Cargando…

A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy

We previously reported on a poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor N-(3-(hydroxycarbamoyl)phenyl)carboxamide (designated KJ-28d), which increased the death of human ovarian cancer BRCA1-deficient SNU-251 cells. In the present study, we further investigated the antitumor activities of KJ-2...

Descripción completa

Detalles Bibliográficos
Autores principales: Ryu, Hwani, Kim, Hyo Jeong, Song, Jie-Young, Hwang, Sang-Gu, Kim, Jae-Sung, Kim, Joon, Bui, Thi Hong Nhung, Choi, Hyun-Kyung, Ahn, Jiyeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928747/
https://www.ncbi.nlm.nih.gov/pubmed/31795418
http://dx.doi.org/10.3390/ijms20236026
_version_ 1783482543792717824
author Ryu, Hwani
Kim, Hyo Jeong
Song, Jie-Young
Hwang, Sang-Gu
Kim, Jae-Sung
Kim, Joon
Bui, Thi Hong Nhung
Choi, Hyun-Kyung
Ahn, Jiyeon
author_facet Ryu, Hwani
Kim, Hyo Jeong
Song, Jie-Young
Hwang, Sang-Gu
Kim, Jae-Sung
Kim, Joon
Bui, Thi Hong Nhung
Choi, Hyun-Kyung
Ahn, Jiyeon
author_sort Ryu, Hwani
collection PubMed
description We previously reported on a poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor N-(3-(hydroxycarbamoyl)phenyl)carboxamide (designated KJ-28d), which increased the death of human ovarian cancer BRCA1-deficient SNU-251 cells. In the present study, we further investigated the antitumor activities of KJ-28d in BRCA-proficient non-small cell lung cancer (NSCLC) cells to expand the use of PARP inhibitors. KJ-28d significantly inhibited the growth of NSCLC cells in vitro and in vivo, and induced DNA damage and reactive oxygen species in A549 and H1299 cells. Combined treatment with KJ-28d and ionizing radiation led to increased DNA damage responses in A549 and H1299 cells compared to KJ-28d or ionizing radiation alone, resulting in apoptotic cell death. Moreover, the combination of KJ-28d plus a DNA-damaging therapeutic agent (carboplatin, cisplatin, paclitaxel, or doxorubicin) synergistically inhibited cell proliferation, compared to either drug alone. Taken together, the findings demonstrate the potential of KJ-28d as an effective anti-cancer therapeutic agent for BRCA-deficient and -proficient cancer cells. KJ-28d might have potential as an adjuvant when used in combination with radiotherapy or DNA-damaging agents, pending further investigations.
format Online
Article
Text
id pubmed-6928747
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-69287472019-12-26 A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy Ryu, Hwani Kim, Hyo Jeong Song, Jie-Young Hwang, Sang-Gu Kim, Jae-Sung Kim, Joon Bui, Thi Hong Nhung Choi, Hyun-Kyung Ahn, Jiyeon Int J Mol Sci Article We previously reported on a poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor N-(3-(hydroxycarbamoyl)phenyl)carboxamide (designated KJ-28d), which increased the death of human ovarian cancer BRCA1-deficient SNU-251 cells. In the present study, we further investigated the antitumor activities of KJ-28d in BRCA-proficient non-small cell lung cancer (NSCLC) cells to expand the use of PARP inhibitors. KJ-28d significantly inhibited the growth of NSCLC cells in vitro and in vivo, and induced DNA damage and reactive oxygen species in A549 and H1299 cells. Combined treatment with KJ-28d and ionizing radiation led to increased DNA damage responses in A549 and H1299 cells compared to KJ-28d or ionizing radiation alone, resulting in apoptotic cell death. Moreover, the combination of KJ-28d plus a DNA-damaging therapeutic agent (carboplatin, cisplatin, paclitaxel, or doxorubicin) synergistically inhibited cell proliferation, compared to either drug alone. Taken together, the findings demonstrate the potential of KJ-28d as an effective anti-cancer therapeutic agent for BRCA-deficient and -proficient cancer cells. KJ-28d might have potential as an adjuvant when used in combination with radiotherapy or DNA-damaging agents, pending further investigations. MDPI 2019-11-29 /pmc/articles/PMC6928747/ /pubmed/31795418 http://dx.doi.org/10.3390/ijms20236026 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ryu, Hwani
Kim, Hyo Jeong
Song, Jie-Young
Hwang, Sang-Gu
Kim, Jae-Sung
Kim, Joon
Bui, Thi Hong Nhung
Choi, Hyun-Kyung
Ahn, Jiyeon
A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy
title A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy
title_full A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy
title_fullStr A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy
title_full_unstemmed A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy
title_short A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy
title_sort small compound kj-28d enhances the sensitivity of non-small cell lung cancer to radio- and chemotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928747/
https://www.ncbi.nlm.nih.gov/pubmed/31795418
http://dx.doi.org/10.3390/ijms20236026
work_keys_str_mv AT ryuhwani asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT kimhyojeong asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT songjieyoung asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT hwangsanggu asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT kimjaesung asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT kimjoon asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT buithihongnhung asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT choihyunkyung asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT ahnjiyeon asmallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT ryuhwani smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT kimhyojeong smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT songjieyoung smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT hwangsanggu smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT kimjaesung smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT kimjoon smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT buithihongnhung smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT choihyunkyung smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy
AT ahnjiyeon smallcompoundkj28denhancesthesensitivityofnonsmallcelllungcancertoradioandchemotherapy