Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts
<p>Abstract</p> <p>Background</p> <p>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 g...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-07-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/394 |
| _version_ | 1811283341798801408 |
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| author | Syed Zanobia Gill Jennifer N Prince Misty Robbins Delira Remeika Angela Shi Runhua Kleiner-Hancock Heather E Adegboyega Patrick Mathis J Michael Clifford John L |
| author_facet | Syed Zanobia Gill Jennifer N Prince Misty Robbins Delira Remeika Angela Shi Runhua Kleiner-Hancock Heather E Adegboyega Patrick Mathis J Michael Clifford John L |
| author_sort | Syed Zanobia |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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-<it>O</it>-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-<it>trans </it>retinoic acid (ATRA) for suppressing SCC tumor growth.</p> <p>Methods</p> <p>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 × 10<sup>6 </sup>SRB12-p9 cells s.c., palpated and weighed twice a week for 28 days following injection.</p> <p>Results</p> <p>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%.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-04-13T02:09:45Z |
| format | Article |
| id | doaj.art-de431faac7db48438134c575c0314431 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T02:09:45Z |
| publishDate | 2010-07-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-de431faac7db48438134c575c03144312022-12-22T03:07:20ZengBMCBMC Cancer1471-24072010-07-0110139410.1186/1471-2407-10-394Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenograftsSyed ZanobiaGill Jennifer NPrince MistyRobbins DeliraRemeika AngelaShi RunhuaKleiner-Hancock Heather EAdegboyega PatrickMathis J MichaelClifford John L<p>Abstract</p> <p>Background</p> <p>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-<it>O</it>-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-<it>trans </it>retinoic acid (ATRA) for suppressing SCC tumor growth.</p> <p>Methods</p> <p>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 × 10<sup>6 </sup>SRB12-p9 cells s.c., palpated and weighed twice a week for 28 days following injection.</p> <p>Results</p> <p>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%.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2407/10/394 |
| spellingShingle | Syed Zanobia Gill Jennifer N Prince Misty Robbins Delira Remeika Angela Shi Runhua Kleiner-Hancock Heather E Adegboyega Patrick Mathis J Michael Clifford John L Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts BMC Cancer |
| title | Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts |
| title_full | Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts |
| title_fullStr | Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts |
| title_full_unstemmed | Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts |
| title_short | Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts |
| title_sort | effects of atra combined with citrus and ginger derived compounds in human scc xenografts |
| url | http://www.biomedcentral.com/1471-2407/10/394 |
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