Chemopreventive activity of Tualang honey against oral squamous cell carcinoma-in vivo.

OBJECTIVE: The aim of this study was to evaluate the chemopreventive activity of Malaysian jungle Tualang honey (TH) after oral carcinogenesis induced with 4-nitroquinoline 1-oxide (4 NQO). STUDY DESIGN: A total of 28 male Sprague-Dawley (SD) rats were distributed into 4 groups as follows: group 1 (nontreated group); group 2 (control), which received 4 NQO during 8 weeks in drinking water only; and groups 3 and 4, which received 4 NQO for 8 weeks in drinking water and treated with TH 1000 mg/kg and 2000 mg/kg by oral gavage for 10 weeks. All rats from all experiments were sacrificed after 22 weeks, and the incidence of oral neoplasms and histopathologic changes were microscopically evaluated. Moreover, immunohistochemical expression was analyzed in tongue specimens by using image analysis software. The expression of particular genes associated with oral cancer were assessed by using RT2 Profiler PCR Array (Qiagen, Germantown, MD). RESULTS: TH significantly reduced the incidence of oral squamous cell carcinoma (OSCC) and suppressed cancer cell proliferation via diminishing the expression of CCND1, EGFR, and COX-2. Furthermore, TH preserved cellular adhesion (epithelial polarity) through overexpression of ß-catenin and e-cadherin and inhibited the OSCC aggressiveness by downregulating TWIST1 and RAC1. CONCLUSIONS: Our data suggest that TH exerts chemopreventive activity in an animal model in which oral cancer was induced by using 4 NQO.

Antiproliferative and apoptotic activities of 8-prenylnaringenin against human colon cancer cells.

AIMS: The compound 8-prenylnaringenin (8-PN) is a prenylflavonoid that can be isolated from hops and beer and has anti-cancer properties against breast cancer. The aim of this study is to investigate the anti-proliferative and apoptotic activities of 8-PN against human colon cancer HCT-116 cells. MAIN METHODS: Colon cancer HCT-116 cells were treated with 8-PN and subjected to MTT and acridine orange/propidium iodide (AO/PI) staining to investigate the cytotoxicity of 8-PN. Arrest of the cells at different phases of cell cycle was monitored in the presence of 8-PN. Moreover, the apoptotic effects of 8-PN was assessed via annexin V and caspase activity assays and compared to the untreated cells. KEY FINDINGS: The findings showed that 8-PN revealed strong inhibitory effect against HCT-116 cells with an IC50 value of 23.83 ±â€¯2.9 µg/ml after 48 h. However, at similar concentrations and experimental time-points, the compound did not show cytotoxic effect to non-cancerous colon cells (CCD-41). Annexin-V assay indicates that 38.5% and 14.4% of HCT-116 cells had entered early and late stages of apoptosis, respectively after exposure of the cells to 8-PN for 48 h. Caspase activity assay illustrates that apoptosis is activated through both intrinsic and extrinsic pathways. Moreover, flow cytometry cell cycle results indicate that treatment with 8-PN significantly arrested the HCT-116 cells at G0/G1 phase. SIGNIFICANCE: These findings reveal that 8-PN has anti-proliferative activity against HCT-116 colon cancer cells via induction of intrinsic and extrinsic pathway-mediated apoptosis. Further investigations should be carried out to unravel the mechanistic pathways underlying these activities.

An Association Map on the Effect of Flavonoids on the Signaling Pathways in Colorectal Cancer.

Colorectal cancer (CRC) is the third most common type of cancer in the world, causing thousands of deaths annually. Although chemotherapy is known to be an effective treatment to combat colon cancer, it produces severe side effects. Natural products, on the other hand, appear to generate fewer side effects than do chemotherapeutic drugs. Flavonoids are polyphenolic compounds found in various fruits and vegetables known to possess antioxidant activities, and the literature shows that several of these flavonoids have anti-CRC propertiesFlavonoids are classified into five main subclasses: flavonols, flavanones, flavones, flavan-3-ols, and flavanonols. Of these subclasses, the flavanonols have a minimum effect against CRC, whereas the flavones play an important role. The main targets for the inhibitory effect of flavonoids on CRC signaling pathways are caspase; nuclear factor kappa B; mitogen-activated protein kinase/p38; matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9; p53; ß-catenin; cyclin-dependent kinase (CDK)2 and CDK4; and cyclins A, B, D, and E. In this review article, we summarize the in vitro and in vivo studies that have been performed since 2000 on the anti-CRC properties of flavonoids. We also describe the signaling pathways affected by flavonoids that have been found to be involved in CRC. Some flavonoids have the potential to be an effective alternative to chemotherapeutic drugs in the treatment of colon cancer; well-controlled clinical studies should, however, be conducted to support this proposal.