gingerol and Stomach-Neoplasms

Gastric cancer is the world's fifth most prevalent cancer and its treatments are associated with issues. In this investigation, a UIO-66 nanoparticle was loaded with Gingerol (UIO-66-Gin) as a great drug carrier vehicle for chemotherapy of the AGS cancer cell lines.. UIO-66-Gin characterization was performed using SEM, DLS and FTIR tests. The release profile of Gin from UIO-66 was also assessed. The cytotoxicity of UIO-66-Gin against AGS cells was assessed using MTT assay. Caspase3, Caspase9, Bax, and Bcl2 genes expression was evaluated via Real-time PCR and apoptosis rate was performed using flow-cytometry assay. Size analysis indicated the spherical shape of nano-formulation with the mean size of 174.3 nm. Release analysis indicated that there was a 50% Gin release from the nanocarrier was reported in roughly 21 h, which revealed the regulated release of bioactive compound from the UIO-66 formulation in PBS medium. After 48 and 72 h, various concentration of both the Gin and UIO-66-Gin started to induce cytotoxicity in cancerous cells. However, the induction of cytotoxicity was higher in cells treated with UIO-66-Gin. UIO-66-Gin could induce the expression of pro-apoptotic (Bax, Caspase3, and Caspase9) genes and down-regulate the expression of Bcl2 as anti-apoptotic gene rather than other formulation. Flowcytometry results indicated that the elevation of apoptotic rate in cells treated with UIO-66-Gin was significantly higher than Gin treated cells.. Our investigation revealed the potent anticancer effect and apoptotic induction ability of UIO-66-Gin against cancerous cells through altering the expression of genes involved in apoptosis.

Topics: Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Humans; Nanoparticles; Organometallic Compounds; Proto-Oncogene Proteins c-bcl-2; Stomach Neoplasms

Cisplatin-based chemotherapy is a widely used chemotherapeutic regimen for gastric cancer; however, drug resistance limits its efficacy. [6]-Gingerol has been found to exhibit anticancer effects. Here, we aim to explore the potential of [6]-gingerol in combination with cisplatin as a new regimen for gastric cancer. CCK-8 assay and colony formation assay were used to determine the effect of [6]-gingerol in combination with cisplatin on cell viability of gastric cancer cells. Flow cytometry was performed to assess cell cycle distribution. Wound-healing assay and transwell invasion assay were conducted to examine the migration and invasion abilities. Cell cycle and invasion-related proteins and mRNAs, as well as PI3K/AKT signaling proteins, were assessed by western blotting and quantitative real-time polymerase chain reaction. Combination of [6]-gingerol with cisplatin inhibited cell viability and enhanced cell cycle arrest at G1 phase compared with cisplatin alone. The combination treatment inhibited cell migration and invasion ability and decreased cyclin D1, cyclin A2, matrix metalloproteinase-9, p-PI3K, AKT, and p-AKT protein expressions and increased P21 and P27 mRNA levels. Our study demonstrates that [6]-gingerol enhances the cisplatin sensitivity of gastric cancer cells and that the mechanisms involve G1 phase arrest, migration and invasion suppression via PI3K/AKT signaling pathway.

Topics: Catechols; Cell Proliferation; Cisplatin; Fatty Alcohols; Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Stomach Neoplasms

Ionizing radiation (IR) is the main modality for locoregional control of unresectable gastric cancer (GC). [6]-Gingerol is an active major phenolic compound isolated from ginger (Zingiber officinale Roscoe), and it has been demonstrated to possess antitumor activity in previous studies. In the present study, we aimed to evaluate the potential activity of [6]-gingerol as a radiosensitizer and to further explore the underlying mechanism. A CCK-8 assay revealed that [6]-gingerol inhibited the cell viability of HGC-27 cells in a dose-dependent manner (P<0.05). Colony formation assay indicated that pretreatment of [6]-gingerol prior to IR decreased the clonogenic survival of HGC-27 cells. Notably, the combination of [6]-gingerol with IR enhanced IR-induced cell cycle arrest at the G2/M phase compared with IR alone (41.3% in IR alone vs. 53.5% in [6]-gingerol+IR; P=0.006), and increased IR-induced apoptosis compared with IR alone (9.6% in IR alone group vs. 15.1% in [6]-gingerol+IR; P=0.07). DAPI staining detected the apoptotic nuclear morphological changes in the cells treated with [6]-gingerol and/or IR. Furthermore, western blotting and qRT-PCR revealed that [6]-gingerol pretreatment following IR downregulated the protein expression of cyclin B1, cyclin A2, CDC2 and cyclin D1, upregulated the mRNA expression of p27, and induced active caspase-9, active caspase-3 and cytochrome c. In conclusion, the present study demonstrated that [6]-gingerol enhanced radiosensitivity of GC cells, and that the mechanisms involved at least G2/M phase arrest and apoptosis induction.

Topics: Caspases; Catechols; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemoradiotherapy; Cytochromes c; Dose-Response Relationship, Drug; Fatty Alcohols; Gene Expression Regulation, Neoplastic; Humans; Radiation-Sensitizing Agents; Stomach Neoplasms

Ginger (Zingiber officinale Roscoe), a monocotyledonous herb, is widely used as an herbal medicine owing to the phytoconstituents it possesses. In the current study, the quantity of [6]-gingerol, the major phenolic ketone, in the fresh ginger and dried ginger rhizome was found to be 6.11 µg/mg and 0.407 µg/mg. Furthermore, [6]-gingerol was assessed for its antiapoptotic effects in human gastric adenocarcinoma (AGS) cells evidenced by acridine orange/ethidium bromide staining technique and Annexin-V assay. An increase in reactive oxygen species (ROS) generation led to a decrease in mitochondrial membrane potential (MMP) and subsequent induction of apoptosis. Results disclose that perturbations in MMP are associated with deregulation of Bax/Bcl-2 ratio at protein level, which leads to upregulation of cytochrome-c triggering the caspase cascade. These enduringly suggest that [6]-gingerol can be effectively used for targeting the mitochondrial energy metabolism to manage gastric cancer cells.

Topics: Acridine Orange; Adenocarcinoma; Annexin A5; Apoptosis; bcl-2-Associated X Protein; Caspases; Catechols; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromatography, High Pressure Liquid; Cytochromes c; Ethidium; Fatty Alcohols; Humans; Membrane Potential, Mitochondrial; Plant Extracts; Protein Binding; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Stomach Neoplasms; Up-Regulation; Zingiber officinale

Ginger has been used throughout the world as spice, food and traditional herb. We found that 6-gingerol, a phenolic alkanone isolated from ginger, enhanced the TRAIL-induced viability reduction of gastric cancer cells while 6-gingerol alone affected viability only slightly. 6-Gingerol facilitated TRAIL-induced apoptosis by increasing TRAIL-induced caspase-3/7 activation. 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL-induced NF-kappaB activation. As 6-shogaol has a chemical structure similar to 6-gingerol, we also assessed the effect of 6-shogaol on the viability of gastric cancer cells. Unlike 6-gingerol, 6-shogaol alone reduced the viability of gastric cancer cells. 6-Shogaol was shown to damage microtubules and induce mitotic arrest. These findings indicate for the first time that in gastric cancer cells, 6-gingerol enhances TRAIL-induced viability reduction by inhibiting TRAIL-induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules.

Topics: Animals; Caspase 3; Caspase 7; Catechols; Cell Line, Tumor; Cell Survival; Fatty Alcohols; Humans; Mice; Mice, Nude; Microtubules; NF-kappa B; Plant Extracts; Stomach Neoplasms; TNF-Related Apoptosis-Inducing Ligand; Zingiber officinale