Masuda Yutaka, Kadokura Takayuki, Ishii Maki, Takada Kimihiko, Kitajima Junichi
Laboratory of Clinical Pharmacy, Showa Pharmaceutical University, Higashi Tamagawa Gakuen, Machida, Tokyo, 194-8543, Japan,
J Nat Med. 2015 Jul;69(3):332-9. doi: 10.1007/s11418-015-0897-5. Epub 2015 Apr 2.
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.
海蒎内酯是从中药茅苍术根茎中分离得到的一种独特的倍半萜类化合物。在之前的一项研究中，我们在人白血病HL - 60细胞中筛选了各种天然产物，并从茅苍术根茎中鉴定出一种精油组分，该组分在这些细胞中表现出凋亡诱导活性；随后证明海蒎内酯是负责这种凋亡诱导活性的化合物。在本研究中，我们描述了海蒎内酯在HL - 60细胞中的细胞毒性作用和分子机制。海蒎内酯的抗肿瘤作用与凋亡相关。当用海蒎内酯处理HL - 60细胞时，观察到凋亡的特征性特征，如核碎裂和DNA片段化。海蒎内酯在白血病细胞中的这些生长抑制和凋亡诱导活性比从精油组分中分离出的另一种化合物β - 桉叶醇要强得多。此外，在凋亡开始之前，海蒎内酯诱导c - Jun氨基末端激酶（JNK）的激活，但不诱导p38的激活。这些结果表明，海蒎内酯通过JNK信号通路在HL - 60细胞中诱导凋亡。因此，海蒎内酯可能代表一种新型药物，可用于治疗包括白血病在内的各种癌症。
