1-\[2-(2-Methoxyphenylamino)ethylamino\]-3-(naphthalene-1-yloxy)propan-2-ol as a potential anticancer drug

Our plain-English summary of 1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol as a potential anticancer drug, by T. Kanno, A. Tanaka, T. Shimizu, et al (Pharmacology, 2013).

The study

• Authors: T. Kanno, A. Tanaka, T. Shimizu, T. Nakano, T. Nishizaki
• Journal: Pharmacology
• Published: 2013;91(5-6):339-45
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of the present study was to assess the anticancer effect of several naftopidil analogues on human malignant mesothelioma cell lines NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H, human lung cancer cell lines A549, SBC-3, and Lu-65, human hepatoma cell lines HepG2 and HuH-7, human gastric cancer cell lines MKN-28 and MKN-45, and human bladder cancer cell lines 253J, 5637, KK-47, TCCSUP, T24, and UM-UC-3, human prostate cancer cell lines DU145, LNCap, and PC-3, and human renal cancer cell lines ACHN, RCC4-VHL, and 786-O. We newly synthesized 21 naftopidil analogues, and of them 1-[2-(2-methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol (HUHS1015) most efficiently reduced cell viability for all the investigated malignant mesothelioma cell lines in a concentration (1-100 μmol/l)-dependent manner. HUHS1015 reduced cell viability for all other investigated cancer cell lines, to an extent similar to that for malignant mesothelioma cell lines. HUHS1015 activated caspase-3 and -4, without activating caspase-8 and -9, in malignant mesothelioma cell lines. The results of the present study, thus, indicate that HUHS1015 induces apoptosis in a variety of cancer cells, possibly by activating caspase-4 and the effector caspase-3.

Copyright © 2013 S. Karger AG, Basel.

In plain English

This short laboratory report tested newly made chemical relatives (analogues) of naftopidil, a prostate and blood-pressure drug, on human cancer cells grown in dishes. No people or animals were studied, and asbestos exposure was not studied. The authors made 21 analogues and applied them for 24 hours at 1 to 100 μmol/l to four malignant pleural mesothelioma cell lines. Seven analogues, including one called HUHS1015, lowered cell survival the most. HUHS1015 also lowered survival of non-cancerous mesothelial cells (Met5A), but less than in the mesothelioma cells. After 12 hours at 100 μmol/l, a marker of programmed cell death (apoptosis) appeared in 61, 69, 37 and 58% of cells in the four mesothelioma lines. HUHS1015 also lowered survival of lung, liver, stomach, bladder, prostate and kidney cancer cell lines. In mesothelioma cells it activated the enzymes caspase-3 and caspase-4 but not caspase-8 or caspase-9. The authors concluded that HUHS1015 works possibly through caspase-4 and caspase-3 and "could develop into a promising new anticancer drug." They noted that how it activates caspase-4 is unknown.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment, published as a short communication; the authors synthesized new naftopidil analogues and tested them on human cancer cell lines
• Who was studied: Human cell lines, not patients: four malignant pleural mesothelioma cell lines (NCI-H28, NCI-H2052, NCI-H2452, MSTO-211H), one nonmalignant mesothelial cell line (Met5A), and lung (A549, SBC-3, Lu-65), hepatic (HepG2, HuH-7), gastric (MKN-28, MKN-45), bladder (253J, 5637, KK-47, TCCSUP, T24, UM-UC-3), prostate (DU145, LNCap, PC-3) and renal (ACHN, RCC4-VHL, 786-O) cancer cell lines; Japan
• Exposure: No asbestos exposure was studied. Cells were treated with naftopidil or its 21 analogues, including HUHS1015, at 1 to 100 μmol/l for 24 hours (viability tests). HUHS1015 was given at 100 μmol/l for 12 hours (apoptosis staining) and for 3 to 9 hours (caspase tests).
• Main results:
  • In the four mesothelioma cell lines, seven of the 21 analogues (HUHS1002, HUHS1004, HUHS1014, HUHS1015, HUHS1017, HUHS1018, HUHS1019) had the highest potential to reduce cell viability
  • HUHS1015 reduced the viability of nonmalignant Met5A mesothelial cells in a dose-dependent way, but to a lesser extent than in the mesothelioma cell lines
  • After 12 hours of HUHS1015 at 100 μmol/l, TUNEL-positive (apoptotic) cells reached 61, 69, 37 and 58% of total cells in NCI-H28, NCI-H2052, NCI-H2452 and MSTO-211H cells respectively
  • HUHS1015 reduced cell viability in a concentration-dependent way in all the lung, hepatic, gastric, bladder, prostate and renal cancer cell lines tested
  • In the four mesothelioma cell lines, HUHS1015 activated caspase-3 and caspase-4
  • In the four mesothelioma cell lines, HUHS1015 did not activate caspase-8 or caspase-9
• The authors' conclusion: The authors concluded that HUHS1015 reduces cell viability in a variety of human cancer cell lines, including malignant mesothelioma cell lines, possibly by activating caspase-4 and the effector caspase-3, and that it could develop into a new anticancer drug
• Limitations the authors state:
  • The authors stated that it is unknown whether HUHS1015 induces endoplasmic reticulum stress, and how it activates caspase-4

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer, Stomach Cancer, Apoptosis.

Related studies

• Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma — Y. Kaku, H. Nagaya, et al. (2014)
• Mitochondria determine the efficacy of anticancer agents that interact with DNA but not the cytoskeleton — K. Hara, E. Kasahara, et al. (2011)
• Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma — I. Dell'Anno, S.A. Martin, et al. (2021)
• Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma — K. Pillai, J. Akhter, et al. (2013)
• Anticancer effect of bromelain with and without cisplatin or 5-FU on malignant peritoneal mesothelioma cells — K. Pillai, A. Ehteda, et al. (2014)
• EF24 and RAD001 potentiates the anticancer effect of platinum-based agents in human malignant pleural mesothelioma (MSTO-211H) cells and protects nonmalignant mesothelial (MET-5A) cells — H.I. Onen, A. Yilmaz, et al. (2015)

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