A small compound KJ-28d enhances the sensitivity of non-small cell lung cancer to radioand chemotherapy

Hwani Ryu, Hyo Jeong Kim, Jie Young Song, Sang Gu Hwang, Jae Sung Kim, Joon Kim, Thi Hong Nhung Bui, Hyun Kyung Choi, Jiyeon Ahn

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number6026
JournalInternational journal of molecular sciences
Volume20
Issue number23
DOIs
Publication statusPublished - 2019 Dec 1

Keywords

  • Chemotherapy
  • Combination therapy
  • DNA damage
  • Non-small cell lung cancer
  • Poly (ADP-ribose) polymerase inhibitor
  • Radiotherapy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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