Hinesol, a compound isolated from the essential oils of Atractylodes lancea rhizome, inhibits cell growth and induces apoptosis in human leukemia HL-60 cells

• Published in: Journal of natural medicines Vol. 69; no. 3; pp. 332 - 339
• Main Authors: Masuda, Yutaka, Kadokura, Takayuki, Ishii, Maki, Takada, Kimihiko, Kitajima, Junichi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.07.2015
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Atractylodes - chemistry; Biomedical and Life Sciences; Biomedicine; Cell Cycle; Cell Proliferation - drug effects; Complementary & Alternative Medicine; DNA Fragmentation; Drug Screening Assays, Antitumor; HL-60 Cells; Humans; Inhibitory Concentration 50; JNK Mitogen-Activated Protein Kinases - metabolism; Leukemia; MAP Kinase Signaling System; Medicinal Chemistry; Oils, Volatile - pharmacology; Original Paper; Pharmacology/Toxicology; Pharmacy; Plant Extracts - pharmacology; Plant Sciences; Rhizome - chemistry; Sesquiterpenes - pharmacology; Spiro Compounds - pharmacology; Essential oil; Hinesol; HL-60 cells; JNK; rhizome; Apoptosis
• ISSN: 1340-3443; 1861-0293
• DOI: 10.1007/s11418-015-0897-5

Hinesol is a unique sesquiterpenoid isolated from the Chinese traditional medicine, Atractylodes lancea rhizome. In a previous study, we screened various natural products in human leukemia HL-60 cells and identified an essential oil fraction from A. lancea rhizome that exhibited apoptosis-inducing activity in these cells; hinesol was subsequently shown to be the compound responsible for this apoptosis-inducing activity. In this study, we describe the cytotoxic effects and molecular mechanisms of hinesol in HL-60 cells. The antitumor effect of hinesol was associated with apoptosis. When HL-60 cells were treated with hinesol, characteristic features of apoptosis, such as nuclear fragmentation and DNA fragmentation, were observed. These growth-inhibitory and apoptosis-inducing activities of hinesol in leukemia cells were much stronger than those of β-eudesmol, another compound isolated from the essential oil fraction. Furthermore, hinesol induced activation of c-Jun N-terminal kinase (JNK), but not p38, prior to the onset of apoptosis. These results suggested that hinesol induced apoptosis through the JNK signaling pathway in HL-60 cells. Therefore, hinesol may represent a novel medicinal drug having indications in the treatment of various cancers, including leukemia.