title: Anticancer activity of Honokiol against lymphoid malignant cells via activation of ROS-JNK and attenuation of Nrf2 and NF-κB.
abstract: OBJECTIVE
  To evaluate the effect of Honokiol (HK) in the ROS-JNK pro-apoptotic pathway and NF-κB, Nrf2 anti-apoptotic pathways, in order to seek a possible explanation for its anticancer efficacy.
  
  
  METHODS
  The Raji and Molt4 cell lines were utilized for the determination of anticancer activity against lymphoid malignant cells. BALB/C nude mice, weighing 18-20g each and aged 4-5 weeks, were procured from the central animal house facility. For establishing non-Hodgkin lymphoma in BALB/C, the nude mice were subcutaneously administered 1×10(7) Raji cells, suspended in 0.2 mL sterile PBS on the back. The mice were then randomly divided into 3 groups (6 mice in each group). HK cytotoxicity was determined using the colorimetric MTT assay.
  
  
  RESULTS
  In colorimetry-based MTT assay, the cytotoxicity of HK was determined at different time intervals, in lymphoid malignant Raji and Molt4 cell lines. HK exhibited prominent cytotoxicity against Raji cell lines with IC50 of 0.092 ± 0.021 μM. In Molt4 cells, the administration of HK caused significant cytotoxicity with IC50 of 0.521 ± 0.115 μM. The treatment of HK caused significant increase in the activity of reactive oxygen species (ROS) in Raji cells at various time intervals. Moreover, the level of NF-κB was significantly reduced in the presence of HK, which could be easily understood by a decreased level of p-65. Furthermore, in the presence of ROS inhibitor NAC (10mM) for 24 hrs, the JNK pathway was markedly activated, together with inhibition of NF-κB activity and a reduced level of Nrf2 expression. To further confirm the in vitro results by in vivo activity, HK was observed to inhibit the proliferation of Raji cells in vivo, which might be attributable to its inhibitory effect against the progression of the tumor (p<0.05).
  
  
  CONCLUSIONS
  The present study suggests that HK causes considerable induction of apoptosis in lymphoid malignant cells, both in vitro and in vivo, whereas the generation of ROS might serve as an underlying mechanism for inducing apoptosis.
authors: Department of Hematology, Hangzhou First People's Hospital, Hangzhou City, Zhejiang 310006, China.
authors: Da-Quan
authors: DQ
authors: Gao
authors: Shen'Xian
authors: S
authors: Qian
authors: Tong'Fa
authors: T
authors: Ju
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D017705:Lignans; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C495635:NFE2L2 protein, human; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols