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

Abstract

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-

Biologically active quinoline and quinazoline alkaloids part II

“…Meanwhile, tryptanthrin induced differentiation in the same cells by increasing vacuolation, cellular granularity, and NBT‐reducing activity. Thus, tryptanthrin exerts an antitumor effect on WEHI‐3B JCS (myelomonocytic leukemia) cells by causing cell cycle arrest and triggering cell differentiation in a dose‐ and time‐dependent manner …”

Quercetin and Tryptanthrin

“…Its efficacy against allergy [87], intestinal disorders [88], and inflammatory bowel disease [89] has also been reported. More interestingly, the cytotoxic [57,69,[90][91], antitumor [92][93][94], and chemopreventive [95] potential of this indoloquinazoline alkaloid has also been illustrated by many researchers [96]. Various biological and pharmacological properties of tryptanthrin are depicted in Fig.…”

“…Its low concentrations induce differentiation of monocytic and promyelocytic leukemia cells (U-937 and HL-60), while the higher concentrations induce apoptosis through caspase-3/Fas antigen pathway [92]. Tryptanthrin is also able to exert both in vitro as well as in vivo antitumor effect toward the murine myelomonocytic leukemia cell, WEHI-3B JCS through the induction of cell cycle arrest as well as by triggering cell differentiation [94]. It also induces apoptosis in K562 leukemic cells by the reduction in mitochondrial membrane potential resulting in release of cytochrome c from mitochondria and subsequently, the activation of procaspase-3 [99].…”

Benzo[b]tryptanthrin Inhibits MDR1, Topoisomerase Activity, and Reverses Adriamycin Resistance in Breast Cancer Cells

“…[7] Tryptanthrin also showed antitumoral activity by targeting indoleamine 2,3-dioxygenase (IDO-1), and 8-fluorotryptanthrin, a stronger IDO-1 inhibitor than tryptanthrin, potently suppressed tumor growth in Lewis lung cancer tumor-bearing mice. [8] Potent cytocidal effects of tryptanthrin on various human leukemia cells [9,10] and on azoxymethane-induced intestinal tumors have been reported. [11] In addition, antifungal, antimicrobial, tuberculostatic, COX-2 inhibitory, 5-LOX inhibitory, nitric oxide (NO) synthase inhibitory, and antimalarial activities of tryptanthrin have been reported.…”

“…[16] Among the numerous reported biological and pharmacological activities of tryptanthrin, no inhibitory activity against topoisomerases (topos) was reported, and some cytocidal anticancer activities of tryptanthrin have been stated without clear explanation of the target. [9][10][11]13] Topos are essential enzymes for solving DNA topological problems encountered during DNA transcription, replication, recombination, and chromosome segregation in mitosis following replication. Human topos are grouped into two types, Tryptanthrin is an indoloquinazoline alkaloid isolated from indigo.…”