Helioxanthin suppresses the cross talk of COX-2/PGE2 and EGFR/ERK pathway to inhibit Arecoline-induced Oral Cancer Cell (T28) proliferation and blocks tumor growth in xenografted nude mice

Abstract

Helioxanthin, an active compound from Taiwania cryptomerioides Hayata, has been shown to have various biological activities. However, their anticancer effect in oral squamous cell carcinoma has not been well established yet. Helioxanthin inhibited the proliferation of oral squamous cell carcinoma cells in a dose-dependent manner by inducing G2/M phase arrest. Similarly, helioxanthin inhibited cyclooxygenase-2, (COX-2), phosphorylated EGFR, and extracellular-signal-regulated kinases (ERK) protein level and further reduced the nuclear accumulation of phosphorylated epidermal growth factor receptor (pEGFR) and activator protein-1(AP-1) family protein, c-fos. Moreover, helioxanthin at the dose of 20 and 30 mg kg for 15 days reduced the tumor growth in animal model. This study demonstrated that Helioxanthin exerts its anticancer activity against oral cancer cells by downregulating EGFR/ERK/c-fos signaling pathway to inhibit COX-2 level and by activating cyclin-dependent kinase inhibitor (p27) to further induce G2/M cell cycle arrest. This helioxanthin may serve as a novel candidate for oral cancer prevention. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2045-2056, 2016.

Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth

“…However, arecoline has also been associated with the development of oral premalignant lesions and risk of oral cancer in many areas of Asia, the Pacific region, and in migrant communities in the United Kingdom, United States and South Africa where betel chewing is prevalent (Gupta and Warnakulasuriya, 2002; Sharan et al, 2012). Several animal studies have shown that arecoline administered by oral gavage to male mice induced lung adenocarcinoma and liver hemangioma (Bhide et al, 1984; Bhide et al, 1979), and chronic oral administration of arecoline through drinking water resulted in oral squamous cell carcinoma in mice (Lin et al, 2015b). However, arecoline was found not mitogenic to oral mucosal fibroblasts, and it causes cell cycle arrest of cultured oral KB epithelial cells (Chang et al, 2001; Tsai et al, 1997).…”

Resveratrol inhibits the proliferation of A549 cells by inhibiting the expression of <em>COX-2</em>

“…16 Another study suggested that the mechanism of overexpressed COX-2 in promoting the proliferation of tumor cells is due to the role of Polygalacturonases (PGs), a product of COX-2 protein metabolism, especially PGE2, which enhances the proliferation of tumor cells. 30 The increase of PGE2 will not only inhibit the increase of T lymphocytes or B lymphocytes, but also induce the production of immunosuppressive cytokine IL-10. 31 Therefore, the body’s immune surveillance function is decreased, thereby increasing the probability of tumor cells proliferation.…”

Excavatolide B inhibits nonsmall cell lung cancer proliferation by altering peroxisome proliferator activated receptor gamma expression and PTEN/AKT/NF‐Kβ expression

“…Cell viability was determined as mentioned previously by (Lin et al, ). NSCLC cells—A549, H520, and H661 cells (1 × 10 4 cells per well) and normal human bronchial epithelium cells ‐BEAS‐2B (5 × 10 3 cells per well) were seeded in 96‐well plate (Corning, NY).…”