Anti-leukemic, anti-lung, and anti-breast cancer potential of the microbial polyketide 2, 4-diacetylphloroglucinol (DAPG) and its interaction with the metastatic proteins than the antiapoptotic Bcl-2 proteins

作者：Veena Vijay Kumar; Kennedy Kamaraj; Lakshmi Pragna; Krishna R; Sakthivel N^*

来源：Molecular and Cellular Biochemistry, 2016, 414(1-2): 47-56.

DOI：10.1007/s11010-016-2657-6

• DAPG
• Metastatic proteins
• Antiapoptotic Bcl-2 family members
• In silico interaction studies
• In vitro validation studies

The microbial polyketide, 2, 4-diacetylphloroglucinol (DAPG), exhibited a broad-spectrum of anti-leukemic, anti-lung, and anti-breast cancer properties. The aim of the present investigation was to study the interactive potentials of DAPG with the metastatic proteins such as MMP-2, MMP-9, and NF-kappa B and antiapoptotic Bcl-2 family proteins such as Bcl-2, Bcl-w, and Bcl-xL through in silico interaction and in vitro studies. The in silico modeling predicted high interactions of DAPG with the metastatic proteins, especially MMP-2, MMP-9, and NF-kappa B with the glide score of -7.028, -6.304, and -5.231, respectively. Similarly, the DAPG had weak interactions with the antiapoptotic Bcl-2, Bcl-w, and Bcl-xL with the glide score of -4.505, -3.839, and -4.003, respectively. The interaction studies further revealed the inhibition of MMP-2, MMP-9, and NF-kappa B activities with the low IC50 concentration of 5.82 +/- A 1.6, 6.74 +/- A 1.2, and 10.7 +/- A 1.5 mu M respectively, in the presence of DAPG. Similarly, DAPG inhibited the Bcl-2, Bcl-xL and Bcl-w activities with the high IC50 concentration of 29.8 +/- A 1.9, 85.9 +/- A 2.7, and 97.4 +/- A 1.5 mu M, respectively. These results correlate with the relatively high IC50 concentration of 16.3 +/- A 1.76, 7.67 +/- A 0.78, and 10.7 +/- A 0.96 mu M in the Bcl-2-overexpressing HL-60, K562 and Raji leukemic cells than the metastatic A549 and MDA MB-231 cancer cells with the low IC50 concentration of 0.06 +/- A 0.02 and 0.08 +/- A 0.01 mu M, respectively, compared to the healthy, human embryonic kidney (HEK-293) cells with the high IC50 concentration of 54.7 +/- A 1.43 mu M. In summary, the affinity of DAPG with proteins are in the order of MMP-2 > MMP-9 > NF-kappa B > Bcl-2 > Bcl-xL > Bcl-w. Results presented in this study confirmed the high interaction of DAPG with the metastatic proteins than the antiapoptotic Bcl-2 family proteins.

• 出版日期2016-3
• 单位上海生物信息技术研究中心