Hesperidin loaded Zn2+@ SA/PCT nanocomposites inhibit the proliferation and induces the apoptosis in colon cancer cells (HCT116) through the enhancement of pro-apoptotic protein expressions

J Photochem Photobiol B. 2020 Mar:204:111767. doi: 10.1016/j.jphotobiol.2019.111767. Epub 2019 Dec 28.

Abstract

Colon carcinoma is a recurring type of cancer that affects the intestine epithelial with a poor survival rate. It was already proven the anticancer property of hesperidin in various cancers but the bioavailability hesperidin is poor, which hinders the hesperidin usage. In this investigation we synthesized hesperidin loaded Zn2+@ SA/PCT nanocomposites and assessed its anticancer potential against colon cancer (HCT116) cells. Hesperidin loaded Zn2+@ SA/PCT nanocomposites were characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis. The drug releasing capacity and cytotoxic property was assessed via drug releasing assay, MTT assay with HCT116 cells. The anticancer potency of hesperidin nanocomposites were evaluated with TUNEL, DAPI staining, reactive oxygen species (ROS) generation assay and it is confirmed with flow cytometry analysis of MMP disruption in colon cancer (HCT116) cell line. Further the immunoblotting analysis of cysteine proteases Caspases 3, 9, PARP, proapoptotic protein Bax and antiapoptotic protein Bcl2 were performed. The results of FTIR, XRD and electroscopic analyses confirmed the synthesized hesperidin nanocomposites accomplish the properties of potent nanodrug and the MTT assay authentically confirmed that the synthesized hesperidin nanocomposite inhibited the HCT116 cell growth, and the results of fluorescent staining proved that the hesperidin nanocomposite induced the apoptotic mediated cell necrosis via promoting the expression of apoptotic proteins thereby induced the apoptosis in colon cancer (HCT116) cells. Hence, it was concluded that the, hesperidin loaded nanocomposites persuasively inhibited proliferation of colon carcinoma cell and induced apoptosis in in vitro condition.

Keywords: Apoptosis; Caspase; Colon cancer; HCT116 cells; Hesperidin; MMP and anticancer drug; PARP; Zn(2+)@SA/PCT nanocomposites.

MeSH terms

  • Alginates / chemistry
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Drug Compounding
  • Drug Liberation
  • HCT116 Cells
  • Hesperidin / chemistry*
  • Hesperidin / pharmacology
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Nanocomposites / chemistry*
  • Pectins / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Zinc / chemistry

Substances

  • Alginates
  • Antineoplastic Agents, Phytogenic
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Pectins
  • Hesperidin
  • Caspase 3
  • Zinc