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

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

Review of factors affecting citrus polyphenol bioavailability and their importance in designing in vitro, animal, and intervention studies

“…Firstly, studies should focus on using physiologically relevant forms of compounds and doses in the appropriate cell/enzyme models. It is not relevant to apply citrus extracts (Buachan et al., 2014; Kim & Kim, 2016; Su et al., 2019) or flavanone glycosides (Claussnitzer et al., 2011; Parmar et al., 2012; Shen et al., 2012) directly to non‐gut cells since cells within the body will not encounter the parent glycosides, as discussed above. The citrus flavanones (hesperidin 3 , narirutin 4 , and naringin 7 ) are mainly metabolized in the colon, and the released aglycones are then either absorbed and conjugated by the phase II enzymes in the enterocytes and/or liver, or are further metabolized by the gut microbiota to yield the phenolic catabolites (Brett et al., 2009; Pereira‐Caro et al., 2016).…”