Discipline of Microbiology and Immunology (M502), School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
Cancer Chemother Pharmacol. 2010 Apr;65(5):877-88. doi: 10.1007/s00280-009-1093-7. Epub 2009 Aug 13.
To examine the in vitro anticancer activity of Melaleuca alternifolia (tea tree) oil (TTO), and its major active terpene component, terpinen-4-ol, against two aggressive murine tumour cell lines, AE17 mesothelioma and B16 melanoma.
Effects of TTO and terpinen-4-ol on the cellular viability of two tumour cell lines and fibroblast cells were assessed by MTT assay. Induction of apoptotic and necrotic cell death was visualised by fluorescent microscopy and quantified by flow cytometry. Tumour cell ultrastructural changes were examined by transmission electron microscopy and changes in cell cycle distribution were assessed by flow cytometry, with changes in cellular morphology monitored by video time lapse microscopy.
TTO and terpinen-4-ol significantly inhibited the growth of two murine tumour cell lines in a dose- and time-dependent manner. Interestingly, cytotoxic doses of TTO and terpinen-4-ol were significantly less efficacious against non-tumour fibroblast cells. TTO and terpinen-4-ol induced necrotic cell death coupled with low level apoptotic cell death in both tumour cell lines. This primary necrosis was clarified by video time lapse microscopy and also by transmission electron microscopy which revealed ultrastructural features including cell and organelle swelling following treatment with TTO. In addition, both TTO and terpinen-4-ol induced their inhibitory effect by eliciting G1 cell cycle arrest.
TTO and terpinen-4-ol had significant anti-proliferative activity against two tumour cell lines. Moreover, the identification of primary necrotic cell death and cell cycle arrest of the aggressive tumour cells highlights the potential anticancer activity of TTO and terpinen-4-ol.
研究互叶白千层（茶树）油（TTO）及其主要活性萜烯成分萜品-4-醇对两种侵袭性鼠肿瘤细胞系 AE17 间皮瘤和 B16 黑色素瘤的体外抗癌活性。
通过 MTT 法评估 TTO 和萜品-4-醇对两种肿瘤细胞系和成纤维细胞的细胞活力的影响。通过荧光显微镜观察和流式细胞术定量观察诱导的凋亡和坏死细胞死亡。通过透射电子显微镜观察肿瘤细胞超微结构的变化，通过流式细胞术评估细胞周期分布的变化，并通过视频延时显微镜监测细胞形态的变化。
TTO 和萜品-4-醇以剂量和时间依赖的方式显著抑制两种鼠肿瘤细胞系的生长。有趣的是，TTO 和萜品-4-醇对非肿瘤成纤维细胞的细胞毒性剂量的疗效明显较低。TTO 和萜品-4-醇在两种肿瘤细胞系中诱导坏死性细胞死亡，并伴有低水平的凋亡细胞死亡。这一原发性坏死通过视频延时显微镜和透射电子显微镜得到了澄清，后者揭示了处理 TTO 后细胞和细胞器肿胀等超微结构特征。此外，TTO 和萜品-4-醇通过诱导 G1 细胞周期停滞发挥其抑制作用。
TTO 和萜品-4-醇对两种肿瘤细胞系具有显著的抗增殖活性。此外，侵袭性肿瘤细胞的原发性坏死细胞死亡和细胞周期阻滞的鉴定突出了 TTO 和萜品-4-醇的潜在抗癌活性。
