<p>Cryptotanshinone inhibits esophageal squamous-cell carcinoma in vitro and in vivo through the suppression of STAT3 activation</p>

Abstract

PurposeEsophageal squamous-cell carcinoma (ESCC) is the most common subtype of esophageal cancer, with a poor clinical outcome. Cryptotanshinone (CTS) is the main bioactive compound from the root of Salvia miltiorrhiza Bunge. Our study aimed to investigate the anti-cancer effects and molecular mechanisms of CTS on ESCC.Materials and methodsWe investigated the anti-tumor activity of CTS on ESCC in vitro and in vivo. Activation of the STAT3 signaling pathway was evaluated in ESCC and HEK-Blue™ IL-6 cells. Cell viability was assessed by the MTT assay. Apoptosis and cell cycle arrest were assessed using flow cytometry. Cell migration was detected by a scratch wound assay.ResultsCTS inhibited STAT3 expression and IL-6-mediated STAT3 activation in esophageal cancer cells. Subsequently, CTS dose-dependently inhibited the proliferation of esophageal cancer cells via induction of cell apoptosis. Furthermore, CTS suppressed the migration of esophageal cancer cells. In vivo, CTS inhibited tumor growth of EC109 cell in xenograft mice without any obvious effect on body weight.ConclusionOur results indicated that STAT3 inhibition may be a therapeutic target for esophageal cancer. CTS could provide a potential approach for esophageal cancer therapy by influencing the janus kinase-2/STAT3 signaling pathway.

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

“…CT induced apoptosis of esophageal EC109 cancer cells by inhibiting p-STAT3 (Tyr705) and p-JAK2 without effect on the expression of the total STAT3 and JAK2 in vitro and in vivo (Ji et al, 2019). It is confirming that the antiesophageal cancer effect of CT was associated with the inhibition of IL-6-mediated activation of JAK2/STAT3 signaling pathway (Ji et al, 2019). Similarly, CT was found to have strong inhibition effects on malignant gliomas (MGs) but also preliminarily explored its potential mechanisms through a series of experiments in vivo and in vitro.…”

“…CT was identified as a potent STAT3 inhibitor that inhibited the phosphorylation of STAT3 Tyr705 and the target proteins such as survivin, Bcl-XL, and cyclin D1 through blocking the dimerization in DU145 prostate cancer cells (Shin et al, 2009). CT induced apoptosis of esophageal EC109 cancer cells by inhibiting p-STAT3 (Tyr705) and p-JAK2 without effect on the expression of the total STAT3 and JAK2 in vitro and in vivo (Ji et al, 2019). It is confirming that the antiesophageal cancer effect of CT was associated with the inhibition of IL-6-mediated activation of JAK2/STAT3 signaling pathway (Ji et al, 2019).…”

JAK/STAT signaling in hepatocellular carcinoma

“…In mice, tumor growth was effectively reduced with CTS treatment, with minimal effects on body weight, indicative of its low toxicity profile. Therefore, CTS has been shown to be a viable alternative for the treatment of esophageal squamous cell carcinoma [89]. In HCC, CTS treatment was found to inhibit the proliferation of mouse hepatoma cells by promoting cell apoptosis via JAK/STAT signaling.…”

Uncovering the Mechanisms of Cryptotanshinone as a Therapeutic Agent Against Hepatocellular Carcinoma

“…For example, CPT reduced inflammation and oxidative stress in renal interstitial fibrosis by modulating the Nrf-2/HO-1 and NF-kappaB signaling pathways ( Wang et al, 2018 ). Additionally, CPT has been reported to exert anticancer effects on multiple types of cancers, including osteosarcoma, lung cancer, esophageal squamous cell carcinoma, colon cancer, ovarian cancer, chronic myeloid leukemia, gastric cancer, breast cancer, renal cell carcinoma, and melanoma ( Chen et al, 2017 ; Pan et al, 2017 ; Wang et al, 2017a ; Dong et al, 2018 ; Yang et al, 2018 ; Zhang et al, 2018b ; Ji et al, 2019 ). In lung cancer cells, CPT exhibits antitumor effects by inhibiting cell proliferation and migration through inhibition of insulin-like growth factor-I (IGF-1)R-mediated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway ( Zhang et al, 2018a ).…”