DOI: 10.1111/j.1349-7006.2001.tb02159.x. A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxia‐inducible Factor‐1α and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts

A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxia‐inducible Factor‐1α and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts

10.1111/j.1349-7006.2001.tb02159.x

Crossref journal-article

Wiley

Japanese Journal of Cancer Research (311)

Abstract

A novel oxime derivative of radicicol, KF58333, binds to the heat shock protein 90 (Hsp90) and destabilizes its associated signaling molecules. These effects play a critical role in the growth inhibition of tumor cells. To further investigate the effects of this agent, it was administered to two human breast cancer cell lines, KPL‐1 and KPL‐4, both in vitro and in vivo. KF58333 dose‐dependently inhibited the growth and vascular endothelial growth factor (VEGF) secretion, concomitantly with a decrease in VEGF mRNA expression, in each cell line. This agent also suppressed the increase of VEGF secretion and expression induced by hypoxia (1% O2). Intravenous injections of this agent into nude mice bearing either KPL‐1 or KPL‐4 xenografts significantly inhibited the tumor growth associated with a decrease in the Ki67 labeling index and microvascular area and an increase in apoptosis and the necrotic area. These findings indicate that the antitumor activity of this radicicol derivative may be partly mediated by decreasing VEGF secretion from tumor cells and inhibiting tumor angiogenesis. To explore the action mechanisms of the anti‐angiogenic effect, the expression level of hypoxia‐inducible factor (HIF)‐lα was investigated. KF58333 provided a significant decrease in the HTF‐lα protein expression under both normoxic and hypoxic conditions. In contrast, the mRNA expression of HIF‐lα was not decreased by this agent. It is suggested that the post‐transcriptional down‐regulation of HIF‐lα expression by this agent may result in a decrease of VEGF expression and tumor angiogenesis.

Bibliography

Kurebayashi, J., Otsuki, T., Kurosumi, M., Soga, S., Akinaga, S., & Sonoo, H. (2001). A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxiaâinducible Factorâ1Î± and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts. Japanese Journal of Cancer Research, 92(12), 1342â1351. Portico.

Authors 6

Junichi Kurebayashi (first)
Takemi Otsuki (additional)
Masafumi Kurosumi (additional)
Shiro Soga (additional)
Shiro Akinaga (additional)
Hiroshi Sonoo (additional)

