M.W. Roomi, N.W. Roomi, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050

Presented at: 
26th Annual Fanconi Anemia Research Fund Symposium, September 18-21, 2014, Bethesda, MD

Published in: 
Proceedings of the 26th Annual Fanconi Anemia Research Fund Scientific Symposium, page 61.

Abstract

Objective: Fanconi anemia (FA) is an autosomal recessive disease characterized by bone marrow failure, congenital abnormalities, chromosomal instability and cancer predisposition. Head and neck squamous cell carcinoma (HNSCC) and acute myeloid leukemia are the major causes of mortality and morbidity in FA patients. The objective of this study was to investigate the antineoplastic activity of a specific nutrient mixture (PB) of quercetin, curcumin, green tea, cruciferex and resveratrol on OHSU-974 human cell line FAHSCC in vivo and vitro.

Method and Materials: Human FAHNSCC cell line OHSU-974 (Fanconi Anemia Research Fund, Oregon Health & Science University, Portland, Oregon, USA) was cultured in RPMI medium supplemented with 20% FBS and antibiotics. At near confluence, cells were treated in triplicate with PB: 0, 10, 25, 50, 75 and 100 µg/ml concentrations. Cells were also treated with PMA to induce MMP-9 activity. Cell proliferation was detected by MTT assay, secretion of MMPs by gelatinase zymography, invasion through Matrigel and morphology by H&E staining. In vivo, athymic male mice (n=12) were inoculated with three million OHSU-974 cells subcutaneously and randomly divided into two groups: group A was fed a regular diet and group B the same diet supplemented with 1% PB. Four weeks later, the mice were sacrificed and their tumors were excised, weighed and processed for histology.

Results: PB inhibited the growth of OHSU-974 tumor by 65% and tumor burden by 62%. PB inhibited the growth of OHSU-974 cells by 10%, 25% and 50% at 50, 75 and 100 µg/ml concentrations in vitro. Zymography exhibited MMP-2 and PMA induced MMP-9 secretion. PB suppressed the expression of both MMPs at 10 and 25 µg/ml , with total abolition at 50 µg/ml. PB inhibited OHSU-974 invasion through Matrigel in a dose response fashion with total block at 75 µg/ml. H&E staining showed no morphological changes below 50 µg/ml.

Conclusions: The results suggest that PB has potential therapeutic use in the treatment of human FA HNSCC.

Translational Applicability: Current treatments for FA associated cancers are generally ineffective. Thus there is need for development of effective therapeutic agents with minimal toxicity. Our results suggest that PB significantly inhibited the growth of FA HNSCC cell line OHSU-974 in vivo. Furthermore, invasive parameters, such MMPs secretion and invasion through Matrigel were significantly effective. These findings suggest potential of PB in treatment of FA related HNSCC.

Comments

Head and neck squamous cell carcinoma (HNSCC) and acute myeloid leukemia are the major causes of mortality and morbidity in Fanconi anemia patients. Current treatments for FA associated cancers are generally ineffective. Thus there is need for development of effective therapeutic agents with minimal toxicity. The objective of this study was to investigate the antineoplastic activity of a specific nutrient mixture (PB) of quercetin, curcumin, green tea, cruciferex and resveratrol on OHSU-974 human cell line FAHSCC in vivo and vitro. Our results suggest that PB significantly inhibited the growth of FA HNSCC cell line OHSU-974 in athymic mice. Furthermore, PB was found to be significantly effective in inhibiting invasive parameters, such MMPs secretion and invasion through Matrigel. These findings suggest potential of PB in treatment of FA related HNSCC.