Title:Combination of ZnO Nanoparticle with Marine Sponge Derived Dipeptide for Enhanced Anticancer Efficacy in Liver Cancer Cells and their Toxicity Evaluation on Embryonic Zebrafish
Volume: 17
Issue: 5
Author(s): Gayathri Karanam, Arumugam Madan Kumar*, Chinmai Sriamulya Yerukalapudi, Nagabhishek Sirpu Natesh, Rajender Boddula and Ramyakrishna Pothu
Affiliation:
- Cancer Biology Lab, Molecular and Nanomedicine Research Unit, Sathyabama Institute of Science and Technology (Deemed to be University), Chennai-600119. Tamil Nadu,India
Keywords:
Anticancer, apoptosis, dipeptide, marine sponge, zebrafish embryotoxicity, ZnO nanoparticles.
Abstract:
Background: Nanomaterials-based cancer therapy plays a significant role in increasing
the therapeutic efficiency of anticancer drugs, reducing side effects and targeted delivery of the drug
payloads. The present study was aimed to enhance the anticancer effect of a novel dipeptide isolated
from marine sponge-associated Bacillus pumilus AMK1 by formulating with Zinc oxide (ZnO) nanoparticles
for the effective treatment against HepG2 liver cancer cells.
Methods: ZnO nanoparticles were synthesized by chemical method and size of the nanoparticle was
characterized by Scanning electron microscope, X-Ray diffraction and Fourier-transform infrared
spectroscopy. Furthermore, ZnO nanoparticles were conjugated with the isolated dipeptide and evaluated
for anticancer activity. In addition, distinct morphological changes were observed by performing
apoptotic staining methods such as propidium iodide staining and acridine orange/ ethidium bromide
staining. Furthermore, embryotoxic and teratogenic effects of conjugated dipeptide on the development
of zebrafish embryo were investigated in this study.
Results: It was observed that conjugated dipeptide showed enhanced cytotoxicity against HepG2 liver
cancer cells without any toxic effect on normal liver cells. ZnO with dipeptide showed significant
higher apoptosis of liver cancer cells, with around 19% in early apoptosis and 53% in late apoptosis
stage. The obtained results suggest that ZnO nanoparticle conjugated dipeptide initiated cytotoxicity
through apoptotic death in HepG2 cells. The embryotoxic studies in zebrafish embryos revealed the
LC50 197.0 μg/mL. These findings suggest that conjugated dipeptide affected the development of
zebrafish embryos only at relatively higher concentrations.
Conclusion: The experimental results demonstrate that ZnO nanoparticle conjugated dipeptide has
the potential to improve anticancer efficacy against liver cancer cells by inducing apoptosis in cancer
cells without any effect on normal liver cells.