References 37 Referenced 45

10.1016/S0006-2952(98)00120-8
10.1002/ijc.2910510418
10.1073/pnas.91.18.8324
10.1210/mend.13.9.0339
10.1093/jnci/92.3.242
10.1016/S0959-440X(99)00047-0
10.1093/jnci/91.22.1940
{'key': 'e_1_2_1_9_2', 'first-page': '2931', 'article-title': 'KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules', 'volume': '59', 'author': 'Soga S.', 'year': '1999', 'journal-title': 'Cancer Res.'} / Cancer Res. / KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules by Soga S. (1999)
10.1182/blood.V96.6.2284 / Blood / Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential Gl phase accumulation against chronic myelogenous leukemia cells through destabilization of Bcr‐Abl with Hsp90 complex by Shiotsu Y. (2000)
10.1007/s002800100373
{'key': 'e_1_2_1_12_2', 'first-page': '3940', 'article-title': 'Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product‐dependent Gl arrest', 'volume': '60', 'author': 'Srethapakdi M.', 'year': '2000', 'journal-title': 'Cancer Res.'} / Cancer Res. / Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product‐dependent Gl arrest by Srethapakdi M. (2000)
{'key': 'e_1_2_1_13_2', 'first-page': '2945', 'article-title': 'Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells', 'volume': '61', 'author': 'Munster P. N.', 'year': '2001', 'journal-title': 'Cancer Res.'} / Cancer Res. / Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells by Munster P. N. (2001)
{'key': 'e_1_2_1_14_2', 'first-page': '4003', 'article-title': 'Inhibition of signal transduction by the Hsp90 inhibitor 17‐allylamino‐17‐demethoxygeldanamycin results in cytostasis and apoptosis', 'volume': '61', 'author': 'Hostein L', 'year': '2001', 'journal-title': 'Cancer Res.'} / Cancer Res. / Inhibition of signal transduction by the Hsp90 inhibitor 17‐allylamino‐17‐demethoxygeldanamycin results in cytostasis and apoptosis by Hostein L (2001)
10.1038/nm0195-27
10.1093/carcin/21.3.505
10.1016/0014-2999(93)90206-W
10.1038/bjc.1995.163
10.1038/sj.bjc.6690114
10.1006/bbrc.1999.1889
{'key': 'e_1_2_1_21_2', 'first-page': '5830', 'article-title': 'Overexpression of hypoxia‐inducible factor 1 alpha in common human cancers and their metastases', 'volume': '59', 'author': 'Zhong H.', 'year': '1999', 'journal-title': 'Cancer Res.'} / Cancer Res. / Overexpression of hypoxia‐inducible factor 1 alpha in common human cancers and their metastases by Zhong H. (1999)
10.1016/S0014-5793(99)01359-9
10.1111/j.1349-7006.1999.tb00844.x
10.1159/000055256
10.1007/BF00121138
10.1159/000012154
{'key': 'e_1_2_1_27_2', 'first-page': '3221', 'article-title': 'Expression of bcl‐2 and apoptotic DNA fragmentation in human endometrial adenocarcinoma cells', 'volume': '16', 'author': 'Kuwashima Y.', 'year': '1996', 'journal-title': 'Anticancer Res.'} / Anticancer Res. / Expression of bcl‐2 and apoptotic DNA fragmentation in human endometrial adenocarcinoma cells by Kuwashima Y. (1996)
10.1007/BF00121205
{'key': 'e_1_2_1_29_2', 'first-page': '1434', 'article-title': 'Estrogen receptors in human myeloma cells', 'volume': '60', 'author': 'Otsuki T.', 'year': '2000', 'journal-title': 'Cancer Res.'} / Cancer Res. / Estrogen receptors in human myeloma cells by Otsuki T. (2000)
{'key': 'e_1_2_1_30_2', 'first-page': '71', 'article-title': 'Overview of the trastuzumab (Herceptin) anti‐HER2 monoclonal antibody clinical program in HER2‐overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group', 'volume': '26', 'author': 'Shak S.', 'year': '1999', 'journal-title': 'Semin. Oncol.'} / Semin. Oncol. / Overview of the trastuzumab (Herceptin) anti‐HER2 monoclonal antibody clinical program in HER2‐overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group by Shak S. (1999)
{'key': 'e_1_2_1_31_2', 'first-page': '3522', 'article-title': 'Differential signaling by an anti‐pi 85(HER2) antibody and heregulin', 'volume': '60', 'author': 'Le X. F.', 'year': '2000', 'journal-title': 'Cancer Res.'} / Cancer Res. / Differential signaling by an anti‐pi 85(HER2) antibody and heregulin by Le X. F. (2000)
10.1126/science.287.5460.1969
10.1074/jbc.275.14.10661
10.1074/jbc.274.46.32631
10.1080/10409230091169186
10.1016/S0167-4781(99)00048-2
10.1006/bbrc.1999.0878
{'key': 'e_1_2_1_38_2', 'first-page': '253', 'article-title': 'Role of HIF‐1 as a transcription factor involved in embryonic development, cancer progression and apoptosis (review)', 'volume': '5', 'author': 'Minet E.', 'year': '2000', 'journal-title': 'Int. J. Mol. Med.'} / Int. J. Mol. Med. / Role of HIF‐1 as a transcription factor involved in embryonic development, cancer progression and apoptosis (review) by Minet E. (2000)

Dates

Type	When
Created	20 years ago (Aug. 22, 2005, 7:50 a.m.)
Deposited	1 year, 9 months ago (Nov. 19, 2023, 9 a.m.)
Indexed	1 year, 1 month ago (July 13, 2024, 3:09 a.m.)
Issued	23 years, 8 months ago (Dec. 1, 2001)
Published	23 years, 8 months ago (Dec. 1, 2001)
Published Online	20 years ago (Aug. 22, 2005)
Published Print	23 years, 8 months ago (Dec. 1, 2001)

