Nicaraven induces programmed cell death by distinct mechanisms according to the expression levels of Bcl-2 and poly (ADP-ribose) glycohydrolase in cancer cells

Lina Abdelghany; Tsuyoshi Kawabata; Shinji Goto; Keiichi Jingu; Tao-Sheng Li

Translational Oncology (Dec 2022)

Nicaraven induces programmed cell death by distinct mechanisms according to the expression levels of Bcl-2 and poly (ADP-ribose) glycohydrolase in cancer cells

Lina Abdelghany,
Tsuyoshi Kawabata,
Shinji Goto,
Keiichi Jingu,
Tao-Sheng Li

Affiliations

Lina Abdelghany: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Tsuyoshi Kawabata: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Shinji Goto: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Keiichi Jingu: Department of Radiation Oncology, Graduate School of Medicine, Tohoku University, Sendai, Japan
Tao-Sheng Li: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; Corresponding author at: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

Journal volume & issue: Vol. 26
p. 101548

Abstract

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The PARP-1 expression level and poly (ADP-ribosyl)ation activity in cancer markedly affect the therapeutic outcome. Nicaraven, a free radical scavenger has been found to inhibit PARP, but the effect on cancer cells is still unclear. In this study, we investigated the potential role and molecular mechanism of nicaraven on cancer cells. Using U937 lymphoma cells and HCT-8 colorectal cancer cells, we found that nicaraven moderately reduced the cell viability of both cells in a dose-dependent manner. Interestingly, nicaraven significantly induced apoptosis of U937 cells that are dominantly expressing Bcl-2 but induced PAR-dependent cell death (parthanatos) of HCT-8 cells that are highly expressing poly (ADP-ribose) glycohydrolase (PARG). Based on our data, nicaraven seems to induce programmed cell death through distinct mechanisms, according to the expression levels of Bcl-2 and PARG in cancer cells.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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