Emodin induces apoptosis of lung cancer cells through ER stress and the TRIB3/NF-κB pathway

Abstract

Emodin is a phytochemical with potent anticancer activities against various human malignant cancer types, including lung cancer; however, the molecular mechanisms underlying the effects of emodin remain unclear. In the present study, the A549 and H1299 human non-small lung cancer cell lines were treated with emodin and the induced molecular effects were investigated. Changes in cell viability were evaluated by MTT assay, Hoechst staining was used to indicate the apoptotic cells, and western blotting was utilized to assess endoplasmic reticulum (ER) stress and signaling changes. RNA interference was also employed to further examine the role of tribbles homolog 3 (TRIB3) in the emodin-induced apoptosis of lung cancer cells. Emodin was found to reduce the viability of lung cancer cells and induce apoptosis in a concentration-dependent manner. Emodin-induced apoptosis was impaired by inhibition of ER stress using 4-phenylbutyrate (4-PBA). ER stress and TRIB3/nuclear factor-κB signaling was activated in emodin-treated lung cancer cells. Emodin-induced apoptosis was reduced by TRIB3 knockdown in A549 cells, whereas ER stress was not reduced. In vivo assays verified the significance of these results, revealing that emodin inhibited lung cancer growth and that the inhibitory effects were reduced by inhibition of ER stress with 4-PBA. In conclusion, the results suggest that TRIB3 signaling is associated with emodin-induced ER stress-mediated apoptosis in lung cancer cells.

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

“…In a BALB/c nude mice, emodin (50 mg/kg) inhibited the growth of human lung epithelial (A549) cells by inducing endoplasmic reticulum (ER) stress-dependent apoptosis. The in vitro molecular mechanism showed that emodin activated ER stress and TRIB3/nuclear factor-kB signaling (Su et al, 2017). In mice bearing EO771 or 4T1 breast tumors, emodin suppressed tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T-cell activation and reduced tumor angiogenesis (Iwanowycz et al, 2016).…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Emodin induces apoptosis through the loss of mitochondrial membrane potential, modulation of Bcl-2 family proteins, and caspase activation in human colorectal cancer CoCa cells and hepatocellular carcinoma HepaRG cells [381,390]. ER stress is activated in emodintreated human osteosarcoma U2OS cells, and emodininduced apoptosis is suppressed by ER stress inhibition with 4-phenylbutyrate (4-PBA) in human NSCLC A549 and H1299 cells [391,393].…”

Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase‑dependent pathway

“…1) is a naturally occurring anthraquinone derivative, which is found in a variety of tradition Chinese herbs including Rheum palmatum (9), Polygonum cuspidatum (10), Polygonum multiflorum (11) and Cassia occidentalis (12). Modern pharmacological studies have revealed that emodin possesses anti-proliferative effects on various cancer cells, such as pancreatic cancer (13), breast cancer (14), hepatocellular carcinoma (15), lung carcinoma (16), gastric carcinoma (17) and prostate cancer (18). Furthermore, this drug has also been reported to exhibit antiviral (19), antibacterial (20), anti-allergic (21), anti-osteoporotic (22), anti-diabetic (23), immunosuppressive (24) and neuroprotective (25) activities.…”