Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy

Abstract

The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been used since 1972 to treat malignant tumors of the head and neck at Kyushu University. Using nick end labeling of tumor specimens, cells of human maxillary sinus carcinomas were observed previously to undergo apoptosis in response to FAR therapy. The present study evaluated the in vitro effects of FAR therapy on a human maxillary sinus cancer (IMC-4) cell line. We further compared the effects of FAR therapy on this cell line with those effects seen on tissue samples taken from patients with maxillary sinus cancers. DNA electrophoresis and electron microscopic examination of the IMC-4 cells after treatment with FAR therapy revealed typical apoptotic features. The effects of 50-100 micrograms/ml 5-FU, 10(-4) M all-trans-retinoic acid and radiation to 6 Gy on IMC-4 cells were evaluated by trypan blue dye exclusion and a cell colony formation assay. 5-FU and radiation caused direct cell death, while vitamin A mainly inhibited cell growth. The combination of these treatment as FAR therapy synergistically enhanced cell death and inhibited cell growth. Flow cytometry demonstrated that FAR-treated cells were arrested in the G1 phase of the cell cycle before undergoing apoptosis. To further investigate possible biological parameters influencing a tumor's apoptotic sensitivity, we also examined the expression of p53 in human maxillary sinus cancer cells and analyzed the relationship between p53 expression and apoptosis. However, no relationship was found between these two markers at the time point studied.

All‐trans‐retinoic Acid Enhances the Effect of Adenovirus‐Mediated Wild‐Type p53 Gene Transfer in Head and Neck Squamous Cell Carcinoma

“…This incubation time was determined from previous time course growth assays. 20 Proliferation assays of the cells were performed by direct cell count using a Coulter counter (Coulter Corp., Miami, FL).…”

The Roles of JNK1 and Stat3 in the Response of Head and Neck Cancer Cell Lines to Combined Treatment with All trans‐retinoic Acid and 5‐Fluorouracil

“…4A and 6), and the synergistic effects of ATRA, 5-FU and γ-radiation on induction of apoptosis seen in our previous study. 12) Thus, additive or synergistic effects between these agents with respect to JNK1 activation may be relevant to the clinical efficacy of FAR therapy in the treatment of HNSCC.…”

“…12) However, the precise mechanism by which ATRA, 5-FU and radia-E-mail: masuda@cuccfa.ccc.columbia.edu The abbreviations used are: 5-FU, 5-fluorouracil; ATRA, alltrans-retinoic acid; RA, retinoic acid; RAR, retinoic acid receptor; HNSCC, head and neck squamous cell carcinoma; cdk, cyclin-dependent kinase; pRB, retinoblastoma protein; Stat3, signal transducer and activator of transcription 3; JNK, c-Jun N-terminal kinase; EGFR, epidermal growth factor receptor; TGF-α, transforming growth factor-α; PBS, phosphate-buffered saline; SDS, sodium dodecyl sulfate; PVDF, polyvinylidene difluoride; HA, hemaggultinin peptide; SIE, sis-inducible element.…”

Correlation between expression of cellular retinol-binding protein 1 and its methylation status in larynx cancer

“…These findings could be extended to good response to classic chemotherapy scheme (eg, 5-fluorouracil, etc). It has been reported that retinol may promote fluorouracil-suppressed healing of experimental intestinal anastomoses,20 induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation therapy,21 or promotion of apoptosis through an increase in all-trans retinoic acid synthesis 22. Further, the function of the CRBP1 gene in controlling the availability of vitamin A to cells suggests that its product has a special relevance to inhibition of transformation.…”