title: Curcumin Nanoformulation for Cervical Cancer Treatment.
abstract: Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear β-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer.
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Mohd S
authors.initials: MS
authors.lastname: Zaman
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Chauhan
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Yallapu
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Rishi K
authors.initials: RK
authors.lastname: Gara
authors.affiliation: Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, 57104, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Maher
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Sonam
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sikander
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Sheema
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Pathology, University of Tennessee at Memphis, Memphis, TN, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Zafar
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.affiliation: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA.|Department of Pathology, University of Tennessee at Memphis, Memphis, TN, USA.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003474:Curcumin
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