Anti-tumor Activity of the Novel Hexahydrocannabinol Analog LYR-8 in Human Colorectal Tumor Xenograft Is Mediated through the Inhibition of Akt and Hypoxia-Inducible Factor-1α Activation
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- Thapa Dinesh
- College of Pharmacy, Yeungnam University
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- Kang Youra
- College of Pharmacy, Yeungnam University
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- Park Pil-Hoon
- College of Pharmacy, Yeungnam University
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- Noh Seok Kyun
- School of Chemical Engineering and Technology, Yeungnam University
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- Lee Yong Rok
- School of Chemical Engineering and Technology, Yeungnam University
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- Han Sung Soo
- Department of Nano, Medical & Polymer Materials, College of Engineering, Yeungnam University
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- Ku Sae Kwang
- College of Oriental Medicine, Daegu Hanny University
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- Jung Yunjin
- College of Pharmacy, Pusan National University
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- Kim Jung-Ae
- College of Pharmacy, Yeungnam University
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Cannabinoid compounds have been shown to exert anti-tumor effects by affecting angiogenesis, invasion, and metastasis. In the present study, we examined the action mechanism by which LYR-8, a novel hexahydrocannabinol analog, exerts anti-angiogenic and anti-tumor activity in human cancer xenografts. In the xenografted tumor tissues, LYR-8 significantly reduced the expression of hypoxia-inducible factor-1 alpha (HIF-1α), a transcription factor responsible for induction of angiogenesis-promoting factors, and its target genes, vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). In HT-29 human colon cancer cells treated with a hypoxia-inducing agent (CoCl2), LYR-8 dose-dependently suppressed the induction of HIF-1α and subsequently its targets, VEGF and COX-2. In addition, highly elevated prostaglandin E2 (PGE2) concentrations in CoCl2-treated HT-29 cells were also significantly suppressed by LYR-8. However, LYR-8 alone in the absence of CoCl2 did not alter the basal expression of VEGF and COX-2, or PGE2 production. Furthermore, LYR-8 effectively suppressed Akt signaling, which corresponded to the suppression of CoCl2-induced HIF-1α accumulation. Taken together, LYR-8 exerts anti-tumor effects through the inhibition of Akt and HIF-1α activation, and subsequently suppressing factors regulating tumor microenvironment, such as VEGF and COX-2. These results indicate a novel function of cannabinoid-like compound LYR-8 as an anti-tumor agent with a HIF-1α inhibitory activity.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 35 (6), 924-932, 2012
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204632812032
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- NII論文ID
- 130001872175
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC38jgslChuw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 023665645
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- PubMed
- 22687485
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可