6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model

Abstract

Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.

Metabolite mapping by consecutive nanostructure and silver‐assisted mass spectrometry imaging on tissue sections

“…6‐Bromoisatin is actively processed to yield several metabolites, including the dimer 6,6'‐dibromoindirubin (6,6'‐DBI), a known constituent of Tyrian purple ( m/z 419, Table ). Mice were administered a daily oral gavage with 6‐bromoisatin across a 14‐week model and tissues were excised 4 h after the last treatment . Sections were obtained from the fore‐stomach of a treated mouse and mounted onto a DIOS substrate to allow adsorptive transfer (imprinting) of analytes prior to physical removal of the section by rinsing and DIOS/Ag‐DIOS MSI.…”

Marine Mollusks: Food with Benefits

“…Inhibition of PGE2, TNFα, nuclear factor kappa B (NFκB), and NO was successfully achieved in latest experimental works when egg mass and hypobranchial glands of Dicathais orbita (Australian Muricidae) were applied in combination with Tyrian purple's brominated indole precursors (Ahmad et al., ). Similarly, the potency of 6‐bromoisatin (oxidation product), a biologically available multifunctional chemical agent of paramount importance, has been effectively and safely demonstrated in animal models with regard to avoidance of colon cancer (Benkendorff et al., ; Esmaeelian, Abbott, Le Leu, & Benkendorff, ). This bioactive agent was recently also found to be effective in the prevention of acute lung inflammation when tested in a mouse model (Ahmad et al., ).…”

Comparative study of the cytotoxic properties of isatin-containing derivatives of 4-thiazolidinone with different structure toward human tumor cells in vitro

“…Ізатин також має власну токсичну активність щодо злоякісних клітин. З'ясовано, що в кон-центрації 100 мкМ ізатин на 80 % пригнічує проліферацію клітин лінії HL-60 про-мієлоцитарного лейкозу людини, викликаючи їхню загибель шляхом апоптозу, а у концентрації 50 мкМ він індукує апоптоз клітин лінії SH-SY5Y нейробластоми лю-дини [2]. В іншому дослідженні встановлено, що похідне ізатину 2-феніліндолсуль-фамат є інгібітором стероїдної сульфатази, що перешкоджає проліферації клітин карциноми молочної залози людини [12].…”