Limits...
Targeting procaspase-3 with WF-208, a novel PAC-1 derivative, causes selective cancer cell apoptosis.

Wang F, Liu Y, Wang L, Yang J, Zhao Y, Wang N, Cao Q, Gong P, Wu C - J. Cell. Mol. Med. (2015)

Bottom Line: Caspase-3 is a critical effector caspase in apoptosis cascade, and is often over-expressed in many cancer tissues.WF-208 also showed greater antitumour activity than PAC-1 in murine xenograft model.In conclusion, we have discovered WF-208 as a promising procaspase-3 activating compound, with higher activity and higher cell selectivity than PAC-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China.

No MeSH data available.


Related in: MedlinePlus

Cytotoxicity of PAC-1 and WF-208 against cancerous cells and normal cells. (A) The IC50 of PAC-1 and WF-208 in various cancerous cells. (B) The IC50 of PAC-1 and WF-208 in various normal cells. (C) The cytotoxicity of WF-208 and PAC-1 against mouse primary cortical neuron cells. (D) The mean of IC50 in cancerous cells and normal cells and selection index (SI) of WF-208.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4549042&req=5

fig03: Cytotoxicity of PAC-1 and WF-208 against cancerous cells and normal cells. (A) The IC50 of PAC-1 and WF-208 in various cancerous cells. (B) The IC50 of PAC-1 and WF-208 in various normal cells. (C) The cytotoxicity of WF-208 and PAC-1 against mouse primary cortical neuron cells. (D) The mean of IC50 in cancerous cells and normal cells and selection index (SI) of WF-208.

Mentions: The cytotoxicity of WF-208 was measured with MTT method using the human malignant cell lines (leukaemia, lung cancer, hepatoma, colon carcinoma, prostate carcinoma, breast carcinoma, gastric cancer, breast cancer, glioma, gallbladder carcinoma) and normal human cells after the treatment with different concentrations of WF-208 for 72 hrs. WF-208 displayed more cytotoxicity against tumour cells than PAC-1, with IC50 values ranging from 0.08 to 12.85 μM (Fig.3A and B). The overall mean IC50 value of WF 208 in the fifteen malignant cell lines was 1.66 μM (Fig.3C), which was an approximate 20-fold increase compared with PAC-1. In contrast, the sensitivity of the human primary cells and the human normal cell lines to WF-208 were much lower. The IC50 value for WF-208 on PBL is 742.62 μM, which was much higher than that for PAC-1. The mean IC50 value for WF-208 on three different normal cells was 215.79 μM, which was significantly higher than that for PAC-1 (P = 0.022). In addition, because of previously reported neurotoxicity of PAC-1 in vitro and in vivo15,17, the neurotoxicity of WF-208 was also investigated. In this study, the cytotoxicity of WF-208 (IC50 = 96.18 μM) in mouse primary cortical cell was lower than PAC-1 (IC50 = 50.10 μM; Fig.3D). In summary, these results suggest a higher selective cytotoxicity against human malignant cells of WF-208.


Targeting procaspase-3 with WF-208, a novel PAC-1 derivative, causes selective cancer cell apoptosis.

Wang F, Liu Y, Wang L, Yang J, Zhao Y, Wang N, Cao Q, Gong P, Wu C - J. Cell. Mol. Med. (2015)

Cytotoxicity of PAC-1 and WF-208 against cancerous cells and normal cells. (A) The IC50 of PAC-1 and WF-208 in various cancerous cells. (B) The IC50 of PAC-1 and WF-208 in various normal cells. (C) The cytotoxicity of WF-208 and PAC-1 against mouse primary cortical neuron cells. (D) The mean of IC50 in cancerous cells and normal cells and selection index (SI) of WF-208.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549042&req=5

fig03: Cytotoxicity of PAC-1 and WF-208 against cancerous cells and normal cells. (A) The IC50 of PAC-1 and WF-208 in various cancerous cells. (B) The IC50 of PAC-1 and WF-208 in various normal cells. (C) The cytotoxicity of WF-208 and PAC-1 against mouse primary cortical neuron cells. (D) The mean of IC50 in cancerous cells and normal cells and selection index (SI) of WF-208.
Mentions: The cytotoxicity of WF-208 was measured with MTT method using the human malignant cell lines (leukaemia, lung cancer, hepatoma, colon carcinoma, prostate carcinoma, breast carcinoma, gastric cancer, breast cancer, glioma, gallbladder carcinoma) and normal human cells after the treatment with different concentrations of WF-208 for 72 hrs. WF-208 displayed more cytotoxicity against tumour cells than PAC-1, with IC50 values ranging from 0.08 to 12.85 μM (Fig.3A and B). The overall mean IC50 value of WF 208 in the fifteen malignant cell lines was 1.66 μM (Fig.3C), which was an approximate 20-fold increase compared with PAC-1. In contrast, the sensitivity of the human primary cells and the human normal cell lines to WF-208 were much lower. The IC50 value for WF-208 on PBL is 742.62 μM, which was much higher than that for PAC-1. The mean IC50 value for WF-208 on three different normal cells was 215.79 μM, which was significantly higher than that for PAC-1 (P = 0.022). In addition, because of previously reported neurotoxicity of PAC-1 in vitro and in vivo15,17, the neurotoxicity of WF-208 was also investigated. In this study, the cytotoxicity of WF-208 (IC50 = 96.18 μM) in mouse primary cortical cell was lower than PAC-1 (IC50 = 50.10 μM; Fig.3D). In summary, these results suggest a higher selective cytotoxicity against human malignant cells of WF-208.

Bottom Line: Caspase-3 is a critical effector caspase in apoptosis cascade, and is often over-expressed in many cancer tissues.WF-208 also showed greater antitumour activity than PAC-1 in murine xenograft model.In conclusion, we have discovered WF-208 as a promising procaspase-3 activating compound, with higher activity and higher cell selectivity than PAC-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China.

No MeSH data available.


Related in: MedlinePlus