Modulatory Effects and Action Mechanisms of Tryptanthrin on Murine Myeloid Leukemia Cells

Leukemia is the disorder of hematopoietic cell development and is characterized by an uncoupling of cell proliferation and differentiation. There is a pressing need for the development of novel tactics for leukemia therapy as conventional treatments often have severe adverse side effects. Tryptanthrin （6,12-dihydro-6,12-dioxoindolo- （2,1-b）-quinazoline） is a naturally-occurring, weakly basic alkaloid isolated from the dried roots of medicinal indigo plants （Ban-Lan-Gen）. It has been reported to have various biological and pharmacological activities, including anti-microbial, anti-inflammatory, immunomodulatory and anti-tumor effects. However, its modulatory effects and action mechanisms on myeloid cells remain poorly understood. In this study, tryptanthrin was shown to suppress the proliferation of the murine myeloid leukemia WEHI-3B JCS cells in a dose- and time-dependent manner. It also significantly reduced the growth of WEHI-3B JCS cells in vivo in syngeneic BALB/c mice. However, it exhibited no significant direct cytotoxicity on normal murine peritoneal macrophages. Flow cytometric analysis showed an obvious cell cycle arrest of the tryptanthrin-treated WEHI-3B JCS cells at the G0/G1 phase. The expression of cyclin D2, D3, Cdk 2, 4 and 6 genes in WEHI-3B JCS cells was found to be down-regulated at 24 h as measured by RT-PCR. Morphological and functional studies revealed that tryptanthrin could induce differentiation in WEHI-3B JCS cells, as shown by the increases in vacuolation, cellular granularity and NBT-reducing activity in tryptanthrin-treated cells. Collectively, our findings suggest that tryptanthrin might exert its anti-tumor effect on the murine myelomonocytic leukemia WEHI-3B JCS cells by causing cell cycle arrest and by triggering cell differentiation.

Photodynamic therapy-mediated modulation of inflammatory cytokine production by Epstein–Barr virus-infected nasopharyngeal carcinoma cells

Nasopharyngeal carcinoma(NPC)is a malignant disease associated with Epstein–Barr virus(EBV)infection.This study aims to examine the effects of EBV infection on the production of proinflammatory cytokines in NPC cells after the Zn-BC-AM photodynamic therapy(PDT)treatment.Cells were treated with the photosensitiser Zn-BC-AM for 24 h before light irradiation.Quantitative ELISA was used to evaluate the production of cytokines.Under the same experimental condition,HK-1-EBV cells produced a higher basal level of IL-1a(1561 pg/ml),IL-1b(16.6 pg/ml)and IL-8(422.9 pg/ml)than the HK-1 cells.At the light dose of 0.25–0.5 J/cm2,Zn-BC-AM PDT-treated HK-1-EBV cells were found to produce a higher level of IL-1a and IL-1b than the HK-1 cells.The production of IL-1b appeared to be mediated via the IL-1b-converting enzyme(ICE)-independent pathway.In contrast,the production of angiogenic IL-8 was downregulated in both HK-1 and HK-1-EBV cells after Zn-BC-AM PDT.Our results suggest that Zn-BC-AM PDT might indirectly reduce tumour growth through the modulation of cytokine production.