**5. Conclusions**

The results of this study demonstrate that **B** induced caspase dependent apoptosis and autophagy in Caco2 cells via activating the ROS/JNK signaling pathway in vitro. In addition, **B** stabilized the microtubule dynamics and disrupted cell cycle progression by inducing G2/M phase arrest. Moreover, **B** exhibited synergism with known chemotherapeutic 5FU and novel compound D on the CRC cells. Together, **B** shows great potential as a novel drug candidate that can be used for further research to develop into an anticancer therapeutic against CRC.

**Supplementary Materials:** The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers15020489/s1, Table S1: Nucleotide sequence of EL000327. Figure S1: B induces G2/M phase arrest in the CRC cells; Figure S2: **B** induces nuclei condensation in the CRC cells; Figure S3: **B** induces apoptosis in CRC cells; Figure S4: **B** decreased apoptosis in the Caco2 cells in the presence of ROS and JNK inhibitors; Figure S5: **B** modulated cell cycle related protein expressions and anti-apoptotic protein Bcl-XL; Figure S6: 1H NMR spectrum of Libertellenone T (**B)** in MeOD; Figure S7: 13C NMR spectrum of Libertellenone T (**B)** in MeOD; Figure S8: Percentage purity of Libertellenone T (**B**); Figure S9: The raw data of Western blotting.

**Author Contributions:** H.K. and C.D.B.G. conceived and designed the experiments. C.D.B.G., S.-Y.P., M.V., R.Z., S.P., Y.Y. and ˙ I.T. performed the experiments. J.-S.H. contributed the materials. J.-H.K. and S.-J.N. isolated the single compounds. C.D.B.G. and H.K. analyzed the data and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the National Research Foundation of Korea grant (NRF-2020R1C1C1007832) funded by the Korean government (MSIP).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** All of the data generated or analyzed during this study are included in the published article and its Supplementary files.

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

#### **References**


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