1-\[2-(2-Methoxyphenylamino)ethylamino\]-3-(naphthalene-1- yloxy)propan-2-ol may be a promising anticancer drug

Our plain-English summary of 1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1- yloxy)propan-2-ol may be a promising anticancer drug, by T. Nishizaki, T. Kanno, A. Tsuchiya, et al (Molecules, 2014).

The study

• Authors: T. Nishizaki, T. Kanno, A. Tsuchiya, Y. Kaku, T. Shimizu, A. Tanaka
• Journal: Molecules
• Published: 2014;19(12):21462-72
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We have originally synthesized the naftopidil analogue 1-[2-(2-methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol (HUHS 1015) as a new anticancer drug. HUHS1015 induces cell death in a wide variety of human cancer cell lines originated from malignant pleural mesothelioma, lung cancer, hepatoma, gastric cancer, colorectal cancer, bladder cancer, prostate cancer, and renal cancer. HUHS1015-induced cell death includes necrosis (necroptosis) and apoptosis, and the underlying mechanism differs depending upon cancer cell types. HUHS1015 effectively suppresses tumor growth in mice inoculated with NCI-H2052, MKN45, or CW2 cells, with a potential similar to or higher than that of currently used anticancer drugs. Here we show how HUHS1015 might offer brilliant hope for cancer therapy.

In plain English

This article is a review in which the authors summarized their own laboratory work on HUHS1015, one of 21 compounds they made by modifying naftopidil, a drug used for benign prostate enlargement and high blood pressure. The research used human cancer cell lines and mice, not patients, and did not study asbestos exposure. Among the 21 compounds tested on four malignant pleural mesothelioma cell lines, HUHS1015 had the strongest effect. It also induced cell death in lung, liver, gastric, colorectal, bladder, prostate and kidney cancer cell lines. After 12 hours, 61%, 69%, 37% and 58% of cells in the mesothelioma lines NCI-H28, NCI-H2052, NCI-H2452 and MSTO-211H showed a marker of programmed cell death (apoptosis). The authors reported both necrosis and apoptosis, by mechanisms that differed between cell types. In mice carrying NCI-H2052 mesothelioma cells, survival two months after treatment was 100% with HUHS1015 and 30% with paclitaxel. In mice carrying gastric cancer cells, irinotecan suppressed tumor growth much more than HUHS1015. The authors concluded that HUHS1015 could be developed as a new anticancer drug.

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: Review of the authors' own laboratory research: cell-line experiments and mouse xenograft (implanted human tumor) experiments with a newly synthesized compound
• Who was studied: Human cancer cell lines: the malignant pleural mesothelioma lines NCI-H28, NCI-H2052, NCI-H2452 and MSTO-211H, plus lung, hepatoma, gastric, colorectal, bladder, prostate and renal cancer lines. Also mice implanted with NCI-H2052 (mesothelioma), MKN45 (gastric) or CW2 (colorectal) cells. The number of mice is not given.
• Exposure: No asbestos exposure was studied. The exposure was the experimental compound HUHS1015, one of 21 naftopidil analogues, compared in mice with naftopidil, paclitaxel, cisplatin and irinotecan.
• Main results:
  • Of the 21 naftopidil analogues tested on the mesothelioma cell lines, HUHS1015 had the most beneficial effect.
  • After a 12-hour treatment, TUNEL-positive (apoptotic) cells reached 61%, 69%, 37% and 58% of total cells in the NCI-H28, NCI-H2052, NCI-H2452 and MSTO-211H mesothelioma cell lines respectively.
  • The authors reported that HUHS1015 induced both necrosis and apoptosis in a variety of cancer cell lines.
  • In mice inoculated with NCI-H2052 mesothelioma cells, survival two months after treatment was 100% with HUHS1015 and 30% with paclitaxel.
  • In mice inoculated with MKN45 gastric cancer cells, irinotecan suppressed tumor growth much more strongly than HUHS1015. HUHS1015 was about equal to cisplatin and stronger than paclitaxel and naftopidil.
  • In mice inoculated with MKN45 cells, survival at 33 days of treatment was 100% with HUHS1015, compared with 43% for cisplatin, 71% for irinotecan and 86% for paclitaxel.
  • In mice inoculated with CW2 colorectal cancer cells, survival at 33 days of treatment with HUHS1015 was 100%.
  • The authors reported no remarkable body weight loss in the mice, and blood tests showed no liver or kidney dysfunction.
• The authors' conclusion: The authors concluded that HUHS1015 induces necrosis and apoptosis in a wide variety of cancer cells, suppressed tumor growth in mice with fewer side effects, and could be developed as a new anticancer drug.
• Limitations the authors state:
  • The authors stated it is unknown whether HUHS1015 induces endoplasmic reticulum stress or how it activates caspase-4.

Topics

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

Related studies

• 1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol as a potential anticancer drug — T. Kanno, A. Tanaka, et al. (2013)
• Newly synthesized anticancer drug HUHS1015 is effective on malignant pleural mesothelioma — Y. Kaku, H. Nagaya, et al. (2014)
• AMP converted from intracellularly transported adenosine upregulates p53 expression to induce malignant pleural mesothelioma cell apoptosis — Y. Nogi, T. Kanno, et al. (2012)
• Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• Cephalomannine as in vitro and in vivo anticancer agent in mesothelioma cells: mechanisms of action — F. Morani, I. Dell'Anno, et al. (2025)
• Abrogating G₂/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma — P. Indovina, E. Marcelli, et al. (2014)

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