Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University, Chengdu, 610041, PR China.
Toxicol Mech Methods. 2010 Jun;20(5):234-41. doi: 10.3109/15376511003758831.
Honokiol, an active component isolated and purified from Chinese traditional herb magnolia, has been shown to inhibit growth and induce apoptosis in different cancer cell lines. This study shows that honokiol can induce a cell death distinct from apoptosis at lower concentrations. The death was characterized by cytoplasmic vacuolization with the endoplasmic reticulum swelling and accompanied by apoptosis at higher concentrations in NB4 and K562 cells. The two death processes may be in sequence at lower concentrations and in parallel with the increase of honokiol concentration. Membrane-associated cytotoxicity was involved in honokiol-induced paraptosis and apoptosis. Furthermore, honokiol inhibited concentration-dependent cell adhesion to extracellular matrix for NB4 cells. In addition, the cytotoxicity of honokiol combined treatment with imatinib was schedule- and concentration-dependent and the sequential administration of honokiol before imatinib appeared to be more beneficial in K562 cells. Taken together, the data suggest that honokiol induced a novel cell death pathway and there was cross-talk between apoptotic and non-apoptotic programmed cell death caused by honokiol in leukemia cells. Moreover, honikiol exhibited schedule-dependent synergy in combination with imatinib and sequential administration of imatinib followed by honokiol could be the optimal sequence to combine these two drugs in K562 cells.
厚朴酚是从中国传统草药厚朴中分离和纯化得到的一种活性成分，已被证明能抑制不同癌细胞系的生长并诱导其凋亡。本研究表明，厚朴酚在较低浓度下能诱导一种不同于凋亡的细胞死亡。这种死亡的特征是细胞质空泡化，内质网肿胀，并在较高浓度下伴随着 NB4 和 K562 细胞的凋亡。这两种死亡过程可能在较低浓度下按顺序发生，随着厚朴酚浓度的增加而平行发生。膜相关的细胞毒性参与了厚朴酚诱导的paraptosis 和凋亡。此外，厚朴酚抑制 NB4 细胞对细胞外基质的浓度依赖性细胞黏附。此外，厚朴酚与伊马替尼联合治疗的细胞毒性呈时间和浓度依赖性，伊马替尼序贯给药在前似乎对 K562 细胞更有益。综上所述，数据表明厚朴酚诱导了一种新的细胞死亡途径，厚朴酚诱导的凋亡和非凋亡程序性细胞死亡之间存在相互作用。此外，厚朴酚与伊马替尼联合应用具有时间依赖性协同作用，伊马替尼序贯给药后给予厚朴酚可能是 K562 细胞中联合应用这两种药物的最佳顺序。
