1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol as a Potential Anticancer Drug

Kanno, Takeshi; Tanaka, Akito; Shimizu, Tadashi; Nakano, Takashi; Nishizaki, Tomoyuki

doi:10.1159/000351747

Cited by 16 publications

(18 citation statements)

References 21 publications

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“…Consistent with in vitro and in vivo animal findings in PCa, classical α-antagonists and their analogues appear to have broad activity, exhibiting cytotoxicity in other cancer cell lines including urogenital [44,65,66,67,68,69,70,71,72,73,74], gastrointestinal [73,74,75,76,77], lung [74,78], blood [79], brain [80,81] and thyroid [82]. Importantly, the cytotoxic and anti-proliferative effects are supported by several in vivo mice studies [48,66], suggesting ubiquitous anticancer actions of these drugs.…”

Section: Discussionsupporting

confidence: 64%

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

Batty

Pugh

Rathinam

et al. 2016

IJMS

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This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.

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Section: Discussionsupporting

confidence: 64%

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

Batty

Pugh

Rathinam

et al. 2016

IJMS

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“…To obtain the more potential anticancer drug, we have newly synthesized 21 naftopidil analogues and assessed the anticancer effect of these compounds. Among them the most expected hit was 1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol (HUHS1015) [ 3 ]. HUHS1015 induces apoptosis of a wide variety of cancer cell types; human malignant mesothelioma cell lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452 cells; human lung cancer cell lines A549, SBC-3, and Lu-65 cells; human hepatoma cell lines HepG2 and HuH-7 cells; human gastric cancer cell lines MKN28 and MKN45 cells; human bladder cancer cell lines 253 J, 5637, KK-47, TCCSUP, T24, and UM-UC-3 cells; human prostate cancer cell lines DU145, LNCaP, and PC-3 cells; and human renal cancer cell lines ACHN, RCC4-VHL, and 786-O cells [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Among them the most expected hit was 1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol (HUHS1015) [ 3 ]. HUHS1015 induces apoptosis of a wide variety of cancer cell types; human malignant mesothelioma cell lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452 cells; human lung cancer cell lines A549, SBC-3, and Lu-65 cells; human hepatoma cell lines HepG2 and HuH-7 cells; human gastric cancer cell lines MKN28 and MKN45 cells; human bladder cancer cell lines 253 J, 5637, KK-47, TCCSUP, T24, and UM-UC-3 cells; human prostate cancer cell lines DU145, LNCaP, and PC-3 cells; and human renal cancer cell lines ACHN, RCC4-VHL, and 786-O cells [ 3 ]. Moreover, HUHS1015 induces apoptosis of malignant pleural mesothelioma cells by activating caspase-4 and the effector caspase-3, in part as mediated through a mitochondrial pathway [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The newly synthesized anticancer drug HUHS1015 is useful for treatment of human gastric cancer

Kaku

Tsuchiya

Kanno

et al. 2015

Cancer Chemother Pharmacol

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Naftopidil is clinically for treatment of benign prostate hyperplasia, and emerging evidence has pointed to its anticancer effect. To obtain the anticancer drug with the potential greater than that of naftopidil, we have newly synthesized the naftopidil analogue HUHS1015. The present study investigated the mechanism underlying HUHS1015-induced apoptosis of human gastric cancer cells and assessed the possibility for clinical use as an innovative anticancer drug. HUHS1015 reduced cell viability for MKN28 human well-differentiated gastric adenocarcinoma cell line and MKN45 human poorly differentiated gastric adenocarcinoma cell line in a concentration (0.3–100 μM)-dependent manner more effectively than cisplatin, a chemo-drug widely used. In the flow cytometry using propidium iodide (PI) and annexin V, HUHS1015 significantly increased the population of PI-positive and annexin V-negative cells, corresponding to primary necrosis and that of PI-positive and annexin V-positive cells, corresponding to late apoptosis/secondary necrosis, both in the two cell types. HUHS1015 significantly activated caspase-3, caspase-4, and caspase-8 in MKN45 cells, while no obvious caspase activation was found in MKN28 cells. HUHS1015 upregulated expression of the tumor necrosis factor α (TNFα) mRNA and protein in MKN45 cells, allowing activation of caspase-8 through TNF receptor and the effector caspase-3. HUHS1015 clearly inhibited tumor growth in mice inoculated with MKN45 cells, with the survival rate higher than that for the anticancer drugs cisplatin, paclitaxel, and irinotecan. The results of the present study show that HUHS1015 induces caspase-independent and caspase-dependent apoptosis of MKN28 and MKN45 human gastric cancer cells, respectively, and effectively suppresses MKN45 cell proliferation.

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“…The newly synthesized naftopidil analogue HUHS1015 induces apoptosis in various cancer cell lines, including mesothelioma, lung cancer, hepatocellular carcinoma, gastric cancer, and bladder cancer [25]. HUHS1015 induced mitochondrial apoptosis and suppressed tumor growth in mice inoculated with mesothelioma cells [26].…”

Section: Humanized Anti-cd26 Monoclonal Antibody (Ys110) For the Treamentioning

confidence: 99%

Possible new therapeutic agents for malignant pleural mesothelioma: anti-CD26 monoclonal antibody and naftopidil

Nakano

Kuribayashi

Mikami

2016

Expert Review of Anticancer Therapy

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1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol as a Potential Anticancer Drug

Cited by 16 publications

References 21 publications

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

The newly synthesized anticancer drug HUHS1015 is useful for treatment of human gastric cancer

Possible new therapeutic agents for malignant pleural mesothelioma: anti-CD26 monoclonal antibody and naftopidil

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