Fucoxanthin and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Synergistically Promotes Apoptosis of Human Cervical Cancer Cells by Targeting PI3K/Akt/NF-κB Signaling Pathway

BACKGROUND: Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively induces apoptosis in many tumor cells and is an attractive candidate for antitumor therapies. MATERIAL/METHODS: After human cervical cancer cell lines HeLa, SiHa, and CaSki were treated with fucoxanthin or TRAIL. Cell viability was determined by 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2-tetrazolium 5-carboxanilide (XTT) method. Apoptosis was measured by flow cytometry (FCM). Protein expression of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), phosphated Akt (p-Akt), NF-κB nuclear factor-k-gene binding (NF-κB). Phosphated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (p-IκBa), was measured by Western blot analysis. mRNA expression of Bax and Bcl2 was measured by RNA preparation and quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In the present study, the effectiveness in terms of apoptosis was as follows: TRAIL plus fucoxanthin>fucoxanthin>TRAIL, indicating the combination of fucoxanthin and TRAIL, produced a strong synergistic effect on apoptosis in human cervical cancer cells. Additionally, we found that upstream signaling PI3K/Akt and NF-κB pathways-mediated cell apoptosis was activated by TRAIL and suppressed by fucoxanthin. By using PI3K and NF-κB inhibitors LY49002 and PDTC, we found that fucoxanthin- or TRAIL-induced apoptosis of human cervical cancer cells was obviously down-regulated. CONCLUSIONS: Taken together, these findings suggest that fucoxanthin and TRAIL increased the apoptosis in human cervical cancer cells by targeting the PI3K/Akt/NF-κB signaling pathway.