Effects of an elemental diet, Elental®, may differ between healthy oral cells and oral cancer cells

Abstract

The effectiveness of an elemental diet (ED), Elental®, against radiotherapy- or chemoradiotherapy-induced oral mucositis was previously reported. However, the administration of additional nutrition or an ED in patients with oral cancer may also provide extra nutrition for cancer cells, which could result in cancer development. At present, it remains unclear whether the beneficial effects of an ED are likely to surpass its potential harmful effects on oral cancer treatment. In the present study, we aimed to clarify whether Elental® has different effects on a healthy human oral keratinocyte (HOK) cell line compared with its effects on oral squamous cell carcinoma (OSCC) cell lines (HSC2, HSC3, HSC4). The efficacy of Elental® was compared in relation to the growth and migration ability of HOK and OSCC cell lines using MTT assay and migration assay, respectively. In addition, whole transcriptome analysis and network analysis were performed to determine the difference in the mechanism of action of Elental® between HOK and HSC2 cells. In addition, Elental® promoted growth and migration ability of-malnourished and 5-fluorouracil (5-FU)-treated damaged HOK cells cultured in low nutrition medium (0% growth supplement). However, Elental® did not affect the growth ability of 5-FU-treated damaged HSC2 cell line in low nutrition medium (0 or 1% fetal bovine serum (FBS), as well as the growth ability of HSC3 and HSC4 cell lines in medium containing 0% FBS. Elental® pre-treatment also enhanced the apoptosis-inducing effect of anticancer agents against OSCC cells. In addition, whole transcriptome analysis and Ingenuity Pathways Analysis (IPA) data suggested that Elental® may help in the proliferation and survival of HOK through the induction of ERK. Moreover, Elental® added stress to HSC2 cells through the induction of the endoplasmic reticulum stress response marker, BiP and GRP 94. The results showed that Elental® may add stress to HSC2 cells and provide growth stimulation to HOK. These findings suggest that the effects of Elental® on healthy oral cells and oral cancer cells may differ.