Funders 0

None

BibTeX

@article{Kurebayashi_2001, title={A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxia‐inducible Factor‐1α and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts}, volume={92}, ISSN={0910-5050}, url={http://dx.doi.org/10.1111/j.1349-7006.2001.tb02159.x}, DOI={10.1111/j.1349-7006.2001.tb02159.x}, number={12}, journal={Japanese Journal of Cancer Research}, publisher={Wiley}, author={Kurebayashi, Junichi and Otsuki, Takemi and Kurosumi, Masafumi and Soga, Shiro and Akinaga, Shiro and Sonoo, Hiroshi}, year={2001}, month=dec, pages={1342–1351} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        7,
        13
      ]
    ],
    "date-time": "2024-07-13T07:09:53Z",
    "timestamp": 1720854593565
  },
  "reference-count": 37,
  "publisher": "Wiley",
  "issue": "12",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2005,
            8,
            22
          ]
        ],
        "date-time": "2005-08-22T00:00:00Z",
        "timestamp": 1124668800000
      },
      "content-version": "vor",
      "delay-in-days": 1360,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        12
      ]
    ]
  },
  "abstract": "<jats:p>A novel oxime derivative of radicicol, KF58333, binds to the heat shock protein 90 (Hsp90) and destabilizes its associated signaling molecules. These effects play a critical role in the growth inhibition of tumor cells. To further investigate the effects of this agent, it was administered to two human breast cancer cell lines, KPL\u20101 and KPL\u20104, both <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo.</jats:italic> KF58333 dose\u2010dependently inhibited the growth and vascular endothelial growth factor (VEGF) secretion, concomitantly with a decrease in VEGF mRNA expression, in each cell line. This agent also suppressed the increase of VEGF secretion and expression induced by hypoxia (1% O<jats:sub>2</jats:sub>). Intravenous injections of this agent into nude mice bearing either KPL\u20101 or KPL\u20104 xenografts significantly inhibited the tumor growth associated with a decrease in the Ki67 labeling index and microvascular area and an increase in apoptosis and the necrotic area. These findings indicate that the antitumor activity of this radicicol derivative may be partly mediated by decreasing VEGF secretion from tumor cells and inhibiting tumor angiogenesis. To explore the action mechanisms of the anti\u2010angiogenic effect, the expression level of hypoxia\u2010inducible factor (HIF)\u2010l\u03b1 was investigated. KF58333 provided a significant decrease in the HTF\u2010l\u03b1 protein expression under both normoxic and hypoxic conditions. In contrast, the mRNA expression of HIF\u2010l\u03b1 was not decreased by this agent. It is suggested that the post\u2010transcriptional down\u2010regulation of HIF\u2010l\u03b1 expression by this agent may result in a decrease of VEGF expression and tumor angiogenesis.</jats:p>",
  "DOI": "10.1111/j.1349-7006.2001.tb02159.x",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        8,
        22
      ]
    ],
    "date-time": "2005-08-22T11:50:16Z",
    "timestamp": 1124711416000
  },
  "page": "1342-1351",
  "source": "Crossref",
  "is-referenced-by-count": 45,
  "title": "A Radicicol Derivative, KF58333, Inhibits Expression of Hypoxia\u2010inducible Factor\u20101\u03b1 and Vascular Endothelial Growth Factor, Angiogenesis and Growth of Human Breast Cancer Xenografts",
  "prefix": "10.1111",
  "volume": "92",
  "author": [
    {
      "given": "Junichi",
      "family": "Kurebayashi",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Takemi",
      "family": "Otsuki",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Masafumi",
      "family": "Kurosumi",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Shiro",
      "family": "Soga",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Shiro",
      "family": "Akinaga",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Hiroshi",
      "family": "Sonoo",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2005,
        8,
        22
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_1_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-2952(98)00120-8"
    },
    {
      "key": "e_1_2_1_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/ijc.2910510418"
    },
    {
      "key": "e_1_2_1_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.18.8324"
    },
    {
      "key": "e_1_2_1_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1210/mend.13.9.0339"
    },
    {
      "key": "e_1_2_1_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jnci/92.3.242"
    },
    {
      "key": "e_1_2_1_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0959-440X(99)00047-0"
    },
    {
      "key": "e_1_2_1_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jnci/91.22.1940"
    },
    {
      "key": "e_1_2_1_9_2",
      "first-page": "2931",
      "article-title": "KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules",
      "volume": "59",
      "author": "Soga S.",
      "year": "1999",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_10_2",
      "doi-asserted-by": "crossref",
      "first-page": "2284",
      "DOI": "10.1182/blood.V96.6.2284",
      "article-title": "Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential Gl phase accumulation against chronic myelogenous leukemia cells through destabilization of Bcr\u2010Abl with Hsp90 complex",
      "volume": "96",
      "author": "Shiotsu Y.",
