TY - JOUR
T1 - Thymoquinone poly (lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential
AU - Ravindran, Jayaraj
AU - Nair, Hareesh B.
AU - Sung, Bokyung
AU - Prasad, Sahdeo
AU - Tekmal, Rajeshwar R.
AU - Aggarwal, Bharat B.
N1 - Funding Information:
We thank Walter Pagel for carefully proofreading the manuscript and providing valuable comments. Dr. Aggarwal is the Ransom Horne, Jr., Professor of Cancer Research. This work was supported by a grant from the Clayton Foundation for Research (B.B.A.), a core grant from the National Institutes of Health (CA-16 672), a program project grant from National Institutes of Health ( NIH CA-124787-01A2 ), and grant from Center for Targeted Therapy of M.D. Anderson Cancer Center .
PY - 2010/6
Y1 - 2010/6
N2 - Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy confirmed particle diameter between 150 and 200. nm. Electrophoretic gel shift mobility assay showed that TQ nanoparticles (NP) were more active than TQ in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), those are markers of cell proliferation, metastasis and angiogenesis, respectively. TQ-NP were also more potent than TQ in suppressing proliferation of colon cancer, breast cancer, prostate cancer, and multiple myeloma cells. Esterase staining for plasma membrane integrity revealed that TQ-NP were more potent than TQ in sensitizing leukemic cells to TNF- and paclitaxel-induced apoptosis. Overall our results demonstrate that encapsulation of TQ into nanoparticles enhances its anti-proliferative, anti-inflammatory, and chemosensitizing effects.
AB - Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy confirmed particle diameter between 150 and 200. nm. Electrophoretic gel shift mobility assay showed that TQ nanoparticles (NP) were more active than TQ in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), those are markers of cell proliferation, metastasis and angiogenesis, respectively. TQ-NP were also more potent than TQ in suppressing proliferation of colon cancer, breast cancer, prostate cancer, and multiple myeloma cells. Esterase staining for plasma membrane integrity revealed that TQ-NP were more potent than TQ in sensitizing leukemic cells to TNF- and paclitaxel-induced apoptosis. Overall our results demonstrate that encapsulation of TQ into nanoparticles enhances its anti-proliferative, anti-inflammatory, and chemosensitizing effects.
KW - Apoptosis
KW - Inflammation
KW - NF-κB
KW - Nanoparticles
KW - Thymoquinone
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U2 - 10.1016/j.bcp.2010.01.023
DO - 10.1016/j.bcp.2010.01.023
M3 - Article
C2 - 20105430
AN - SCOPUS:77950086914
SN - 0006-2952
VL - 79
SP - 1640
EP - 1647
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 11
ER -