Anticancer effects and the mechanism underlying 2‑methoxyestradiol in human osteosarcoma <em>in&nbsp;vitro</em> and <em>in&nbsp;vivo</em>

Abstract

Osteosarcoma (OS) occurs in both children and adolescents and leads to a poor prognosis. 2-methoxyestradiol (2-ME) has a strong antitumor effect and is effective against numerous types of tumor. However, 2-ME has a low level of antitumor effects in OS. The present study investigated the effects of 2-ME on the proliferation and apoptosis of human MG63 OS cells. The potential biological mechanisms by which 2-ME exerts its biological effects were also investigated in the present study. The results of the present study demonstrated that 2-ME inhibited the proliferation of OS cells in a time-and dose-dependent manner, induced G 2 /M phase cell cycle arrest and early apoptosis. The expression levels of vascular endothelial growth factor (VEGF), Bcl-2 and caspase-3 were measured via western blotting and reverse transcription-quantitative PCR. As the concentration of 2-ME increased, the RNA and protein expression levels of VEGF and Bcl-2 decreased gradually, whereas the expression of caspase-3 increased gradually. In addition, tumor growth in nude mice was suppressed by 2-ME with no toxic side effects observed in the liver or kidney. Immunohistochemistry demonstrated that the expression levels of Bcl-2 and VEGF were significantly lower, and those of caspase-3 were significantly higher in test mice compared with the control group. TUNEL staining of xenograft tumors revealed that with increased 2-ME concentration, the number of apoptotic cells also gradually increased. Thus, 2-ME effectively inhibited the proliferation and induced apoptosis of MG63 OS cells in vitro and in vivo with no obvious side effects. The mechanism of the anticancer effect of 2-ME may be associated with the actions of Bcl-2, VEGF and caspase-3.

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

“…A previous study showed that at least 10 μM of 2ME was required to increase caspase-3 and the increase was gradual as well. This demonstrates that the intrinsic-mediated caspase-3 activation pathway is involved in 2ME mediated apoptosis (Tang et al., 2020 ). We reported that 2ME-INVA-APA downregulated the expression of both TNF-α and NF-κB.…”

Effect of 2‐methoxyestradiol on mammary tumor initiation and progression

“…Numerous studies in BC, both in vitro and in vivo. have demonstrated that 2‐ME has anti‐angiogenic and anti‐proliferative properties 14–21 . Moreover, the use of 2‐ME has been shown to enhance the effects of chemotherapy in the treatment of BC 22 .…”

“…have demonstrated that 2‐ME has anti‐angiogenic and anti‐proliferative properties. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 Moreover, the use of 2‐ME has been shown to enhance the effects of chemotherapy in the treatment of BC. 22 For example, combining 2‐ME with paclitaxel, a widely used chemotherapy drug, has been shown to improve treatment outcomes in preclinical models of BC.…”