title: Enhanced colon cancer chemoprevention of curcumin by nanoencapsulation with whey protein.
abstract: To improve bioavailability and enhance colon cancer prevention ability of curcumin, whey protein was used to nanoencapsulate at three different ratios such as 70:30, 50:50 and 35:65 for the first time. The drug loading, entrapment efficiency and structural changes of curcumin was confirmed by quantitative NMR spectroscopy. The nanoparticles prepared using the three ratios had an average diameters of 236.5±8.8, 212±3.4, and 187±11.4nm, as well as zeta (ζ) potentials of -13.1,-9.26, and -4.63mV, respectively, at pH 7.0. The cytotoxicity assay was performed for human colon and prostate cancer (SW480 and LNCap) by MTT assay and results showed significantly higher cytotoxicity of nanoencapsulated curcumin (NEC) (equivalent to 30.91, 20.70 and 16.86µM of NEC-1, 2 and 3 respectively), as compared to plain curcumin at 50µM after 72h of treatment. Cytotoxicity was also confirmed by microscopy of treated cells stained with acridine orange and propidium iodide. The cells treated with 50µM of curcumin, 30.91µM (NEC-1), 20.70µM (NEC-2) and 16.86µM (NEC-3) showed enhanced activation of p53 and elevated bax/Bcl2 expression (NEC-3), increased cytochrome-c in cytosol (NEC-2) confirming the enhanced cytotoxicity. To confirm the increased bioavailability, the intracellular curcumin was measured using fluorescence intensity. The fluorescent signal for intracellular curcumin was increased by 12, 30, and 21% for NEC-1, NEC-2, and NEC-3 respectively as compared to plain curcumin at 4h. Based on these results, we conclude that nanoencapsulated curcumin with whey protein will have potential to be considered for clinical applications for future studies.
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, United States. Electronic address: gkjp@tamu.edu.
authors.forename: Guddadarangavvanahally K
authors.initials: GK
authors.lastname: Jayaprakasha
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, United States; Central Research Laboratory, MS Ramaiah Medical College & Hospitals, MSR Nagar, MSRIT Post, Bangalore 560 054, India.
authors.forename: Kotamballi N
authors.initials: KN
authors.lastname: Chidambara Murthy
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77845-2119, United States. Electronic address: b-patil@tamu.edu.
authors.forename: Bhimanagouda S
authors.initials: BS
authors.lastname: Patil
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D000067816:Whey Proteins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D000067816:Whey Proteins; D003474:Curcumin
keywords: Colon cancer; Curcuma longa; Curcumin (PubChem CID 969516); Nanoencapsulation; Whey protein; Zeta potential