-Hye Lee, Kwang-Deog Moon, Il-Yun Jeong, Sung-Tae Yee, Mi-Kyung Lee, Kwon-Il Seo
• Journal: International journal of oncology (Int J Oncol) Vol. 45 Issue 5 Pg. 1969-76 (Nov 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 25119993 (Publication Type: Journal Article)

Chemical References

• Chromones
• Furans
• Ketones
• Morpholines
• isoegomaketone
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Chromones
• Furans (administration & dosage)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Ketones (administration & dosage)
• Melanoma (drug therapy, genetics, pathology)
• Mitochondria (genetics, pathology)
• Morpholines
• Phosphatidylinositol 3-Kinases (biosynthesis, genetics)
• Proto-Oncogene Proteins c-akt (biosynthesis, genetics)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (biosynthesis)