Abstract
γ-Bisabolene has demonstrated antiproliferative activities against several human cancer cell lines. This study first discloses the antiproliferative and apoptosis induction activities of γ-bisabolene to human neuroblastoma TE671 cells. A CC50 value of γ-bisabolene was 8.2 μM to TE671 cells. Cell cycle analysis with PI staining showed γ-bisabolene elevating the sub-G1 fractions in a time-dependent manner. In addition, annexin V-FITC/PI staining showed γ-bisabolene significantly triggering early (annexin-V positive/PI negative) and late (annexin-V positive/PI positive) apoptosis in dose-dependent manners. γ-Bisabolene induced caspase 3/8/9 activation, intracellular ROS increase, and mitochondrial membrane potential decrease in apoptosis of human neuro-blastoma cells. Moreover, γ-bisabolene increased p53 phosphorylation and up-regulated p53-mediated apoptotic genes Bim and PUMA, as well as decreased the mRNA and protein levels of CK2α. Notably, the results indicated the involvement of CK2α-p53 pathways in mitochondria-mediated apoptosis of human neuroblastoma cells treated with γ-bisabolene. This study elucidated the apoptosis induction pathways of γ-bisabolene-treated neuroblastoma cells, in which could be useful for developing anti-neuroblastoma drugs.
Highlights
Neuroblastoma is a tumor of neural progenitor cells, which widely metastasizes to skin, bone marrow, liver, and non-contiguous lymph nodes, and becomes the most common extracranial solid tumor in children [1]
Forγ-bisabolene antiproliferative assay (B), TE671 cells were grown in the indicatedcyclohex-1-ene) concentrations of was shown (A)
For antiproliferative assay (B), TE671 cells were grown in the indicated concentrations γ-bisabolene for 48 h
Summary
Neuroblastoma is a tumor of neural progenitor cells, which widely metastasizes to skin, bone marrow, liver, and non-contiguous lymph nodes, and becomes the most common extracranial solid tumor in children [1]. The infant patients with metastasis only to skin, bone marrow, and liver have the good prognosis post treatment with the current anticancer drugs. The 5-year event-free survival rate of children with disseminated neuroblastoma (Stage 4) is still less than 40%. Molecules 2016, 21, 601 recurrence the development of novel anti-neuroblastoma agents is still recommended to Molecules[2]. The development of novel anti-neuroblastoma is still recommended Apoptotic[2]. Inducers have been widely regarded as potential agents anti-cancer therapeutics and to improve the patient outcomes.
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