TY - JOUR
T1 - Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts
AU - Kleiner-Hancock, Heather E.
AU - Shi, Runhua
AU - Remeika, Angela
AU - Robbins, Delira
AU - Prince, Misty
AU - Gill, Jennifer N.
AU - Syed, Zanobia
AU - Adegboyega, Patrick
AU - Mathis, J. Michael
AU - Clifford, John L.
N1 - Funding Information:
The authors gratefully acknowledge the expert technical assistance of Tracee Terry, in the Small Animal Imaging Center. This research was supported in part by grants from the Feist-Weiller Cancer Center and the Department of Pharmacology, Toxicology & Neuroscience. This research was also supported, in part, by a National Cancer Institute grant 1K22CA102005-01A2 (HEK) and 1R21CA116324 (JLC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Ms. Remeika was supported by the Summer Undergraduate Pharmacology Experience in Research (SUPER) program, which received funding from the American Society for Pharmacology and Experimental Therapeutics (ASPET) Summer Undergraduate Research Fellowship (SURF), the LSU Health Sciences Foundation, and the Department of Pharmacology, Toxicology, and Neuroscience.
PY - 2010/7/26
Y1 - 2010/7/26
N2 - Background: NF-κB is a survival signaling transcription factor complex involved in the malignant phenotype of many cancers, including squamous cell carcinomas (SCC). The citrus coumarin, auraptene (AUR), and the ethno-medicinal ginger (Alpinia galanga) phenylpropanoid, 1'-acetoxychavicol acetate (ACA), were previously shown to suppress 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse skin tumor promotion. The goal of the present study was to determine whether AUR and ACA are effective either alone or in combination with all-trans retinoic acid (ATRA) for suppressing SCC tumor growth.Methods: We first determined the effects of orally administered ACA (100 mg/kg bw) and AUR (200 mg/kg bw) on lipopolysaccharide (LPS)-induced NF-κB activation in NF-κB-RE-luc (Oslo) luciferase reporter mice. Dietary administration of AUR and ACA ± ATRA was next evaluated in a xenograft mouse model. Female SCID/bg mice were fed diets containing the experimental compounds, injected with 1 × 106 SRB12-p9 cells s.c., palpated and weighed twice a week for 28 days following injection.Results: Both ACA and AUR suppressed LPS-induced NF-κB activation in the report mice. In the xenograft model, AUR (1000 ppm) and ACA (500 ppm) modestly suppressed tumor volume. However, in combination with ATRA at 5, 10, and 30 ppm, ACA 500 ppm significantly inhibited tumor volume by 56%, 62%, and 98%, respectively. The effect of ATRA alone was 37%, 33%, and 93% inhibition, respectively. AUR 1000 ppm and ATRA 10 ppm were not very effective when administered alone, but when combined, strongly suppressed tumor volume by 84%.Conclusions: Citrus AUR may synergize the tumor suppressive effects of ATRA, while ACA may prolong the inhibitory effects of ATRA. Further studies will be necessary to determine whether these combinations may be useful in the control of human SCC.
AB - Background: NF-κB is a survival signaling transcription factor complex involved in the malignant phenotype of many cancers, including squamous cell carcinomas (SCC). The citrus coumarin, auraptene (AUR), and the ethno-medicinal ginger (Alpinia galanga) phenylpropanoid, 1'-acetoxychavicol acetate (ACA), were previously shown to suppress 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse skin tumor promotion. The goal of the present study was to determine whether AUR and ACA are effective either alone or in combination with all-trans retinoic acid (ATRA) for suppressing SCC tumor growth.Methods: We first determined the effects of orally administered ACA (100 mg/kg bw) and AUR (200 mg/kg bw) on lipopolysaccharide (LPS)-induced NF-κB activation in NF-κB-RE-luc (Oslo) luciferase reporter mice. Dietary administration of AUR and ACA ± ATRA was next evaluated in a xenograft mouse model. Female SCID/bg mice were fed diets containing the experimental compounds, injected with 1 × 106 SRB12-p9 cells s.c., palpated and weighed twice a week for 28 days following injection.Results: Both ACA and AUR suppressed LPS-induced NF-κB activation in the report mice. In the xenograft model, AUR (1000 ppm) and ACA (500 ppm) modestly suppressed tumor volume. However, in combination with ATRA at 5, 10, and 30 ppm, ACA 500 ppm significantly inhibited tumor volume by 56%, 62%, and 98%, respectively. The effect of ATRA alone was 37%, 33%, and 93% inhibition, respectively. AUR 1000 ppm and ATRA 10 ppm were not very effective when administered alone, but when combined, strongly suppressed tumor volume by 84%.Conclusions: Citrus AUR may synergize the tumor suppressive effects of ATRA, while ACA may prolong the inhibitory effects of ATRA. Further studies will be necessary to determine whether these combinations may be useful in the control of human SCC.
UR - http://www.scopus.com/inward/record.url?scp=77954876959&partnerID=8YFLogxK
U2 - 10.1186/1471-2407-10-394
DO - 10.1186/1471-2407-10-394
M3 - Article
C2 - 20659317
AN - SCOPUS:77954876959
SN - 1471-2407
VL - 10
JO - BMC Cancer
JF - BMC Cancer
M1 - 394
ER -