New options of cancer treatment employing InsP6

Abstract

Many mechanistic studies have been performed to analyze the cellular functions of the highly phosphorylated molecule inositol hexakisphosphate (InsP₆) in health and disease. While the physiological intracellular functions are well described, the mechanism of potential pharmacological effects on cancer cell proliferation is still controversial. There are numerous studies demonstrating that a high InsP₆ concentration (≥75 µM) inhibits growth of cancer cells in vitro and in vivo. Thus, there is no doubt that InsP₆ exhibits anticancer activity but the mechanism underlying the cellular effects of extracellular InsP₆ on cancer cells is far from being understood. In addition, studies on the inhibitory effect of InsP₆ on cancer progression in animal models ignore aspects of its bioavailability. Here, we review and critically discuss the uptake mechanism and the intracellular involvement in signaling pathways of InsP₆ in cancer cells. We take into account the controversial findings on InsP₆ plasma concentration, which is a critical aspect of pharmacological accessibility of InsP₆ for cancer treatment. Further, we discuss novel findings with respect to the effect of InsP₆ on normal and immune cells as well as on platelet aggregate size. Our goal is to stimulate further mechanistic studies into novel directions considering previously disregarded aspects of InsP₆. Only when we fully understand the mechanism underlying the anticancer activity of InsP₆ novel and more efficient treatment options can be developed.

Keywords: Cancer treatment; Inositol hexakisphosphate; Platelets; Tumor.