TY - JOUR
T1 - Efficacy of PLGA-loaded apigenin nanoparticles in Benzo[a]pyrene and ultraviolet-B induced skin cancer of mice
T2 - Mitochondria mediated apoptotic signalling cascades
AU - Das, Sreemanti
AU - Das, Jayeeta
AU - Samadder, Asmita
AU - Paul, Avijit
AU - Khuda-Bukhsh, Anisur Rahman
N1 - Funding Information:
This work was partially supported by a grant sanctioned to Prof. A. R. Khuda-Bukhsh, Department of Zoology, University of Kalyani, Kalyani 741235, India by Boiron Laboratory, Lyon, France. We are also thankful to Dr. Kumaresh Ghosh, Mr. Debasish Kar, Mr. Debojyoti Tarafdar, Department of Chemistry, University of Kalyani, India, Dr. Tarak Das Basu, Ms. Ruchira Chakraborty, Department of Biochemistry, University of Kalyani, India. We are grateful to IACS for AFM and CD spectroscopy and Dr. T.C. Nag and Dr. Sandeep Arya, Department of Anatomy, AIIMS, India for TEM.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Apigenin
KW - Apoptosis
KW - Benzo[a]pyrene
KW - PLGA-nano-encapsulation
KW - Ultra-violet-B
UR - http://www.scopus.com/inward/record.url?scp=84886296886&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2013.09.037
DO - 10.1016/j.fct.2013.09.037
M3 - Article
C2 - 24120900
AN - SCOPUS:84886296886
SN - 0278-6915
VL - 62
SP - 670
EP - 680
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -
