hydroxysafflor-yellow-a and Stomach-Neoplasms

BACKGROUND Anti-tumor properties of hydroxysafflor-yellow A (HSYA) have been recently revealed, as a series of apoptotic factors were confirmed to be regulated by HSYA and associated with peroxisome proliferator-activated receptor Gamma (PPARγ). In this study, we investigated the cell apoptosis mechanism of HSYA via activated PPARγ signal in human gastric carcinoma cells. MATERIAL AND METHODS BGC-823 cells were cultured and divided into 5 independent groups: Tumor, HSYA, HSYA+PPARγ inhibitor (GW9662), and PPARg agonist (RGZ), RGZ+GW9662. Cell proliferative activity was measured by MTT. Apoptosis and cell cycle were detected by flow cytometry. The nuclear translocation of PPARγ was detected by immunofluorescence staining chemistry, and mRNA levels of PPARγ and caspase-3 were measured by real-time qPCR. RESULTS Compared to the RGZ group, the HSYA group (100 µM) showed a similar inhibitory effect on the proliferation process of BGC-823 cells, inducing their apoptosis. As a result, the transition of BGC-823 cells from G0/G1 phase to S phase was blocked. HSYA was also found to promote the nuclear translocation of PPARγ, leading to increased expression of PPARγ and caspase-3. The regulatory effect of HSYA on BGC-823 cells could be further inhibited by PPARγ inhibitor in group GW9662. CONCLUSIONS We report the inhibitory effect of HSYA on the proliferation of BGC-823 cells, which results in activating PPARg-dependent cell cycle blocking and cell apoptosis, suggesting that PPARg is a specific type of HSYA that can induce apoptosis of BGC-823 cells.

Topics: Apoptosis; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Chalcone; Gene Expression Regulation, Neoplastic; Humans; Neovascularization, Pathologic; PPAR gamma; Protein Transport; Quinones; RNA, Messenger; Staining and Labeling; Stomach Neoplasms

To study the effects of hydroxy safflower yellow A (HSYA) on tumor capillary angiogenesis in transplanted human gastric adenocarcinoma BGC-823 tumors in nude mice.. BGC-823 cells were injected subcutaneously into the right anterior armpit of nude mice to establish an animal model of transplanted tumors. After 24 h, 18 nude mice injected with tumor cells were randomized into model, control, and HSYA 0.028 g/L groups, with six mice in each group. Transplanted tumors were excised on day 20. Tumor inhibition ratios were calculated for the transplanted tumors. Pathological changes and capillary angiogenesis in the tumors were observed by light microscopy.. Tumors in the model group grew more quickly than those in the control and HSYA groups, with inhibition ratios of 48% and 30%, respectively. The microvessel count in the HSYA group was lower than in the model group (P < 0.01), and microvessel density was also lower in the HSYA group (P < 0.05). Pathological changes were more obvious in tumors in the model group compared to the HSYA group.. HSYA inhibits the growth of transplanted BGC-823 tumors, and its effects on tumor capillary angiogenesis may represent one of the mechanisms responsible for this antineoplastic effect.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Capillaries; Chalcone; Female; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Quinones; Stomach Neoplasms; Xenograft Model Antitumor Assays

To investigate the effects of Hydroxy Safflor yellow A (HSYA) on the growth of blood vessel of transplantation tumor of gastric adenocarcinoma cell line BGC-823 in nude mice and its underlying mechanism of antagonizing tumor angiogenesis.. The BGC-823 cells was subcutaneouly injected into the right anterior armpit of BALB/C nu/nu nude mice and established the animal model of transplantation tumor. Then nude mice were divided into 4 groups at random: model group, control group, high or low dosage of HSYA group. The model group were treated with normal sodium by intraperitoneal injection, HSYA groups were treated with HSYA at concentration of 0.056 g x L(-1) and 0.028 g x L(-1) by intraperitoneal injection, and in these groups each mouse was injected 2 times everyday with 0.2 mL by 4-6 hours interval. The control group were injected in enterocoelia 1 times every 2 days starting from the third day with cytoxan at 2 g x L(-1). 20 days later, the volume and weight of nude mice were observed. The pathological change of tumor tissue was observed under optical microscope. The mRNA expression of VEGF and bFGF of transplantation tumor were detected by real time quantitative PCR.. The volume (607.42 +/- 252.96) mm3, weight (0.88 +/- 0.14) g of transplantation tumor, the mRNA expression level of VEGF 0.49 +/- 0.13 and bFGF 0.60 +/- 0.48 are reduced significantly after treatment with HSYA at the concentration of 0.028 g x L(-1) compared with physiologic saline-treated group (P < 0.05 or P < 0.01). The tumor pathological angiogenesis of HSYA group is also less obvious than the normal sodium-treated group.. HSYA in given concentration can inhibit the growth of BGC-823 transplantation tumor, and decreasing the mRNA expression of VEGF and bFGF, which suggests that inhibiting tumor angiogenesis may be one of the mechanisms of HSYA antagonizing tumor.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Animals; Blood Vessels; Cell Line, Tumor; Chalcone; Drugs, Chinese Herbal; Female; Fibroblast Growth Factors; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Quinones; Random Allocation; Stomach Neoplasms; Vascular Endothelial Growth Factor A