Elucidation of the mechanism underlying apoptosis induced by vitamin K3 analogs in a human leukemia-derived cell line WCRJ 2026; 13 : e3012
DOI: 10.32113/wcrj_20263_3012

  Topic: Cancer biology, Haematological oncology     Category: Original article

Suzuki M. Department of Pharmacy, Toho University Medical Center Omori Hospital, Ota-ku, Tokyo, Japan , Watanabe K. Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Funabashi, Chiba, Japan , Kato K. Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Funabashi, Chiba, Japan , Kano H. Laboratory of Clinical Medicine, Nihon University School of Pharmacy, Funabashi, Chiba, Japan , Asami S. Abstract Objective: Thioether analogs of vitamin K3 (VK3) promote the generation of reactive oxygen species (ROS) and enhance the expression of the apoptosis-inducing receptor Fas and its ligand, thereby inducing apoptosis through activation of mitogen-activated protein kinase (MAPK) and caspase-3. They can also induce apoptosis without generating ROS by maintaining phosphorylation via inhibition of mitochondrial or tyrosine and serine/threonine phosphatases involved in intracellular signal transduction. Moreover, VK3 analogs have been shown to upregulate death receptor 5 (DR5) and induce apoptosis in human leukemia-derived cells through the intracellular DR signaling pathway. In this study, we aimed to investigate the effect of the VK3 analog 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone (CPD5) on the expression of factors acting further upstream in this signaling pathway.

Materials and Methods: Apoptosis induction in human leukemia-derived cells following CPD5 treatment was examined by assessing intracellular protein expression levels using Western blotting. The analyzed proteins were factors involved in apoptosis signaling upstream of DR5.

Results: Treatment with CPD5 (10 μM) activated caspase-3 and caspase-8 and increased the expression of DR5. Further investigation of upstream signaling revealed elevated levels of tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL), which acts on death receptors. Expression of the TRAIL-cleaving enzyme was also increased.

Conclusions: These findings indicate that CPD5 acts on the TRAIL-cleaving enzyme in leukemia-derived cells, leading to the excessive release of soluble TRAIL (sTRAIL) and subsequent apoptosis via DR5. By elucidating its upstream effects and site of action, CPD5 can be proposed as a potential anti-tumor agent.

To cite this article Suzuki M. Department of Pharmacy, Toho University Medical Center Omori Hospital, Ota-ku, Tokyo, Japan , Watanabe K. Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Funabashi, Chiba, Japan , Kato K. Laboratory of Environmental Toxicology and Carcinogenesis, Nihon University School of Pharmacy, Funabashi, Chiba, Japan , Kano H. Laboratory of Clinical Medicine, Nihon University School of Pharmacy, Funabashi, Chiba, Japan , Asami S. Elucidation of the mechanism underlying apoptosis induced by vitamin K3 analogs in a human leukemia-derived cell line

WCRJ 2026; 13 : e3012
DOI: 10.32113/wcrj_20263_3012

Publication History

Submission date: 12 Aug 2025

Revised on: 30 Oct 2025

Accepted on: 03 Mar 2026

Published online: 25 Mar 2026

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