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Co-Delivery of Curcumin and Chrysin by Polymeric Nanoparticles Inhibit Synergistically Growth and hTERT Gene Expression in Human Colorectal Cancer Cells.

Abstract
Nanoparticle (NP)-based combinational chemotherapy has been proposed as a potent approach for improving intracellular drug concentrations and attaining synergistic effects in colorectal cancer therapy. Here, two well-known herbal substances, Curcumin (Cur) and Chrysin (Chr), were co-encapsulated in PEGylated PLGA NPs and investigated their synergistic inhibitory effect against Caco-2 cancer cells. Characterization of nanoformulated drugs was determined using DLS, FTIR, TEM, and SEM. Drug release study was performed using dialysis method. MTT and real-time PCR assays were applied to evaluate the cytotoxic effects of free and nano-encapsulated drugs on expression level of hTERT in Caco-2 cells. The results showed that free drugs and nano-formulations exhibited a dose-dependent cytotoxicity against Caco-2 cells and especially, Cur-Chr-PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (P < 0.05). Real-time PCR results revealed that Cur, Chr, and combination of Cur-Chr in free and encapsulated forms inhibited hTERT gene expression. Also, it was found that Cur-Chr-PLGA/PEG NPs than free combination forms could further decline hTERT expression in all concentration (P < 0.05). In summary, our study represents the first report of nano-combinational application of the natural herbal substances with a one-step fabricated codelivery system for effective colorectal cancer combinational chemotherapy.
AuthorsJavid Lotfi-Attari, Younes Pilehvar-Soltanahmadi, Mehdi Dadashpour, Shahriar Alipour, Raana Farajzadeh, Shahrzad Javidfar, Nosratollah Zarghami
JournalNutrition and cancer (Nutr Cancer) 2017 Nov-Dec Vol. 69 Issue 8 Pg. 1290-1299 ISSN: 1532-7914 [Electronic] United States
PMID29083232 (Publication Type: Journal Article)
Chemical References
  • Flavonoids
  • Polyesters
  • polyethylene glycol-poly(lactide-co-glycolide)
  • chrysin
  • Polyethylene Glycols
  • TERT protein, human
  • Telomerase
  • Curcumin
Topics
  • Caco-2 Cells
  • Colorectal Neoplasms (drug therapy)
  • Curcumin (pharmacology)
  • Drug Delivery Systems
  • Drug Liberation
  • Drug Synergism
  • Flavonoids (pharmacology)
  • Humans
  • Nanoparticles (chemistry)
  • Particle Size
  • Polyesters (chemistry)
  • Polyethylene Glycols (chemistry)
  • Telomerase (genetics, metabolism)

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