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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

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Abstract

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-κB 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-κB 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-κB activities with the low IC50 concentration of 5.82 ± 1.6, 6.74 ± 1.2, and 10.7 ± 1.5 μM 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 ± 1.9, 85.9 ± 2.7, and 97.4 ± 1.5 μM, respectively. These results correlate with the relatively high IC50 concentration of 16.3 ± 1.76, 7.67 ± 0.78, and 10.7 ± 0.96 μM 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 ± 0.02 and 0.08 ± 0.01 μM, respectively, compared to the healthy, human embryonic kidney (HEK-293) cells with the high IC50 concentration of 54.7 ± 1.43 μM. In summary, the affinity of DAPG with proteins are in the order of MMP-2 > MMP-9 > NF-κB > 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.

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Abbreviations

Bax:

Bcl-2-associated X-protein

Bcl-2:

B-cell lymphoma 2

DCF-2, 7:

Dichlorofluorescein

DMEM:

Dulbecco’s modified eagle medium

FBS:

Fetal bovine serum

LPS:

Lipopolysaccharide

NF-κB:

Nuclear factor κB

RPMI:

Roswell Park Memorial Institute

MMP:

Matrix metalloproteinase

PVDF:

Polyvinylidene fluoride

BSA:

Bovine serum albumin

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Acknowledgments

The joint University Grant Commission-Council for Scientific and Industrial Research (joint UGC-CSIR), Government of India, New Delhi, through a research fellowship to Ms. V. Veena, the financial support from the Department of Biotechnology (DBT), New Delhi, and the University Grants Commission-Special Assistance Programme (UGC-SAP) co-ordinated by Prof. Dr. N. Sakthivel are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biotechnology, School of Life Science, Pondicherry University, Pondicherry, 605014, India

    Vijay Kumar Veena, Kamaraj Kennedy & N. Sakthivel

  2. Centre for Bioinformatics, School of Life Science, Pondicherry University, Pondicherry, India

    Pragna Lakshmi & R. Krishna

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  1. Vijay Kumar Veena
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  2. Kamaraj Kennedy
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  3. Pragna Lakshmi
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Correspondence to N. Sakthivel.

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Veena, V.K., Kennedy, K., Lakshmi, P. et al. 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. Mol Cell Biochem 414, 47–56 (2016). https://doi.org/10.1007/s11010-016-2657-6

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