title: Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer.
abstract: Prostate cancer is the most commonly diagnosed cancer disease in men in the Unites States and its management remains a challenge in everyday oncology practice. Thus, advanced therapeutic strategies are required to treat prostate cancer patients. Curcumin (CUR) is a promising anticancer agent for various cancer types. The objective of this study was to evaluate therapeutic potential of novel poly(lactic-co-glycolic acid)- CUR nanoparticles (PLGA-CUR NPs) for prostate cancer treatment. Our results indicate that PLGA-CUR NPs efficiently internalize in prostate cancer cells and release biologically active CUR in cytosolic compartment of cells for effective therapeutic activity. Cell proliferation (MTS), clonogenic, and Western blot analyses reveal that PLGA-CUR NPs can effectively inhibit proliferation and colony formation ability of prostate cancer cells than free CUR. PLGA-CUR NPs showed superior tumor regression compared to CUR in xenograft mice. Further investigations reveal that PLGA-CUR NPs inhibit nuclear β-catenin and AR expression in cells and in tumor xenograft tissues. It also suppresses STAT3 and AKT phosphorylation and leads to apoptosis via inhibition of key anti-apoptotic proteins, Mcl-1, Bcl-xL and caused induction of PARP cleavage. Additionally, significant downregulation of oncogenic miR21 and up-regulation of miR-205 was observed with PLGA-CUR NPs treatment as determined by RT-PCR and in situ hybridization analyses. A superior anti-cancer potential was attained with PSMA antibody conjugated PLGA-CUR NPs in prostate cancer cells and a significant tumor targeting of (131)I labeled PSMA antibody was achieved with PLGA-CUR NPs in prostate cancer xenograft mice model. In conclusion, PLGA-CUR NPs can significantly accumulate and exhibit superior anticancer activity in prostate cancer.
authors.affiliation: Department of Pharmaceutical Sciences and The Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Yallapu
authors.affiliation: Department of Pharmaceutical Sciences and The Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Sheema
authors.initials: S
authors.lastname: Khan
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Maher
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Mara C
authors.initials: MC
authors.lastname: Ebeling
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sundram
authors.affiliation: Department of Pharmaceutical Sciences and The Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Chauhan
authors.affiliation: Department of Pharmaceutical Sciences and The Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Ganju
authors.affiliation: Department of Pharmaceutical Sciences and The Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Swathi
authors.initials: S
authors.lastname: Balakrishna
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, SD 57104, USA.
authors.forename: Brij K
authors.initials: BK
authors.lastname: Gupta
authors.affiliation: Department of Pathology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Zafar
authors.affiliation: Department of Pharmaceutical Sciences and The Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.affiliation: Department of Pharmaceutical Sciences and The Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: schauha1@uthsc.edu.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D011944:Receptors, Androgen; D051176:beta Catenin; D017430:Prostate-Specific Antigen; D003474:Curcumin
keywords: Chemoprevention; Curcumin; Nanoparticles; Prostate cancer; Targeted delivery