**5. Conclusions**

In this study, we analyzed the effect of JI017 on human lung cancer cells. JI017 treatment induced the activation of autophagy signaling by increasing the generation of intracellular ROS. As a result, JI017 treatment decreased cell viability and caused apoptotic cell death in lung cancer cells. These results support JI017 as a favorable candidate drug for the treatment of human lung cancer.

**Author Contributions:** J.M.K. carried out the experiments and drafted the manuscript. M.J.K., Y.-J.C. and S.Y.L. revised the research and manuscript and assisted in the research work. J.M.K., M.J.K., Y.-J.C., J.W.C. and S.Y.L. contributed to the design of this study and performed the data analysis. S.Y., J.-H.K., Y.-K.J., J.-Y.I. and J.W.C. assisted with the use of the software. Y.C.S. and S.-G.K. guided the research and revised and submitted the manuscript. S.-G.K. supervised the experiments and corrected the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. NRF-2020R1A5A2019413).

**Institutional Review Board Statement:** The animal study protocol was approved by the Kyung Hee University Institutional Animal Care and Use Committee (KHSASP-20-250).

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** All data and materials are contained and described within the manuscript.

**Acknowledgments:** We thank our colleagues from the Laboratory of Prevention Medicine for protocol assistance and useful discussions.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **Abbreviations**

*Ac*, *Aconitum carmichaeli*; *Ag*, *Angelica gigas*; BHT, butylated hydroxytoluene; DAB, 3,3- -Diaminobenzidine; DMSO, dimethyl sulfoxide; EDTA, ethylenediaminetetraacetic acid; FACS, fluorescenceactivated cell sorter; FBS, fetal bovine serum; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IHC, immunohistochemistry; MDA, malondialdehyde; NSCLC, non-small-cell lung cancer; PARP, poly (ADP-ribose) polymerase; PBS, phosphate-buffered saline; PI, propidium iodide; PMSF, phenylmethylsulfonyl fluoride; PUFAs, polyunsaturated fatty acids; ROS, reactive oxygen species; SCLC, small-cell lung cancer; SD, standard deviation; SDS, sodium dodecyl sulphate, TBA, thiobarbituric acid; *Zo*, *Zingiber officinale Roscoe*.

#### **References**


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