Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway

Abstract

Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant, Sinomenium acutum , showed that it had inhibitory effects on several kinds of cancer. Here, we synthesized a sinomenine derivative, sino-wcj-33 (SW33), tested it for antitumor activity on GBM and explored the underlying mechanism. SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells. It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis. Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body. SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR pathways. Thus, SW33 appears to be a promising drug for treating GBM effectively and safely.

Sinomenine promotes differentiation of induced pluripotent stem cells into immature dendritic cells with high induction of immune tolerance

“…It has been reported that SN can stimulate the differentiation of peripheral blood mononuclear cells into imDCs and further inhibit the maturation of imDCs[ 13 ]. SN can reduce the expression of CCR5 and CCR7 on DCs, inhibit secretion of chemokines CXCL9 and CXCL10, block expression of TLR2 and TLR4 in peripheral blood DCs, stimulate differentiation of monocytes into imDCs, and inhibit their further maturation[ 33 ]. Due to the mild drug properties of SN, short half-life, lack of toxicity below a certain dose, and lack of mutagenicity, the compound was used to induce bone marrow stem cells to differentiate into imDCs (SN-BM-imDCs).…”

“…The results indicate that imDCs phagocytose apoptotic DCs, transform into tolerance DCs, and then induce naïve T cells to differentiate into FoxP3 + Treg cells[ 34 ]. Some studies have also confirmed that SN could inhibit glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway[ 33 , 34 ]. However, there is no report on SN-induced apoptosis of DCs.…”

Azadirachtin Attenuates Lipopolysaccharide-Induced ROS Production, DNA Damage, and Apoptosis by Regulating JNK/Akt and AMPK/mTOR-Dependent Pathways in Rin-5F Pancreatic Beta Cells

“…Similarly, caspase-3-induced cleavage of autophagy-related proteins also induces apoptosis [ 58 ]. Autophagy has also been shown to be mutually associated and regulated by the cell cycle [ 59 , 60 ].…”

Natural medicines of targeted rheumatoid arthritis and its action mechanism

“…Sinomenine is the main active ingredient isolated from the Chinese medicinal Caulis Sinomenii for the treatment of rheumatic diseases, and has the biological effects of anti-inflammation, anti-oxidation, inhibition of apoptosis, immunosuppression, etc ( 56 – 58 ). Clinical studies have shown that ( 59 , 60 ) sinomenine has a significant effect on the treatment of RA.…”