      "year": "2000",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_1_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s002800100373"
    },
    {
      "key": "e_1_2_1_12_2",
      "first-page": "3940",
      "article-title": "Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product\u2010dependent Gl arrest",
      "volume": "60",
      "author": "Srethapakdi M.",
      "year": "2000",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_13_2",
      "first-page": "2945",
      "article-title": "Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells",
      "volume": "61",
      "author": "Munster P. N.",
      "year": "2001",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_14_2",
      "first-page": "4003",
      "article-title": "Inhibition of signal transduction by the Hsp90 inhibitor 17\u2010allylamino\u201017\u2010demethoxygeldanamycin results in cytostasis and apoptosis",
      "volume": "61",
      "author": "Hostein L",
      "year": "2001",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm0195-27"
    },
    {
      "key": "e_1_2_1_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/carcin/21.3.505"
    },
    {
      "key": "e_1_2_1_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-2999(93)90206-W"
    },
    {
      "key": "e_1_2_1_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/bjc.1995.163"
    },
    {
      "key": "e_1_2_1_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.bjc.6690114"
    },
    {
      "key": "e_1_2_1_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1999.1889"
    },
    {
      "key": "e_1_2_1_21_2",
      "first-page": "5830",
      "article-title": "Overexpression of hypoxia\u2010inducible factor 1 alpha in common human cancers and their metastases",
      "volume": "59",
      "author": "Zhong H.",
      "year": "1999",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(99)01359-9"
    },
    {
      "key": "e_1_2_1_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1349-7006.1999.tb00844.x"
    },
    {
      "key": "e_1_2_1_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1159/000055256"
    },
    {
      "key": "e_1_2_1_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00121138"
    },
    {
      "key": "e_1_2_1_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1159/000012154"
    },
    {
      "key": "e_1_2_1_27_2",
      "first-page": "3221",
      "article-title": "Expression of bcl\u20102 and apoptotic DNA fragmentation in human endometrial adenocarcinoma cells",
      "volume": "16",
      "author": "Kuwashima Y.",
      "year": "1996",
      "journal-title": "Anticancer Res."
    },
    {
      "key": "e_1_2_1_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00121205"
    },
    {
      "key": "e_1_2_1_29_2",
      "first-page": "1434",
      "article-title": "Estrogen receptors in human myeloma cells",
      "volume": "60",
      "author": "Otsuki T.",
      "year": "2000",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_30_2",
      "first-page": "71",
      "article-title": "Overview of the trastuzumab (Herceptin) anti\u2010HER2 monoclonal antibody clinical program in HER2\u2010overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group",
      "volume": "26",
      "author": "Shak S.",
      "year": "1999",
      "journal-title": "Semin. Oncol."
    },
    {
      "key": "e_1_2_1_31_2",
      "first-page": "3522",
      "article-title": "Differential signaling by an anti\u2010pi 85(HER2) antibody and heregulin",
      "volume": "60",
      "author": "Le X. F.",
      "year": "2000",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_2_1_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.287.5460.1969"
    },
    {
      "key": "e_1_2_1_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.275.14.10661"
    },
    {
      "key": "e_1_2_1_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.46.32631"
    },
    {
      "key": "e_1_2_1_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1080/10409230091169186"
    },
    {
      "key": "e_1_2_1_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0167-4781(99)00048-2"
    },
    {
      "key": "e_1_2_1_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1999.0878"
    },
    {
      "key": "e_1_2_1_38_2",
      "first-page": "253",
      "article-title": "Role of HIF\u20101 as a transcription factor involved in embryonic development, cancer progression and apoptosis (review)",
      "volume": "5",
      "author": "Minet E.",
      "year": "2000",
      "journal-title": "Int. J. Mol. Med."
    }
  ],
  "container-title": "Japanese Journal of Cancer Research",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1349-7006.2001.tb02159.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.2001.tb02159.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        11,
        19
      ]
    ],
    "date-time": "2023-11-19T14:00:47Z",
    "timestamp": 1700402447000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2001.tb02159.x"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        12
      ]
    ]
  },
  "references-count": 37,
  "journal-issue": {
    "issue": "12",
    "published-print": {
      "date-parts": [
        [
          2001,
          12
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1111/j.1349-7006.2001.tb02159.x"
  ],
  "URL": "http://dx.doi.org/10.1111/j.1349-7006.2001.tb02159.x",
  "relation": {},
  "ISSN": [
    "0910-5050"
  ],
  "subject": [],
  "container-title-short": "Japanese Journal of Cancer Research",
  "published": {
    "date-parts": [
      [
        2001,
        12
      ]
    ]
  }
}