lignans and Burkitt-Lymphoma

Sesamolin and sesamin are representative lignans found in sesame seed. The present study was designed to demonstrate the anti-cancer activity of sesamolin achieved by increasing the expression level of NKG2D ligands on Raji cells, which are derived from Burkitt's lymphoma. The anti-cancer activity of sesamolin was also compared with that of sesamin. The cytolysis activity of NK cells against Raji was elevated by the pretreatment of sesamolin on Raji, but not by sesamin. We found that higher NKG2D ligand expression increased the sensitivity of sesamolin-treated Raji to NK cell lysis, resulting from a more active ERK signaling pathway. Our results provide evidence that targeting the ERK signaling pathway may enhance the antitumor activity of lignans and that there is a potential immunotherapeutic value for cancer treatment.

Topics: Antineoplastic Agents; Burkitt Lymphoma; Cell Line, Tumor; Cytotoxicity, Immunologic; Dioxoles; Humans; Killer Cells, Natural; Lignans; MAP Kinase Signaling System; Molecular Targeted Therapy; NK Cell Lectin-Like Receptor Subfamily K; Seeds; Sesamum; Up-Regulation

This study was aimed to investigate the effect of Honokiol (HNK) combined with Gemcitabine (GEM) on the proliferation and apoptosis of human Burkitt lymphoma Raji cells. Cell proliferation was detected by CCK-8 method to study the role of Honokiol and Gemcitabine in Raji cells. The cell apoptosis and cell cycle status were analyzed by flow cytometry. The level of apoptosis-related protein BCL-2 was measured with Western blot. The results showed that compared with cells treated with mentioned above drugs alone, the proliferative potential of cells in combination group was significantly inhibited (P < 0.01) and the inhibition rate was related to the concentration and action time of HNK; and apoptosis rate markedly increased (P < 0.01), while most Raji cells were arrested at G0/G1 phase and decreased in S phase after treatment with combination of two drugs; the expression of BCL-2 protein decreased (P < 0.01). It is concluded that Honokiol combined Gemcitabine can synergistically inhibit the proliferation, induce cell apoptosis, and down-regulate the expression of BCL-2 in Raji cells. The possible mechanism of synergistic effect may be related with arrest of cell cycle at G0/G1 phase and downregulation of the expression of BCL-2.

Topics: Apoptosis; Biphenyl Compounds; Burkitt Lymphoma; Cell Line, Tumor; Cell Proliferation; Deoxycytidine; Drug Synergism; Gemcitabine; Humans; Lignans; Proto-Oncogene Proteins c-bcl-2

To investigate the apoptosis-inducing effect of honokiol on human non-Hodgkin lymphoma Raji cells and the possible mechanism.. Raji cells were treated with different concentrations of honokiol, and the proliferation of the cells was detected using MTT assay. Flow cytometry was employed to analyze the cell cycle changes and apoptosis of honokiol-treated cells. Caspase 8 activity in the cells was measured by caspase 8 kit, and RT-PCR was used to detect the expression of apoptosis-related genes Bcl-2, Bad, and Bax.. Honokiol significantly inhibited the growth of Raji cells in a time- and dose-dependent manner, with IC(50) concentration of 17.53, 12.61, and 7.4 µg/ml at 12, 24, 48 h, respectively. Flow cytometry revealed cell cycle arrest at G0/G1 phase following honokiol treatment. The apoptosis rates of Raji cells treated with 7.5 and 15 µg/ml honokiol were significantly higher than that of the control cells [(18.24∓2.53)%, (28.44∓2.48)% vs (4.84∓1.15)%, P<0.01]. Caspase 8 activity in Raji cells was significantly enhanced by honokiol (P<0.05). The mRNA expression of the apoptosis-promoting gene Bad was significantly increased following honokiol treatment (P<0.01), while the expressions of Bcl-2 and Bax remained unchanged.. Honokiol can induce apoptosis in Raji cells possibly in relation to enhancement of caspase 8 activity and Bad gene expression.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; bcl-Associated Death Protein; Biphenyl Compounds; Burkitt Lymphoma; Caspase 8; Cell Line, Tumor; Cell Proliferation; Humans; Lignans; Lymphoma, Non-Hodgkin