6-(1-Oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone inhibits Lewis lung cancer by antiangiogenesis and apoptosis

Jeong Lee Hyo, Hyo Jung Lee, Gyu Yong Song, Guangxun Li, Jae Ho Lee, Junxuan Lu, Sung Hoon Kim

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Lung cancer is a leading cause of cancer mortality worldwide. Novel and nontoxic agents targeting angiogenesis and tumor cell proliferation and survival are desirable for lung cancer chemoprevention and treatment. Previously we have reported that 6-(1-oxo-butyl)-5,8-dimethoxy-1,4-naphthoquinone (OXO) exhibits anti-tumor activity against S-180 sarcoma in vitro and in vivo. Here we studied the anti-angiogenic and apoptogenic attributes of OXO in vitro and in vivo targeting lung cancer. In human umbilical vein endothelial cells (HUVECs), we show that OXO more potently inhibited VEGF-stimulated than basic bFGF-stimulated HUVEC proliferation and capillary differentiation. In Lewis lung carcinoma (LLC) cells, OXO not only induces S-phase arrest and mitochondria/caspase-9 pathway mediated apoptosis, but also effectively down-regulated the hypoxia-induced expression of HIF-1α and VEGF at mRNA and protein levels in LLC and decreased VEGF secretion into conditioned culture media. OXO significantly reduced in vivo functional angiogenesis in the mouse Matrigel plug assay. Furthermore, OXO potently inhibited the growth of LLC cells inoculated on the flank of syngenic mice at dosages that did not affect their body weight. The in vivo anti-cancer effect was associated with decreased HIF-1α and VEGF expression, decreased microvessel density as well as a reduction of tumor cell proliferation and increased tumor cell apoptosis. Taken together, these results demonstrate that OXO exerts anti-cancer activity through anti-angiogenesis and tumor cell cycle arrest and apoptosis. These findings warrant additional studies of OXO as a novel agent for the chemoprevention and treatment of lung cancer.

Original languageEnglish (US)
Pages (from-to)2481-2490
Number of pages10
JournalInternational Journal of Cancer
Volume120
Issue number11
DOIs
StatePublished - Jun 1 2007

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Lung Neoplasms
Apoptosis
Lewis Lung Carcinoma
Vascular Endothelial Growth Factor A
Neoplasms
Human Umbilical Vein Endothelial Cells
Chemoprevention
Cell Proliferation
Sarcoma 180
6-(1-oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone
Caspase 9
Conditioned Culture Medium
Microvessels
Cell Cycle Checkpoints
S Phase
Cell Survival
Mitochondria
Body Weight
Messenger RNA
Mortality

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hyo, Jeong Lee ; Lee, Hyo Jung ; Song, Gyu Yong ; Li, Guangxun ; Lee, Jae Ho ; Lu, Junxuan ; Kim, Sung Hoon. / 6-(1-Oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone inhibits Lewis lung cancer by antiangiogenesis and apoptosis. In: International Journal of Cancer. 2007 ; Vol. 120, No. 11. pp. 2481-2490.
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abstract = "Lung cancer is a leading cause of cancer mortality worldwide. Novel and nontoxic agents targeting angiogenesis and tumor cell proliferation and survival are desirable for lung cancer chemoprevention and treatment. Previously we have reported that 6-(1-oxo-butyl)-5,8-dimethoxy-1,4-naphthoquinone (OXO) exhibits anti-tumor activity against S-180 sarcoma in vitro and in vivo. Here we studied the anti-angiogenic and apoptogenic attributes of OXO in vitro and in vivo targeting lung cancer. In human umbilical vein endothelial cells (HUVECs), we show that OXO more potently inhibited VEGF-stimulated than basic bFGF-stimulated HUVEC proliferation and capillary differentiation. In Lewis lung carcinoma (LLC) cells, OXO not only induces S-phase arrest and mitochondria/caspase-9 pathway mediated apoptosis, but also effectively down-regulated the hypoxia-induced expression of HIF-1α and VEGF at mRNA and protein levels in LLC and decreased VEGF secretion into conditioned culture media. OXO significantly reduced in vivo functional angiogenesis in the mouse Matrigel plug assay. Furthermore, OXO potently inhibited the growth of LLC cells inoculated on the flank of syngenic mice at dosages that did not affect their body weight. The in vivo anti-cancer effect was associated with decreased HIF-1α and VEGF expression, decreased microvessel density as well as a reduction of tumor cell proliferation and increased tumor cell apoptosis. Taken together, these results demonstrate that OXO exerts anti-cancer activity through anti-angiogenesis and tumor cell cycle arrest and apoptosis. These findings warrant additional studies of OXO as a novel agent for the chemoprevention and treatment of lung cancer.",
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6-(1-Oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone inhibits Lewis lung cancer by antiangiogenesis and apoptosis. / Hyo, Jeong Lee; Lee, Hyo Jung; Song, Gyu Yong; Li, Guangxun; Lee, Jae Ho; Lu, Junxuan; Kim, Sung Hoon.

In: International Journal of Cancer, Vol. 120, No. 11, 01.06.2007, p. 2481-2490.

Research output: Contribution to journalArticle

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AU - Hyo, Jeong Lee

AU - Lee, Hyo Jung

AU - Song, Gyu Yong

AU - Li, Guangxun

AU - Lee, Jae Ho

AU - Lu, Junxuan

AU - Kim, Sung Hoon

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AB - Lung cancer is a leading cause of cancer mortality worldwide. Novel and nontoxic agents targeting angiogenesis and tumor cell proliferation and survival are desirable for lung cancer chemoprevention and treatment. Previously we have reported that 6-(1-oxo-butyl)-5,8-dimethoxy-1,4-naphthoquinone (OXO) exhibits anti-tumor activity against S-180 sarcoma in vitro and in vivo. Here we studied the anti-angiogenic and apoptogenic attributes of OXO in vitro and in vivo targeting lung cancer. In human umbilical vein endothelial cells (HUVECs), we show that OXO more potently inhibited VEGF-stimulated than basic bFGF-stimulated HUVEC proliferation and capillary differentiation. In Lewis lung carcinoma (LLC) cells, OXO not only induces S-phase arrest and mitochondria/caspase-9 pathway mediated apoptosis, but also effectively down-regulated the hypoxia-induced expression of HIF-1α and VEGF at mRNA and protein levels in LLC and decreased VEGF secretion into conditioned culture media. OXO significantly reduced in vivo functional angiogenesis in the mouse Matrigel plug assay. Furthermore, OXO potently inhibited the growth of LLC cells inoculated on the flank of syngenic mice at dosages that did not affect their body weight. The in vivo anti-cancer effect was associated with decreased HIF-1α and VEGF expression, decreased microvessel density as well as a reduction of tumor cell proliferation and increased tumor cell apoptosis. Taken together, these results demonstrate that OXO exerts anti-cancer activity through anti-angiogenesis and tumor cell cycle arrest and apoptosis. These findings warrant additional studies of OXO as a novel agent for the chemoprevention and treatment of lung cancer.

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