Apoptotic properties of Citrus sudachi Hort, ex Shirai (Rutaceae) extract on human A549 and HepG2 cancer cells

  • Ji Hye Kim
  • Min Young Kim
Keywords: Apoptosis, Citrus sudachi, Human lung and liver cancer cells, Inhibitors of apoptosis, Nitric oxide

Abstract

Purpose: To investigate whether Citrus sudachi harvested at two stages of maturity can induce toxicity in a cell-specific manner and to determine the possible  mechanisms of Citrus sudachi-induced cytotoxic responses in two types of cancer cells (human lung adenocarcinoma A549 and hepatocellular carcinoma HepG2 cells) and two normal cell lines (lung 16HBE140- and liver CHANG cells).
Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodidle assay were used to test the antiproliferative activity and apoptosis of methanol extract of Citrus sudachi, respectively. Griess reaction and reverse transcriptase-polymerase chain reaction (RT-PCR) were carried out to evaluate nitric oxide (NO•) production and the mRNA levels of inhibitors of apoptosis (IAP).
Results: Citrus sudachi exerted cytotoxicity in a time-dependent manner in cancer cells which increased with increase in maturity but did not affect normal cells. Citrus sudachi was found to induce accumulation of cells in the sub-G1 cell cycle phase, fragmentation of DNA and cell death with characteristics of apoptosis, in both types of cancer cells. Moreover, Citrus sudachi upregulated cellular NO• produced by activation of nitric oxide synthase (NOS), while it suppressed the levels of IAP mRNA in both types of cancer cells.
Conclusion: The results obtained suggest that Citrus sudachi induces apoptosis in A549 and HepG2 cells, which may be mediated by NO•. There is need for further studies on the role of Citrus sudachi in cancer treatment.


Keywords: Apoptosis, Citrus sudachi, Human lung and liver cancer cells, Inhibitors of apoptosis, Nitric oxide

Published
2016-07-11
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996