Phytochemicals and PI3K Inhibitors in Cancer-An Insight

Abstract

In today's world of modern medicine and novel therapies, cancer still remains to be one of the prime contributor to the death of people worldwide. The modern therapies improve condition of cancer patients and are effective in early stages of cancer but the advanced metastasized stage of cancer remains untreatable. Also most of the cancer therapies are expensive and are associated with adverse side effects. Thus, considering the current status of cancer treatment there is scope to search for efficient therapies which are cost-effective and are associated with lesser and milder side effects. Phytochemicals have been utilized for many decades to prevent and cure various ailments and current evidences indicate use of phytochemicals as an effective treatment for cancer. Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling cascades is a common phenomenon in most types of cancers. Thus, natural substances targeting PI3K pathway can be of great therapeutic potential in the treatment of cancer patients. This chapter summarizes the updated research on plant-derived substances targeting PI3K pathway and the current status of their preclinical studies and clinical trials.

Keywords: 5-bisphosphate (PI3K); Mammalian TORC pathway; Mitogen-activated protein kinases (MAPK); cancer; clinical trials; phosphatidylinositol-4; phytochemicals.

Figure 1

Phytochemicals and their sources.

Figure 2

PI3K signaling pathway. Cytokine, growth factor (RKT), hormones and intergrins are prime extra-cellular signals, which tend to transmit via suited pathways to control various cellular processes, like autophagy, DNA repair, cell cycle, angiogenesis, motility, angiogenesis, and senescence. BAD, Bcl-2-associated death promoter; FOXO, Forkhead box protein O; GPCR, G protein coupled receptors; GSK3, Glycogen synthase kinase 3; JNK, c-Jun N-terminal kinases; LKB1, Liver kinase B1; MDM2, Mouse double minute 2 homolog; mTOR C1, Mammalian target of rapamycin complex 1; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; PDK1, Pyruvate dehydrogenase lipoamide kinase isozyme 1; PI3K, Phosphatidylinositide 3-kinases; PIP3, Phosphatidylinositol (3,4,5)-triphosphate; RHEB, Ras homolog enriched in brain; RTK, Receptor tyrosine kinase; TCS1/2, Two-component signal transduction protein 1/2.