Page 64 - I. Chemical biology and drug discovery

[I. Chemical biology and drug discovery-35]

Anti-cancer effects of the root of TK in human non-small cell

lung cancer cells with resistance to epidermal growth factor

receptor-tyrosine kinase inhibitors

Hyun-Ji Park¹, Shin-Hyung Park¹˙*

¹Department of Pathology, College of Korean Medicine, Dongeui University, Busan 47227, Korea

Although epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) has become the standard treatment
for non-small cell lung cancer (NSCLC), acquired resistance to these drugs remains a major obstacle for managing
NSCLC. This study explored the anti-cancer effects of the root of TK in NSCLC cells with EGFR TKIs resistance. We

first established erlotinib-resistant PC9 (PC9/ER) and gefitinib-resistant PC9 (PC9/GR) cell lines using a dose-
escalating maintenance of drugs in PC9 cells. We also used H1975 cell line (L858R/T790M) as the EGFR-TKI resistant

cell line. Our results showed that ethanol extract of TK (ETK) suppressed the cell proliferation in EGFR-TKI resistant
cell lines. In addition, ETK enhanced the sub-G1 DNA content, annexin V-positive cell population as well as chromatin

condensation. The expression of cleaved PARP and cleaved caspase-3 was also increased by ETK. These findings
demonstrate that ETK induced apoptosis in EGFR TKI-resistant NSCLC cell lines. Furthermore, the activities of general

activators of cancer cell proliferation were significantly decreased by ETK in H1975 cells. In conclusion, the current
study suggests the potential use of TK for managing the advanced NSCLC with EGFR-TKIs resistance (NRF-

2019R1F1A1059588).