Inositol hexaphosphate (IP6) and breast cancer: efficacy, mechanisms, and clinical application

Abstract

Despite our increasingly broader understanding of the risk factors and introduction of newer anticancer drugs, breast cancer is still the most prevalent malignancy in women worldwide. Because most of the currently used chemotherapeutic agents do not discriminate between normal and tumor cells, resulting in unacceptable side-effects, there is an urgent need for drugs that specifically attack tumor cells, while sparing the normal.

Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate, naturally occurring in plants and virtually all mammalian cells, with a broad spectrum of anticancer action with remarkable efficacy against divergent types of cancers, including those of breast. The observed anticancer activity was potentiated in vivo by myo-inositol (Ins), its parent compound. IP6 reduces cell proliferation, induces differentiation of malignant cells, restores immune system, controls cancer metastases and acts synergistically with conventional chemotherapy to yield a better quality of life at the minimum.

In mechanistic studies, IP6 exposure resulted in significant induction of p27Kip1, and marked reduction of pRb phosphorylation. IP6 has been shown to affect various signaling pathways, such as PI3-K/AKT, MAPK/ERK, and PKC, by inhibiting the survival/pro-proliferative and stimulating the anti-proliferative and pro-apoptotic molecules; it appears that this action is mediated by PKC ?. Additionally, IP6 causes a time- and dose-dependent apoptotic death, and PKC ? seems to be an important mediator in IP6-induced apoptosis of breast cancer cells as well.