Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via PI3K/Akt pathway

Abstract

Cervical cancer (CC) is a malignant neoplasm arising from cells originating in the cervix uteri, among the top causes of death from cancer in women. In a gene expression profiling study of metabolic response to treatment, PI3K/Akt signaling pathway are associated with the development of CC. A common mechanism of Akt activation seen in cancer types is alterations in the upstream regulators of Akt such as phosphatidylinositol 3-kinase (PI3K), which is overexpressed in cervical cancer tissues, and leads to phosphorylation of Akt. Both PI3K and Akt inhibitors exist and may be therapeutically valuable. In the present study, we use MTT assay and western blot for the high-throughput screening to select specific inhibitors of PI3K/Akt signaling pathway, and then obtain fucoxanthin. Fucoxanthin is a water-soluble dietary fiber, taken from the unique slimy component of alginic cells. Various studies have pointed out that fucoxanthin is very effective for the treatment of cancer. Our results have shown that fucoxanthin induced a significant apoptosis of HeLa cells, compared with other candidates. After treatment with fucoxanthin for 24 h, the level of phosphorylation was inhibited in a dose-dependent manner, and the proteins of apoptotic markers were changed in HeLa cells. And fucoxanthin could suppress tumor growth in vivo. In addition, the mitochondrial signal transduction pathway maybe was involved in its mechanism and NF-κB activation was decreased after treatment with fucoxanthin. Therefore, fucoxanthin may be used as anti-cervical cancer drugs in the future.

Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling

“…These results demonstrate that CrkL may promote cervical cancer cell invasion through activation of Src signaling pathways. In addition, CrkL was also found to promote Akt phosphorylation; Akt signaling activation has been reported to be involved in the chemoresistance of cancer cells through antiapoptotic proteins such as Bcl-2 and Bcl-xL (36,37). Thus it is possible that CrkL increases cervical cancer chemoresistance through activating Akt signaling.…”

Antitumor and Cancer-preventative Function of Fucoxanthin: A Marine Carotenoid

“…Ganesan et al showed that 10 μM of fucoxanthin caused apoptosis and caspase-3 activation in HL-60 cells (29). Fucoxanthin (0.5 μM) was shown to induce caspase-dependent apoptosis with an increase in BAX and reduction in BCL2, phosphatidylinositol-3-kinase (PI3K) and a phosphorylated form of AKT in HeLa cells (30). The authors also found NF-ĸB inactivation and a decrease in its translocation to the nucleus from the cytoplasm in cells treated with fucoxanthin.…”

A comparative analysis of fatty acid composition and fucoxanthin content in six Phaeodactylum tricornutum strains from diff erent origins

“…Interestingly, fucoxanthin and its metabolite fucoxanthinol exhibit few adverse effects on normal, uninfected cells both in vitro and in vivo (Yamamoto et al, 2011). Extensive studies have been carried out regarding the separation, purifi cation, bioavailability, and biological activity of fucoxanthin from macroalgae (Wang et al, 2005;Yang et al, 2008;Fung et al, 2013;Molina et al, 2014;Ye et al, 2014). However, the fucoxanthin content in macroalgae is very low, requiring complex processes for purifi cation and high production costs.…”