Effects of isoimperatorin on proliferation and apoptosis of human gastric carcinoma cells

Abstract

Resistance to apoptosis is an characteristic of cancer cells that serves a critical function in tumor development and represents a target for antitumor therapy. Isoimperatorin (ISOIM), a coumarin compound, exhibits antitumor functions in multiple types of tumor cells. However, its antitumor effects and molecular mechanisms with respect to gastric cancer have not been elucidated. The present study assessed the anti-proliferative and apoptotic effects of ISOIM on human BGC-823 gastric cancer cells and elucidated its underlying molecular mechanisms. Cell proliferation was evaluated using MTT assays. Analysis of cell morphology was performed by hematoxylin and eosin, Hoechst 33258 and acridine orange/ethidium bromide staining. In addition, cell cycle and apoptosis was evaluated using flow cytometry analysis; expression of apoptosis-associated proteins was studied by western blotting. The results of the present study revealed that ISOIM significantly inhibited cell proliferation by arresting the cell cycle at the G/M phase and induced apoptosis by increasing Bcl-2-associated X (Bax) expression with a concomitant decrease in Bcl-2 expression, resulting in a decreased Bcl-2/Bax ratio compared with the control. In addition, ISOIM treatment also resulted in cytochrome translocating from the mitochondria to the cytosol. Furthermore, caspase-3 was significantly activated in response to treatment with ISOIM, suggesting that apoptosis in BGC-823 cells is induced in the mitochondrial pathway. Taken together, the results of the present study indicate that ISOIM may significantly induce apoptosis in BGC-823 cells and that the pro-apoptotic mechanisms of ISOIM could be associated with the mitochondrial pathway.

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].…”

Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma

“…Plants usually contain a variety of anti-tumor compounds, and many plant extracts have been used in the treatment of cancer such as vincristine, paclitaxel and topotecan [40][41][42]. ISOIM is an active compound extracted from Chinese herbal medicine, which has been shown to possess anti-tumor properties in gastric, lung and ovarian cancer cells [9].…”

“…In this regard, Kim YK et al found that ISOIM has different inhibitory effects on human lung cancer cell line A549 as well as human ovarian cancer cell line SK-OV-3 in a dose-dependent manner [7]. In addition, studies have shown that ISOIM can inhibit the proliferation and promote apoptosis of human gastric cancer cells [8,9]. However, most anticancer drugs are low molecular weight compounds that are easily excreted via glomerular filtration or liver metabolism [10].…”

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

“…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.…”