Lycopene inhibits growth of human colon cancer cells via suppression of the Akt signaling pathway

Abstract

The aberrant regulation of the phosphoinositide 3-kinase/Akt survival signaling pathway in cancer has prompted significant interest in suppression of this pathway to treat cancer. Previous studies identified an important role for phosphoinositide 3-kinase/Akt in colon cancer progression. Lycopene, a major component in tomato, exhibited potential anti-carcinogenic activity. Consumption of tomato has been associated with reduced risk of several types of human cancer. However, the inhibitory mechanisms of lycopene on the proliferation of human colon cancer have not been studied well yet. Thus we investigated the inhibitory effects of lycopene on the Akt signaling pathway in human colon cancer HT-29 cells. Lycopene inhibited cell proliferation in human colon cancer HT-29 cells with a IC(50) value of 10 microM. Lycopene treatment suppressed Akt activation and non-phosphorylated beta-catenin protein level in human colon cancer cells. Immunocytochemical results indicated that lycopene increased the phosphorylated form of beta-catenin proteins. These effects were also associated with reduced promoter activity and protein expression of cyclin D1. Furthermore, lycopene significantly increased nuclear cyclin-dependent kinase inhibitor p27(kip)abundance and inhibited phosphorylation of the retinoblastoma tumor suppressor protein in human colon cancer cells. In conclusion, lycopene inhibited cell proliferation of human colon cancer cells via suppression of the Akt signaling pathway and downstream targeted molecules.

Antiproliferative effect of oleuropein in prostate cell lines

“…Therefore, oleuropein can induce apoptosis through the downregulation of pAkt, suggesting an inhibitory effect on Akt signaling. These results are consistent with previous studies showing that natural antioxidants could induce apoptosis through the regulation of Akt (64). As with other natural agents which target multiple pathways, oleuropein treatment could be useful both for the prevention of tumour progression and/or therapy, either alone or in combination with conventional preventive or therapeutic agents for the prevention and/or treatment of prostate cancer.…”

Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene

“…48 Also, K-Ras was shown to activate the P13k/ Akt transduction route, 49 with the mutation of K-Ras and P13K accounting for 22% in colorectal cancer. 50 A similar outcome was observed by Tang et al 30 who demonstrated that LP was not only effective at suppressing Akt activation and nonphosphorylated β-catenin levels in colon cancer cell line, HT-29, but that it also enhanced the phosphorylation level of β-catenin leading to proteosomal degradation through the downregulation of the Wntl/β-catenin pathway. Similarly, Lin et al 51 illustrated that LP could not only enhance the expression and stability of E-cadherin, but it also inhibited the phosphorylation of Akt and the expression of MMP-7, a MMP modulated by extracellular growth factors and proinflammatory cytokines in cancer cells for degradation of the extracellular matrix and creation of a microenvironment to promote tumor angiogenensis and metastasis.…”

“…Obviously, with the high-dose (12 µM) treatment of LP, the proportion of HT-29 cells undergoing late apoptosis or necrosis was higher than early apoptosis. However, a slightly higher inhibition effect was reported by Tang et al 30 as a 47% suppression of the HT-29 cells was observed after 24 hours of incubation with the 10 µM LP standard. The difference in antiproliferation effect may be accounted for by the source of LP used in cell culture (ie, in our experiment, LP paste from tomato was used as the raw material, while in Tang et al's study, 30 LP standard was employed).…”

“…However, a slightly higher inhibition effect was reported by Tang et al 30 as a 47% suppression of the HT-29 cells was observed after 24 hours of incubation with the 10 µM LP standard. The difference in antiproliferation effect may be accounted for by the source of LP used in cell culture (ie, in our experiment, LP paste from tomato was used as the raw material, while in Tang et al's study, 30 LP standard was employed). Also, in a similar study, LP was shown to suppress leptin-mediated cell invasion and MMP-7 expression in HT-29 cells, even at physiological concentrations ranging from 0.5 µM to 2 µM.…”

Functional and Morphological Studies of Organic and Inorganic Tomatoes

“…1,2 Recent epidemiological studies have suggested that the consumption of tomatoes and tomato-based food products helps in reducing the risk of cardiovascular disease and cancer (oral cavity, pharynx, esophagus, stomach, rectum, colon, urinary bladder, prostate and breast) in humans as reported by, 3,4,5 and this protective effect has been attributed to carotenoids, in particular lycopene and phenolic compounds which are considered as one of the major classes of phytochemicals in this fruit. 6 As we know carotenoids are a family of compounds of over 600 fat-soluble plant pigments that provide much of the color we see in nature, by facilitating important nutritional benefits to human population owing to their pro vitamin A and antioxidant activities.…”