Eugenol-piperine loaded polyhydroxy butyrate/polyethylene glycol nanocomposite-induced apoptosis and cell death in nasopharyngeal cancer (C666-1) cells through the inhibition of the PI3K/AKT/mTOR signaling pathway

J Biochem Mol Toxicol. 2021 Apr;35(4):e22700. doi: 10.1002/jbt.22700. Epub 2021 Jan 9.

Abstract

Nasopharyngeal cancer is a malignancy developing from the nasopharynx epithelium due to smoking and nitrosamine-containing foods. Nasopharyngeal cancer is highly endemic to Southeast Asia. Eugenol and piperine have shown many anticancer activities on numerous cancer types, like colon, lung, liver, and breast cancer. In this study, we amalgamated eugenol and piperine loaded with a polyhydroxy butyrate/polyethylene glycol nanocomposite (Eu-Pi/PHB-PEG-NC) for better anticancer results against nasopharyngeal cancer (C666-1) cells. In the current study, nasopharyngeal cancer cell lines C666-1 were utilized to appraise the cytotoxic potential of Eug-Pip-PEG-NC on cell propagation, programmed cell death, and relocation. Eu-Pi/PHB-PEG-NC inhibits cellular proliferation on C666-1 cells in a dose-dependent manner, and when compared with 20 µg/ml, 15 µg/ml of loaded mixture evidently restrained the passage aptitude of C666-1 cells, this was attended with a downregulated expression of mitochondrial membrane potential. Treatment with 15 µg/ml Eu-Pi/PHB-PEG-NC suggestively amplified cell apoptosis in the C666-1 cells. Furthermore, its cleaved caspase-3, 8, and 9 and Bax gene expression was augmented and Bcl-2 gene expression was diminished after Eu-Pi/PHB-PEG-NC treatment. Additionally, our data established that the collective effect of Eu-Pi/PHB-PEG-NC loaded micelles inhibited the expansion of C666-1 cells augmented apoptosis connected with the intrusion of PI3K/Akt/mTOR signaling pathway.

Keywords: C666-1 cells; apoptosis; eugenol; nasopharyngeal cancer; piperine; polyhydroxy butyrate.

MeSH terms

  • Alkaloids* / chemistry
  • Alkaloids* / pharmacology
  • Apoptosis / drug effects*
  • Benzodioxoles* / chemistry
  • Benzodioxoles* / pharmacology
  • Cell Line, Tumor
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacology
  • Elafin / metabolism
  • Eugenol* / chemistry
  • Eugenol* / pharmacology
  • Humans
  • Nanocomposites* / chemistry
  • Nanocomposites* / therapeutic use
  • Nasopharyngeal Neoplasms* / drug therapy
  • Nasopharyngeal Neoplasms* / metabolism
  • Nasopharyngeal Neoplasms* / pathology
  • Piperidines* / chemistry
  • Piperidines* / pharmacology
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology
  • Polyhydroxyalkanoates / chemistry
  • Polyhydroxyalkanoates / pharmacology
  • Polyunsaturated Alkamides* / chemistry
  • Polyunsaturated Alkamides* / pharmacology
  • Prohibitins
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Alkaloids
  • Benzodioxoles
  • Drug Carriers
  • Elafin
  • PHB protein, human
  • PI3 protein, human
  • Piperidines
  • Polyhydroxyalkanoates
  • Polyunsaturated Alkamides
  • Prohibitins
  • Eugenol
  • Polyethylene Glycols
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • piperine