xanthohumol and Stomach-Neoplasms

We assessed the effect of xanthohumol (XN) on gastric cancer (GC) in vitro and in vivo. XN reduced the viability of SGC-7901, SNU216, and SNU668 cells, but not GES-1 non-tumorigenic human gastric epithelial cells. XN induced apoptosis in SGC-7901 cells in a concentration-dependent manner by enhancing the numbers of late and early apoptotic cells. XN also downregulated the anti-apoptotic proteins Bcl-XL and Bcl-2 and upregulated the pro-apoptotic proteins Bax, Bid, PARP, and caspase-3. XN induced phosphorylation of PI3K, Akt, and mTOR in SGC7901 cells. Also, XN reduced the tumour volume and weight by inhibiting the phosphorylation of Akt and mTOR. XN-treated tumours had significantly fewer proliferating cells and more apoptotic cells compared with the control. Our data indicate that XN induces apoptosis of human GC cells in vivo. Thus, XN may have potential as an anti-GC agent.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Enzyme Activation; Female; Flavonoids; Humans; Mice, Inbred BALB C; Mice, Nude; Phosphatidylinositol 3-Kinase; Phosphorylation; Propiophenones; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Stomach Neoplasms; Time Factors; TOR Serine-Threonine Kinases; Tumor Burden; Xenograft Model Antitumor Assays

Xanthohumol (Xn), a prenylated flavonoid isolated from Hops (Humulus lupulus L.), has demonstrated potent anticancer activity in multiple types of cancer. However, the effect of Xn on gastric cancer (GC) remains unknown. The aim of the present study was to investigate the effect of Xn on GC cell proliferation, apoptosis and metastasis. It was observed that Xn decreased the viability of GC cells, with very low or no toxicity to normal gastric epithelial cells GES‑1 at a concentration of 1‑100 µM. The proliferation of AGS cells was inhibited by Xn, as indicated by the decreased number of EdU‑positive cells. Xn treatment increased the number of apoptotic cells, downregulated the expression of Bcl‑2 and upregulated the expression of Bax, suggesting induction of apoptosis. The results from the wound healing and Transwell assays indicated that Xn suppressed AGS cell metastasis. Moreover, Xn induced reactive oxygen species (ROS) overproduction and inhibited nuclear factor (NF)‑κB signaling in AGS cells, which was reversed by the ROS inhibitor N‑acetylcysteine (NAC). NAC suppressed the effect of Xn on the proliferation, apoptosis and metastasis of AGS cells. Taken together, these results suggest that Xn exerts anticancer effects against GC via induction of ROS production and subsequent inhibition of NF‑κB signaling. Therefore, Xn may be a promising candidate treatment against GC progression.

Topics: Antineoplastic Agents; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Cell Survival; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; Propiophenones; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Signal Transduction; Stomach Neoplasms