Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway

Abstract

Abstract. The present study was designed to investigate the antiproliferative activity of isoimperatorin against SGC-7901 cells and to examine the possible mechanisms. The antiproliferative activity of isoimperatorin against SGC-7901 cells was evaluated using an MTT assay, and the mechanisms were investigated using flow cytometry and western blot assays, which were used to determine the apoptotic rate and expression levels of mitochondria-mediated apoptosis-associated proteins, including Survivin, myeloid leukemia cell-1 (Mcl-1), B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 (Bcl-2), second mitochondria-derived activator of caspase (Smac), Bcl-2-associated X factor (Bax), cleaved (c)-caspase-3 and c-caspase-9 in SGC-7901 cells. Additionally, a xenograft assay was used to confirm whether isoimperatorin had an inhibitory effect on SGC-7901 cell-induced tumors in vivo. The results of the MTT assay suggested that isoimperatorin significantly inhibited the proliferation of SGC-7901 cells in a dose-and time-dependent manner, and the half maximal inhibitory concentration was 18.75 µg/ml. The results of the flow cytometric analysis indicated that, following treatment with isoimperatorin, the apoptotic rate of SGC-7901 cells was significantly increased, compared with that of cells in the control group. The results of the western blot analysis indicated that, following treatment with isoimperatorin, the expression levels of the pro-apoptotic proteins, Bax, c-caspase-3 and c-caspase-9, were significantly increased and the expression levels of the anti-apoptotic proteins, Survivin and Bcl-2, were significantly reduced, compared with the control group. No alterations in expression were found in the other apoptosis-associated proteins, including Mcl-1, Bcl-xl and Smac. The results of the xenograft assay indicated that isoimperatorin significantly inhibited the growth of SGC-7901 cell-induced tumor in vivo by increasing the expression levels of pro-apoptotic proteins (Bax, c-caspase-3 and c-caspase-9) and reducing the expression levels of anti-apoptotic proteins (Survivin and Bcl-2) without adverse effects on the increasing body weight of nude mice. In conclusion, the present study revealed that isoimperatorin may be able to induce the apoptosis of SGC-7901 cells in vitro and in vivo by regulating the expression levels of mitochondria-mediated apoptosis-associated proteins.

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

“…This compound is present in Angelica dahurica, Notopterygium incisum, Ferula lutea, Angelica pubescens, and Peucedanum praeruptorum. Isoimperatorin exhibits various pharmacological activities, including antioxidant [255,256], anti-inflammatory [257], analgesic [258], antibacterial [259,260], and anticancer properties [261,262]. Wijerathne et al reported that isoimperatorin protected against OA-induced asthma via mitigation of airway inflammation and mucus hypersecretion evidenced by the decreased IL-4, IL-5, and IL-13 production [257].…”

Isoimperatorin Induces Apoptosis of Nasopharyngeal Carcinoma Cells via the MAPK/ERK1/2 Signaling Pathway

“…However, significant future research will be needed on related fields in order to better develop the use of traditional Chinese medicines. e previous studies have shown that isoimperatorin effectively inhibits the proliferation of gastric cancer and induces its apoptosis [8][9][10]. Wang Meng [21] also confirmed that isoimperatorin has obvious antitumor activity.…”

“…It has been found in the previous studies that isoimperatorin has a wide range of pharmacological effects as follows: can promote the differentiation of adipocytes; may prevent diabetes [1]; inhibits the activity of melanocytes; promotes the expression of melanin transport related protein Rab27a; reduces the melanocyte melanin content [2,3]; reduces the expression of nitric oxide and tumor necrosis factor-α (TNFα) in fibroblast synovial cells [4]; improves the mitochondrial function; protects the acute liver injury induced by carbon tetrachloride [5]; relaxes the blood vessels [6]; and increases the breast cancer cell radiotherapy sensitivity [7]. Besides, isoimperatorin has anti-inflammatory, analgesic, and antitumor effects and can induce apoptosis as well as inhibit the proliferation of gastric cancer cells [8][9][10]. To date, no reports have examined whether isoimperatorin has an antitumor effect on nasopharyngeal cancer.…”

Pumilaside A from Litchi semen induces apoptosis in human gastric cancer BGC823 cells via activation of death receptor- and mitochondria-mediated apoptotic pathways

“…The BGC823 cells (5 × 10 5 cells/well) were seeded in 12-well plates for 24 h and treated with PA (0, 10, 20 or 40 μg/mL) for 48 h, followed by harvesting and washing (thrice) in chilled PBS, and staining with Annexin V-FITC/PI. The stained cells were then subjected to flow cytometric analysis using FACSCalibur from BD Biosciences (San Jose, CA, USA) [16].…”