Tryptanthrin information and scientific trials, possible use for cancer

Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses.

Several substances in woad have anti-inflammatory activity. One such substance is tryptanthrin, a known dual inhibitor of cyclooxygenase-2 (COX-2) and 5-LOX. Tryptanthrin is a pharmacologically active compound with potent inhibitory activity on prostaglandin and leukotriene synthesis and on inducible nitric oxide synthase.

Tryptanthrin for Toxoplasma gondii infections
Inhibition of Toxoplasma gondii by indirubin and tryptanthrin analogs.
Antimicrob Agents Chemother. 2008; Krivogorsky B, Grundt P, Jones-Brando L. Dept. of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD, USA.
New drugs are needed for treatment of Toxoplasma gondii infections. We tested derivatives of principles found in Isatis indigotica for in vitro efficacy against T. gondii infection. Indirubin-3'-oxime analogs showed modest micromolar activity, while tryptanthrin derivatives displayed 50% inhibitory doses in the low nanomolar range. Tryptanthrins have potential as anti-Toxoplasma infection therapeutics.

Tryptanthrin as a chemotherapy medication
Tryptanthrin inhibits MDR1 and reverses doxorubicin resistance in breast cancer cells.
Biochem Biophys Res Commun. 2007.  Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
Development of agents to overcome multidrug resistance is important in cancer chemotherapy. Up to date, few chemicals have been reported to down-regulate MDR1 gene expression. We evaluated the effect of tryptanthrin on P-glycoprotein (P-gp)-mediated multidrug resistance in a breast cancer cell line MCF-7. Tryptanthrin depressed overexpression of MDR1 gene. We observed reduction of P-gp protein in parallel with decreases in mRNA in MCF-7/adr cells treated with tryptanthrin. Tryptanthrin suppressed the activity of MDR1 gene promoter. Tryptanthrin also enhanced interaction of the nuclear proteins with the negatively regulatory CAAT region of MDR1 gene promoter in MCF-7/adr. It might result in suppression of MDR1 gene. In addition, tryptanthrin decreased the amount of mutant p53 protein with decreasing mutant p53 protein stability. In conclusion, tryptanthrin exhibited MDR reversing effect by down-regulation of MDR1 gene and might be a new adjuvant agent for chemotherapy.

Leukemia
Modulatory effects and action mechanisms of tryptanthrin on murine myeloid leukemia cells.
Cell Mol Immunol. 2009 Oct; Department of Biochemistry, The Chinese University of Hong Kong, Shatin, HKSAR, China.
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.

Tryptophan serotonin home