Application of eupatilin in the treatment of osteosarcoma

Abstract

Abstract. 5,7-dihydroxy-3' ,4' ,6-trimethoxyflavone, commonly known as eupatilin, is a traditional Asian medicinal plant, which is mainly used for the treatment of gastritis, as well as its use as an anti-inflammatory agent. Eupatilin is a bioactive compound; however, its effects on osteosarcoma (OS) have remained to be elucidated. Therefore, the present study aimed to investigate the effects of eupatilin on this malignant bone tumor, using the U-2 OS cell line. The experimental results revealed that eupatilin inhibited U-2 OS cell growth in a concentration-dependent manner and induced G2/M phase cell cycle arrest and apoptosis. Additionally, western blot analysis indicated that eupatilin was able to trigger the mitochondrial apoptotic pathway, demonstrated by the enhanced Bax/B cell lymphoma-2 ratio, decrease in mitochondrial membrane potential, release of cytochrome c, caspase-3 and -9 activation and poly(ADP-ribose)polymerase cleavage detected in the U-2 OS cells. These results indicated that eupatilin was able to inhibit U-2 OS cancer cell proliferation by the induction of apoptosis via the mitochondrial intrinsic pathway. Eupatilin may therefore represent a novel anticancer drug for use in the treatment of osteosarcoma. IntroductionOsteosarcoma (OS) is considered to be one of the most common and aggressive primary bone tumors of the musculoskeletal system, and predominantly occurs in childhood and adolescence (1,2). There are various potential treatments for OS, including radiotherapy, surgery and chemotherapy; however, the results of these available treatments remain unsatisfactory (3). Significant nephrotoxic and cardiotoxic side-effects are induced by chemopreventative medicines, thereby limiting the efficacy of their use in the treatment of OS (4). Manipulation of apoptosis is one of the major targets in the treatment of cancer.Apoptosis describes genetically-dependent programmed cell death type I, and is characterized by cell shrinkage, signal transduction (5), nucleic condensation (6,7) and DNA and cellular protein degradation (8). Previous studies have revealed that few therapeutic treatments exist that result in an enhanced ability of human tumor cell lines to undergo apoptosis (9,10). Therefore, the development of novel agents to induce or increase the phenomenon of apoptosis present a promising approach for the development of cancer treatments. Novel inducers of apoptosis may provide alternative and efficacious therapeutic anticancer strategies.Flavonoids are associated with multiple biological effects, including antitumor, anti-oxidation, anti-inflammation, antiviral and hepatoprotective activities, as well as in the prevention of cardiovascular diseases (11-16). Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is extracted from Artemisia asiatica (A. asiatica) Nakai, and this isolated flavonoid contains pharmacologically active ingredients. Eupatilin has been demonstrated to exert anticancer, anti-oxidative and anti-inflammatory effects (17). A previous report indicated that Stillen™ (DA-9601...

Eupatilin regulates proliferation and cell cycle of cervical cancer by regulating hedgehog signalling pathway

“…Previous study had revealed the anti‐proliferation and apoptosis induction mechanisms of eupatilin involved in mitochondrial intrinsic pathway of osteosarcoma cells . Similarly, herein, we explored the functions of eupatilin in regard to proliferation inhibition, cell cycle arrest, and apoptosis induction in cervical cancer.…”

“…In addition, eupatilin has shown anti‐diabetic, anti‐arthritis, and anti‐proliferative activity. Importantly, eupatilin's anti‐cancer properties have been found in multiple cancers, including human oesophageal cancer, renal cancer, glioma, osteosarcoma, and gastric cancer . However, no literature has explored the role of eupatilin in cervical cancer.…”

Eupatilin Inhibits Renal Cancer Growth by Downregulating MicroRNA-21 through the Activation of YAP1

“…Eupatilin has an inhibitory effect on a variety of tumors. Eupatilin induces apoptosis of osteosarcoma U-2OS cells through mitochondrial endogenous pathways and inhibits the proliferation of osteosarcoma cells [18]. Eupatilin has a significant therapeutic effect on gastric cancer, and it inhibits the growth of gastric cancer cells by blocking STAT3-mediated vascular endothelial growth factor expression [19].…”

Herbal Remedy for Osteosarcoma - Challenging Evolution

“…Western blot analysis indicated that it was able to cause the mitochondrial apoptotic pathway, by the enhanced Bax/Bcl-2 ratio, decrease in mitochondrial membrane capability, the release of cytochrome c, caspase-3 and -9 activation and PAPR cleavage detected in the U2-OS cells. Hence, eupatilin may, therefore, represent a novel anticancer drug for use in the treatment of OS [33].…”