Piperazine-based Alpha-1 AR Blocker, Naftopidil, Selectively Suppresses Malignant Human Bladder Cells via Induction of Apoptosis
A retrospective observational cohort study has shown that exposure to alpha-1 adrenergic receptor (AR) blocker reduces the risk of bladder cancer (BCa). We investigated the antitumor activity of alpha-1 blockers, that are administered long-term therapeutically, in BCa. The antitumor activity of alph...
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| Veröffentlicht in: | Anticancer research 2016-04, Vol.36 (4), p.1563-1570 |
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| container_title | Anticancer research |
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| creator | Nakagawa, Yusuke U Nagaya, Hisao Miyata, Takeaki Wada, Yoshitaka Oyama, Tsunehiro Gotoh, Akinobu |
| description | A retrospective observational cohort study has shown that exposure to alpha-1 adrenergic receptor (AR) blocker reduces the risk of bladder cancer (BCa). We investigated the antitumor activity of alpha-1 blockers, that are administered long-term therapeutically, in BCa. The antitumor activity of alpha-1 blockers was evaluated in terms of cell viability, cell cycle, competition, and apoptotic signaling in BCa cells. Our cell viability studies showed that naftopidil was one of the strongest alpha-1 AR blockers, regarding its antitumor action in BCa cells, independent of the grade of malignancy, but with no similar action on normal human bladder cells. Oral administration of naftopidil reduced tumor volume in a xenograft model. Our own competitive analysis using an alpha-1 AR agonist and other alpha-1 AR blockers showed that naftopidil activated cell death signaling without inhibitory action on alpha-1 ARs. We conclude that naftopidil has potential as an antitumor drug against BCa in vitro and in vivo. This finding provides a rationale for developing naftopidil in grade-independent treatment of BCa. |
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We investigated the antitumor activity of alpha-1 blockers, that are administered long-term therapeutically, in BCa. The antitumor activity of alpha-1 blockers was evaluated in terms of cell viability, cell cycle, competition, and apoptotic signaling in BCa cells. Our cell viability studies showed that naftopidil was one of the strongest alpha-1 AR blockers, regarding its antitumor action in BCa cells, independent of the grade of malignancy, but with no similar action on normal human bladder cells. Oral administration of naftopidil reduced tumor volume in a xenograft model. Our own competitive analysis using an alpha-1 AR agonist and other alpha-1 AR blockers showed that naftopidil activated cell death signaling without inhibitory action on alpha-1 ARs. We conclude that naftopidil has potential as an antitumor drug against BCa in vitro and in vivo. 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We investigated the antitumor activity of alpha-1 blockers, that are administered long-term therapeutically, in BCa. The antitumor activity of alpha-1 blockers was evaluated in terms of cell viability, cell cycle, competition, and apoptotic signaling in BCa cells. Our cell viability studies showed that naftopidil was one of the strongest alpha-1 AR blockers, regarding its antitumor action in BCa cells, independent of the grade of malignancy, but with no similar action on normal human bladder cells. Oral administration of naftopidil reduced tumor volume in a xenograft model. Our own competitive analysis using an alpha-1 AR agonist and other alpha-1 AR blockers showed that naftopidil activated cell death signaling without inhibitory action on alpha-1 ARs. We conclude that naftopidil has potential as an antitumor drug against BCa in vitro and in vivo. This finding provides a rationale for developing naftopidil in grade-independent treatment of BCa.</description><subject>Adrenergic alpha-Antagonists - pharmacology</subject><subject>Adrenergic alpha-Antagonists - therapeutic use</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Humans</subject><subject>Male</subject><subject>Mice, Nude</subject><subject>Naphthalenes - pharmacology</subject><subject>Naphthalenes - therapeutic use</subject><subject>Piperazines - pharmacology</subject><subject>Piperazines - therapeutic use</subject><subject>Tumor Burden - drug effects</subject><subject>Urinary Bladder Neoplasms - drug therapy</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kD1PwzAYhCMkREvhLyCPDI1kx4kdj6ECWql8iMIcvYnfgMGJTZxUKhM_nUjAdMtzp7s7iuZMKhbLjNNZdBrCO6VCqJyfRLNEUqEYT-bR96Px2MOX6TCuIKAmhfVvEDNSPJEr6-oP7JfkHprBeaONXZIdWqwHs0d7ILvR-x5DwEDuwJrXDrqBrMcWuskLWmNPVmhtIHsDZNPpcTK6jriGFN75wQUTzqLjBmzA8z9dRC8318-rdbx9uN2sim3sE8aGuJKVVphVXDUZZtOwuk4hF1LmOQWlBBVpzXiqEsQUK81UKoCjzGRDRQN1wxfR5W-u793niGEoWxPqqRx06MZQMpnTnDEm1IRe_KFj1aIufW9a6A_l_2v8B4T3aMY</recordid><startdate>201604</startdate><enddate>201604</enddate><creator>Nakagawa, Yusuke U</creator><creator>Nagaya, Hisao</creator><creator>Miyata, Takeaki</creator><creator>Wada, Yoshitaka</creator><creator>Oyama, Tsunehiro</creator><creator>Gotoh, Akinobu</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201604</creationdate><title>Piperazine-based Alpha-1 AR Blocker, Naftopidil, Selectively Suppresses Malignant Human Bladder Cells via Induction of Apoptosis</title><author>Nakagawa, Yusuke U ; 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This finding provides a rationale for developing naftopidil in grade-independent treatment of BCa.</abstract><cop>Greece</cop><pmid>27069132</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Anticancer research, 2016-04, Vol.36 (4), p.1563-1570 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Adrenergic alpha-Antagonists - pharmacology Adrenergic alpha-Antagonists - therapeutic use Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis - drug effects Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Humans Male Mice, Nude Naphthalenes - pharmacology Naphthalenes - therapeutic use Piperazines - pharmacology Piperazines - therapeutic use Tumor Burden - drug effects Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - pathology Xenograft Model Antitumor Assays |
| title | Piperazine-based Alpha-1 AR Blocker, Naftopidil, Selectively Suppresses Malignant Human Bladder Cells via Induction of Apoptosis |
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