Britanin - a beacon of hope against gastrointestinal tumors?

Abstract

Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties. It also exhibits significant anti-tumor activity, suppressing tumor growth in vitro and in vivo. The current body of research on Britanin includes thirty papers predominantly related to neoplasms, the majority of which are gastrointestinal tumors that have not been summarized before. To drive academic debate, the present paper reviews the available research on Britanin in gastrointestinal tumors. It also outlines novel research directions using data not directly concerned with the digestive system, but which could be adopted in future gastrointestinal research. Britanin was found to counteract liver, colorectal, pancreatic, and gastric tumors, by regulating proliferation, apoptosis, autophagy, immune response, migration, and angiogenesis. As confirmed in pancreatic, gastric, and liver cancer, its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation, as well as Bcl-2-associated X protein upregulation. Moreover, it has been found to induce the Akt kinase and Forkhead box O1 axis, activate the AMP-activated protein kinase pathway, elevate interleukin-2 and peroxisome proliferator-activated receptor-γ levels, reduce interleukin-10, as well as downregulate matrix metalloproteinase-9, Twist family bHLH transcription factor 1, and cyclooxygenase-2. It also inhibits Myc-HIF1α interaction and programmed death ligand 1 transcription by interrupting the Ras/ RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling. Future research should aim to unravel the link between Britanin and acetylcholinesterase, mast cells, osteolysis, and ischemia, as compelling data have been provided by studies outside the gastrointestinal context. Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells, while still being effective against the latter, further in-depth studies with the use of animal models are merited. The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent, which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.

Keywords: Britanin; Chemotherapeutics; Gastrointestinal tumors; In vitro; In vivo; Sesquiterpene lactones.

Figure 1

Influence of Britanin on biological processes and related proteins in gastrointestinal tumors. A red upward pointing arrow (“↑”) indicates biological process activation by Britanin, whereas a blue downward pointing arrow (“↓“) signifies biological process inhibition by the same compound. Similar applies to the level of proteins, the symbols of which are located in four multicolored areas representing liver, colorectal, pancreatic, and gastric cancer cells.

Figure 2

Novel research directions which could be adopted in future gastrointestinal research on Britanin. The light-yellow rectangles represent data on Britanin obtained from studies other than those associated with liver, colorectal, pancreatic, and gastric cancer. Processes included therein are linked to various tumor-related phenomena, which are depicted in gray rectangles. Britanin was not yet investigated in these tumor-related phenomena, which was marked with solid red arrows and question marks (“?”). Such information may suggest the direction of further research on gastrointestinal tumors.