New options of cancer treatment employing InsP6

TY - JOUR

T1 - New options of cancer treatment employing InsP6

AU - Brehm, Maria A

AU - Windhorst, Sabine

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/5

Y1 - 2019/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.bcp.2019.02.024

DO - 10.1016/j.bcp.2019.02.024

M3 - SCORING: Review article

C2 - 30797871

VL - 163

SP - 206

EP - 214

JO - BIOCHEM PHARMACOL

JF - BIOCHEM PHARMACOL

SN - 0006-2952

ER -