Nano-encapsulated chlorophyllin significantly delays progression of lung cancer both in in vitro and in vivo models through activation of mitochondrial signaling cascades and drug-DNA interaction

Environ Toxicol Pharmacol. 2016 Sep:46:147-157. doi: 10.1016/j.etap.2016.07.006. Epub 2016 Jul 18.

Abstract

Chlorophyllin (CHL), a sodium-copper-salt derived from chlorophyll, has been widely used as a food-dye, also reportedly having some anti-cancer effect. We tested if PLGA-loaded CHL (NCHL) could have additional protective abilities through its faster and targeted drug delivery in cancer cells. Physico-chemical characterization of NCHL was done through atomic-force microscopy and UV-spectroscopy. NCHL demonstrated greater ability of drug uptake and strong anti-cancer potentials in non-small cell lung cancer cells, A549, as revealed from data of% cell viability, generation of reactive-oxygen-species and expression of bax, bcl2, caspase3, p53 and cytochrome c proteins. Circular dichroic spectral data indicated strong binding of NCHL with calf-thymus-DNA, causing a conformational/structural change in DNA. Further, NCHL could cross the blood-brain-barrier in mice and showed greater efficacy in recovery process of tissue damage, reduction in chromosomal aberrations and% of micronuclei in co-mutagens (Sodiumarsenite+Benzo[a]Pyrene)-treated mice at a much reduced dose, indicating its use in therapeutic oncology.

Keywords: A549 cells; Anti-cancer efficacy; Chlorophyllin; Mice; Mitochondrial signaling; Poly (lactic-co-glycolic) acid.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / pharmacology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Chlorophyllides / chemistry
  • Chlorophyllides / metabolism
  • Chlorophyllides / pharmacology*
  • Chromosome Aberrations
  • Circular Dichroism
  • Cytochromes c / metabolism
  • DNA / metabolism
  • Humans
  • Lactic Acid / chemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice, Inbred BALB C
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Chlorophyllides
  • Reactive Oxygen Species
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Cytochromes c
  • DNA
  • calf thymus DNA
  • chlorophyllin