Efficacy of PLGA-loaded apigenin nanoparticles in Benzo[a]pyrene and ultraviolet-B induced skin cancer of mice: mitochondria mediated apoptotic signalling cascades.

Abstract

Skin cancer is increasing at an alarming rate and becoming resistant to conventional chemotherapy necessitating improved drug delivery system. We loaded apigenin (Ap), a dietary flavonoid having anti-cancer property, with poly (lactic-co-glycolide) (PLGA) nanoparticles (NAp) to explore if nano-encapsulation could enhance anti-carcinogenic effect against ultra-violet B (UVB) and Benzo(a)pyrene (BaP) induced skin tumor and mitochondrial dysfunction in mice. Particle size, morphology and zeta potential of NAp were determined using dynamic light scattering and atomic force microscopy. Tumor incidence and multiplicity in UVB-BaP induced mice with/without NAp treatment were ascertained and their histolopathological sections and chromosomal aberrations were studied. ROS accumulation and mitochondrial functioning through relevant markers like mitochondrial transmembrane potential were analyzed. Mitochondrial volume changes/swelling, cytochrome c (cyt c) release, mRNA and protein expressions of Apaf-1, bax, bcl-2, cyt c, cleaved caspase-9 and 3 were studied. Results showed that NAp produced better effects than Ap, due to their smaller size, and faster mobility. NAp reduced tissue damage and frequency of chromosomal aberrations, increased ROS accumulation to mediate mitochondrial-apoptosis through modulation of several apoptotic markers and mitochondrial matrix swelling. NAp showed ameliorative potentials in combating skin cancer and therefore has greater prospect of use in therapeutic management of skin cancer.

• Authors: Sreemanti Das, Jayeeta Das, Asmita Samadder, Avijit Paul, Anisur Rahman Khuda-Bukhsh
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 62 Pg. 670-80 (Dec 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 24120900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anticarcinogenic Agents
• Drug Carriers
• Reactive Oxygen Species
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Benzo(a)pyrene
• Apigenin

Topics

• Animals
• Anticarcinogenic Agents (administration & dosage, pharmacology)
• Apigenin (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Benzo(a)pyrene (toxicity)
• Drug Carriers
• Lactic Acid (administration & dosage)
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mitochondria (drug effects, metabolism)
• Nanoparticles (administration & dosage, chemistry)
• Neoplasms, Radiation-Induced (drug therapy, metabolism)
• Polyglycolic Acid (administration & dosage)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Skin Neoplasms (chemically induced, drug therapy, metabolism)
• Ultraviolet Rays