Selective apoptotic effect of Zelkova serrata twig extract on mouth epidermoid carcinoma through p53 activation

Apoptosis or programmed cell death plays an essential role in chemotherapy-induced tumor cell killing, and inducers of apoptosis are commonly used in cancer therapy. Treatment with Zelkova serrata extracts was performed in human gingival fibroblast (HGF), mouth epidermoid carcinoma cell (KB), lower gingival squamous cancer cell (YD38) and tongue mucoepidermoid carcinoma cells (YD15). We observed that extract prepared from Zelkova serrata twig selectively inhibited proliferation of various oral cancer cells, but not normal gingival fibroblasts, in a dose-dependent manner. Caspase-8-mediated apoptosis was induced by treatment with the extract only in mouth epidermoid carcinoma and not in other types of cancer cells, including lower gingival squamous cell carcinoma. The selective apoptotic effect of Zelkova serrata twig extract in mouth epidermoid carcinoma was dependent on normal p53 status. Apoptosis was not remarkably induced by treatment with the extract in either lower gingival squamous or tongue mucoepidermoid carcinoma cells, both of which contain abnormalities of p53. Upon treatment with Zelkova serrata twig extract, mouth epidermoid carcinoma cells accumulated in S phase by activation of p21. These data indicate that Zelkova serrata twig extract exerted a cancer type-specific, p53-dependent apoptotic effect and disturbed the cell cycle, which suggests that herbal medicine could be a treatment for specific types of cancers. Extracts of Zelkova serrata, an East Asian plant used for food and medicinal purposes, contain compounds that may prove useful in treating some oral cancers. The prognosis for patients with such tumors is fairly poor: they have a five-year survival rate of around 50%. Since Z. serrata has proven useful for treating other medical conditions, Hoe-Jin Kang and Young-Joo Jang of Dankook University, Korea, tested whether extracts derived from twigs of this plant might have an effect on the growth of cell lines derived from different types of oral cancer. The researchers obtained one extract that proved specifically toxic to epidermoid carcinoma cells, triggering a cellular suicide mechanism that thwarts tumor growth. Further analysis of the molecules within this fraction may offer useful leads for future oral cancer drug development.