- Title
-
A Terphenyllin Derivative CHNQD-00824 from the Marine Compound Library Induced DNA Damage as a Potential Anticancer Agent
- Authors
- Cao, X.Z., Zhang, B.Q., Wang, C.F., Yin, J.N., Haider, W., Said, G., Wei, M.Y., Lu, L.
- Source
- Full text @ Mar. Drugs
Marine natural products approved as the anticancer drugs. |
The discovery and biological activity research of compound CHNQD-00824. |
Natural product compounds 1–4 and terphenyllin derivatives 5–11 |
The cytotoxicity data of compounds 1–11. (A) The inhibitory activity of compounds 1–11 against BT549 cell line. Adriamycin as a positive control. (B) CHNQD-00824 evaluated in thirteen different tumor cells. n = 3 biological replicate samples. |
CHNQD-00824 inhibited the proliferation and migration of BT549 cells. (A,B) CHNQD-00824 inhibited the colony formation of BT549 cells. The BT549 cells were treated with CHNQD-00824 for 13 d, then the clones were photographed and counted. (C) Growth curves of BT549 cells treated with CHNQD-00824 (5 μM) and DMSO. (D,E) The scratch assay of BT549 cells after treatment with CHNQD-00824 for 12 h and 24 h. Scale bar, 100 μm. The data shown are the mean ± SD (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 and ns, nonsignificant). n = 3 biological replicate samples. |
CHNQD-00824-induced apoptosis and cell cycle arrest in BT549 cells. (A,C) Flow cytometry analysis of cell cycle analysis on BT549 cells after treatment with CHNQD-00824 for 24 h. (B,D) Flow cytometry analysis of BT549 cells stained with the Annexin V/FITC-PI double staining solution after treatment with CHNQD-00824 for 24 h. (E) Effect of CHNQD-00824 on apoptosis-related proteins. BT549 cells were treated with CHNQD-00824 (0–8 μM) for 24 h, then cells were harvested and proteins were separated by electrophoresis on SDS-PAGE. Western blotting analysis were performed to detect the expression of cleaved-PARP, cleaved-caspase-3, Cyto-c and BAD. (F) Histogram shows the relative abundance of apoptosis-related proteins compared with the control group. The data shown are the mean ± SD (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, and ns, nonsignificant). n = 3 biological replicate samples. |
CHNQD-00824-induced DNA damage. (A) Effect of CHNQD-00824 on DNA damage marker proteins. BT549 cells were treated with CHNQD-00824 (0–8 μM) for 24 h, then cells were harvested and proteins were separated by electrophoresis on SDS-PAGE. Western blotting analysis were performed to detect the expression of γH2AX. (B) Histogram shows the relative abundance of γH2AX compared with the control group. (C,D) AO staining of zebrafish embryos at 48 hpf. When development reached 24 hpf, zebrafish embryos were treated with CHNQD-00824 (0–15 μM) to 48 hpf. AO staining was then performed. Scale bar, 1 mm. The data shown are the mean ± SD (** p < 0.01, *** p < 0.001, **** p < 0.0001). n = 3 biological replicate samples. |
CHNQD-00824 inhibited tumor growth in zebrafish. (A) Zebrafish model of liver cancer. When development reached 3 dpf, zebrafish were treated with DOX (60 mg/L) and CHNQD-00824 (1.25–5 μM) to 7 dpf. Sorafenib as positive control. (B) Tumor size in zebrafish was measured by photography at 7 dpf. The data shown are the mean ± SD (**** p < 0.0001, ## p < 0.01, #### p < 0.0001, and ns, nonsignificant). n = 3 biological replicate samples. |