Hydroxysafflor-Yellow A Induces Human Gastric Carcinoma BGC-823 Cell Apoptosis by Activating Peroxisome Proliferator-Activated Receptor Gamma (PPARγ)

Abstract

BackgroundAnti-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/MethodsBGC-823 cells were cultured and divided into 5 independent groups: Tumor, HSYA, HSYA+PPARγ inhibitor (GW9662), and PPARγ 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.ResultsCompared 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.ConclusionsWe report the inhibitory effect of HSYA on the proliferation of BGC-823 cells, which results in activating PPARγ-dependent cell cycle blocking and cell apoptosis, suggesting that PPARγ is a specific type of HSYA that can induce apoptosis of BGC-823 cells.

Hydroxysafflor yellow A inhibited lipopolysaccharide‐induced non‐small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

“…Previous studies have reported that HYSA induces human gastric carcinoma BGC-823 cell apoptosis by activating PPARγ and suppresses angiogenesis in transplanted human gastric adenocarcinoma BGC-823 tumors in nude mice. 27,28 HYSA inhibits the angiogenesis of hepatocellular carcinoma by blocking ERK/MAPK and NF-κB signaling pathways in H22 tumor-bearing mice and suppresses the adhesion, invasion, migration, and lung metastasis of hepatoma cells. 29,30 However, the role and underlying mechanisms of HYSA in LPS-induced A549 and H1299 cells remains unknown.…”

“…Previous studies have shown that HSYA promotes blood circulation for removing blood stasis and positively affects antioxidant, anti‐inflammatory, and antitumor activities . Furthermore, HSYA can induce human gastric carcinoma BGC‐823 cell apoptosis by activating peroxisome proliferator‐activated receptor gamma (PPARγ), and suppress tumor capillary angiogenesis in transplanted human gastric adenocarcinoma BGC‐823 tumors in nude mice . HSYA can also suppress adhesion, invasion, migration, and lung metastasis of hepatoma cells via the E‐cadherin/β‐catenin pathway, and inhibit angiogenesis of hepatocellular carcinoma by blocking the ERK/MAPK and NF‐κB signaling pathways in H22 tumor‐bearing mice .…”

Antioxidant and Pro-Oxidant Properties of Carthamus Tinctorius, Hydroxy Safflor Yellow A, and Safflor Yellow A

“…Among molecular mechanisms, antioxidant activity has been described [7,11]. Moreover, HSYA significantly inhibits abnormal proliferation of tumor cell in the culture, without affecting normal endothelial cell growth [12]. HSYA reduces also apoptosis in pancreatic β-cells by attenuating oxidative damage and JNK/c-Jun signaling pathway [13].…”

Hydroxysafflor yellow�A induces autophagy in human liver cancer cells by regulating Beclin�1 and ERK expression

“…Due to its potency and minimal side effects, the clinical use of HSYA has continued to increase since 2000 (7). Previous studies have reported that safflower exerts antitumor effects (8), and it has been reported that HSYA prevented pulmonary metastasis in liver cancer cells (9), induced apoptosis in human gastric carcinoma cells (BGC-823 cells) (10) and inhibited the growth of transplanted BGC-823 tumors. Another study also reported that the effect of HSYA on tumor capillary angiogenesis may be one of the mechanisms underlying its antineoplastic effect (11).…”