Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway

Abstract

The preliminary anti-cancer activity of Naringenin (Nar) has been proven in several cancers. However, the therapeutic activity of Nar on gastric cancer SGC-7901 cell line is not yet well understood. The aim of the present study was to investigate the effect and mechanisms of Nar on proliferation, apoptosis, migration, and invasion of SGC-7901 cells. In this in vitro study, SGC-7901 cells were treated with Nar at serial concentrations. Our data showed that Nar efficiently inhibited SGC-7901 cell proliferation in a time- and concentration-dependent manner, as well as downregulated proliferating cell nuclear antigen (PCNA) levels in a concentration-dependent manner. Meanwhile, the cell migration and invasion also dramatically decreased after Nar incubation, and the expressions of MMP2 and MMP9 were significantly downregulated. In addition, a strong proapoptotic effect was observed in the SGC-7901 cells after Nar treatment. Apoptosis-related proteins Bax and cleaved caspase-3 were up-regulated, whereas Bcl-2 and Survivin were downregulated. After administration with Nar, we found that phosphorylation of AKT was inhibited, and this inhibitory action could be mildly enhanced by the combination treatment of Nar and AKT inhibitor LY294002. In conclusion, our study confirmed that Nar could inhibit SGC-7901cell proliferation, migration, and invasion as well as induces apoptosis, and Nar might provide a new potential therapeutic strategy for treating gastric cancer.

Citrus fruit intake and gastric cancer: The stomach cancer pooling (StoP) project consortium

“…The mechanisms underneath this potential protective effect were investigated in studies based on gastric cancer cell lines and animal‐models. These showed anticancer effects of flavanones, a class of flavonoids contained almost exclusively in citrus fruits and juices . Hesperitin and naringenin, two of the major flavanones compounds contained in oranges and mandarins, inhibit human gastric cancer cell proliferation, migration and invasion in a dose‐ and time‐dependent manner .…”

“…These showed anticancer effects of flavanones, a class of flavonoids contained almost exclusively in citrus fruits and juices. [34][35][36][37][38] Hesperitin and naringenin, two of the major flavanones compounds contained in oranges and mandarins, inhibit human gastric cancer cell proliferation, migration and invasion in a dose-and time-dependent manner. 34,36 Moreover, naringenin showed a combinative effect on human gastric cell lines when administered in combination with ABT-737, an inhibitor of the antiapoptotic protein B-cell lymphoma.…”

“…[34][35][36][37][38] Hesperitin and naringenin, two of the major flavanones compounds contained in oranges and mandarins, inhibit human gastric cancer cell proliferation, migration and invasion in a dose-and time-dependent manner. 34,36 Moreover, naringenin showed a combinative effect on human gastric cell lines when administered in combination with ABT-737, an inhibitor of the antiapoptotic protein B-cell lymphoma. 37 These findings were confirmed in a study based on albino rats, in which the administration of naringenin simultaneously with and subsequently to the gastric carcinogen N-methyl-N 0 -nitroce-nitroso-guanidine reduced the tumor mass via its antioxidant potential.…”

Natural Polyphenols for Prevention and Treatment of Cancer

“…Besides, in SGC-7901 gastric cancer cells, naringenin treatment inhibited cancer cell proliferation, invasion, and migration and induced apoptosis, which might be related to its inhibition of the Akt signaling pathway [61]. Another study in colon cancer cells suggested that the pro-apoptotic activity of naringenin was mediated by the p38-dependent pathway [62].…”

Role of Flavonoids in DNA Damage and Carcinogenesis Prevention

“…Flavonoids, quercetin and rutin, protected Caco-2 cells against tert-butylhydroperoxide and menadione-induced DNA single strand breaks by their metal ion chelating ability [85]. Naringenin: Naringin is found in grapes and citrus fruit and and have shown promising results in the treatment of obesity, metabolic disorders [86] and its anti-cancer and chemo-sensitizing properties are also reported [87][88][89]. For instance, Naringenin inhibited azoxymethane induced colon carcinogenesis and lowered the number of high multiplicity aberrant foci [90].…”