Title:Natural Products as PI3K/ Akt Inhibitors: Implications in Preventing Hepatocellular Carcinoma
Volume: 14
Author(s): Arunaksharan Narayanankutty*
Affiliation:
- Division of Cell and Molecular Biology, PG and Research Department of Zoology, St. Joseph's College (Autonomous), Devagiri, Calicut, Kerala,India
Keywords:
Hepatocellular carcinoma, PI3K/Akt pathway, natural products, metastasis, drug resistance, apoptosis.
Abstract: Hepatocellular carcinoma (HCC) is one of the prominent forms of cancer in developed
countries. Globally, the incidence of HCC is well correlated with fatty liver disease and cirrhosis;
the underlying chronic inflammation and lipotoxicity are thought to drive the process of HCC. Several
biochemical cycles and molecular pathways are associated. The review aims to summarize the
role of PI3K/Akt signaling and its downstream effectors in the development of HCC and its progression.
Further, the emphasis has been given to the role of natural inhibitors of the PI3K/Akt
pathway in HCC prevention, which are under various levels of drug discovery. The required literature
were collected from PubMed/Medline databases, as well as Scopus or Web of science. It is evident
that various signaling pathways activated by growth factors together with detoxification
machinery and biochemical cycles converge to the PI3K/Akt signaling. The pathway plays a key
role in the carcinogenesis, metastasis and drug resistance events of HCC cells and provides the
growth and survival advantage. Natural products belonging to various classes such as terpenoids,
flavonoids, saponins and stilbenoids are proven inhibitors of PI3K signaling and also found to inhibit
HCC progression. PI3K/mTOR pathway inhibitors, especially the different phytochemicals,
emerged as promising as anti-HCC agents. These molecules are shown to interfere with the PI3K
signaling at various stages and therefore the PI3K targeted drugs may be a future for the chemotherapeutic
arena.
