Osteosarcoma cell proliferation suppression via SHP-2-mediated inactivation of the JAK/STAT3 pathway by tubocapsenolide A

Abstract

Graphical abstract

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

“…Hederoside C P. koreana MG-63, U2OS [100] Salidroside Rhodiola rosea L. U2OS, MG-63 [101] Tubocapsenolide A Tubocapsicum anomalum SHP-2 [102] Andrographolide Andrographis paniculata U2OS [103] Pacilitaxel Taxus wallichiana var. chinensis (Pilger) Florin U2OS, MG-63 [104] Resveratrol Veratrum album MNNG/HOS, MG-63 [105] β-caryophyllene Dianthus chinensis L. MG-63 [106] Sodium cantharidate Mylabris phalerata Pallas MG-63 [107] Tanshinone I Salvia miltiorrhiza Bunge U2OS, MOS-J [108,109] Notch pathway Cinobufagin Bufo raddei U2OS, MG-63 [110] Curcumin Curcuma longa L. U2OS [92,111] Cannabinoids Cannabis sativa L. MG-63 [112] Dihydroartemisinin Artemisia caruifolia Buch.-Ham.…”

“…Agrimonia lactone is a lactone-containing steroid extracted from the traditional Chinese herbal medicine Agrimonia pilosa and has attracted much attention of researchers, because it has shown effective anti-proliferative activity in several cancer cell lines. Zhu et al [102] found that agrimonia lactone activated the phosphatase activity of Src homology 2 phosphatase 2 (SHP-2), thereby inhibiting the JAK/STAT3 signaling pathway, helping to inhibit the proliferation of OS cells and promote the apoptosis of OS cells. Andrographolide has the effects of clearing heat and detoxicatin, reducing inflammation and relieving pain, while Cai et al [103] found that this compound could reduce the phosphorylation level of STAT1/2 by inhibiting the activity of JAK2/STAT3 signaling pathway, reduce the release of pro-inflammatory cytokines or mediators (including TNF-α, IL-6, IL-1βand IL-10), so as to reduce the degree of paw swelling in mice, and block the progression of OS.…”

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

“…Only a few studies have evaluated the role of JAK in OS. In recent years, the JAK/STAT3 signaling pathway has been extensively studied, and researchers have proven that inappropriate activation of JAK/STAT3 in OS is always linked to physiological events such as defective tumor cell migration, invasiveness, metastasis, and vascular neogenesis 105,106 …”

“…The curcumin analog L48H37 lowered the phosphorylation level of JAK3, STAT3, JAK2, and JAK1 in U2OS cells, thereby inhibiting the invasion and migration of these cells 280 . Tubocapsenolide A inhibits OS cell proliferation through SHP‐2‐induced JAK/STAT3 pathway inactivation 105 . β‐Caryophyllene regulates the JAK1/STAT3 signaling pathway in MG63 cells through the ROS‐induced apoptotic DNA fragmentation mitochondrial pathway, thereby promoting OS cells apoptosis and inflammation 281 .…”

“…In recent years, the JAK/STAT3 signaling pathway has been extensively studied, and researchers have proven that inappropriate activation of JAK/STAT3 in OS is always linked to physiological events such as defective tumor cell migration, invasiveness, metastasis, and vascular neogenesis. 105,106 OS cell lines highly express STAT3 and p-STAT3, and inhibition of STAT3 activation can downregulate Cyclin D1 expression and further inhibit the proliferative ability of OS cells. [107][108][109] The long-chain noncoding RNA HOXD-AS1 increases the levels of matrix metalloproteinases (MMP-2), Bcl-2, and Cyclin D1 through the upregulation of STAT3 and its activity, thus achieving a proproliferative effect on OS.…”