Taiwanin C elicits apoptosis in arecoline and 4-nitroquinoline-1-oxide-induced oral squamous cell carcinoma cells and hinders proliferation via epidermal growth factor receptor/PI3K suppression

Environ Toxicol. 2019 Jun;34(6):760-767. doi: 10.1002/tox.22742. Epub 2019 Mar 18.

Abstract

Oral Squamous Cell Carcinoma (OSSC) is a major life-threatening disease with high incidence in the Southeast Asian countries. Chronic exposure to arecoline causes genetic changes in the epithelial cells of the oral mucosa, induces proliferation through activation of the EGF receptor and promotes downstream COX-2 expression. Taiwanin C, a podophyllotoxin derived from Taiwania cryptomerioides Hayata is known to inhibit COX activity and to hinder PGE2 production in macrophages. In this study a tumor cell line T28 and a non-tumor cell line N28 derived from mice OSCC models were used to study the effect of Taiwanin C on PGE2 associated COX-2 expression and cell cycle regulators. Taiwanin C activated p21 protein expression, down-regulated cell cycle regulatory proteins, elevated apoptosis and down-regulated p-PI3K/p-Akt survival mechanism in T28 oral cancer cells. Our results therefore emphasize the therapeutic potential of Taiwanin C against arecoline-induced oral cancer.

Keywords: Taiwania cryptomerioides; Taiwanin C; anticancer; cell cycle; cytotoxicity; oral cancer.

MeSH terms

  • 4-Nitroquinoline-1-oxide / toxicity
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Arecoline / toxicity
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Lactones / pharmacology*
  • Lignans / pharmacology*
  • Male
  • Mice, Inbred C57BL
  • Mouth Neoplasms / chemically induced
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Phosphoinositide-3 Kinase Inhibitors*

Substances

  • Antineoplastic Agents, Phytogenic
  • Lactones
  • Lignans
  • Phosphoinositide-3 Kinase Inhibitors
  • taiwanin C
  • Arecoline
  • 4-Nitroquinoline-1-oxide
  • ErbB Receptors