*Article* **A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radioand Chemotherapy**

**Hwani Ryu 1,2, Hyo Jeong Kim <sup>1</sup> , Jie-Young Song <sup>1</sup> , Sang-Gu Hwang <sup>1</sup> , Jae-Sung Kim <sup>1</sup> , Joon Kim <sup>2</sup> , Thi Hong Nhung Bui <sup>3</sup> , Hyun-Kyung Choi 3,\* and Jiyeon Ahn 1,\***


Received: 10 October 2019; Accepted: 29 November 2019; Published: 29 November 2019

**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.

**Keywords:** poly (ADP-ribose) polymerase inhibitor; non-small cell lung cancer; DNA damage; radiotherapy; chemotherapy; combination therapy
