Scutellarin improves the radiosensitivity of non‐small cell lung cancer cells to iodine‐125 seeds via downregulating the AKT/mTOR pathway

Abstract

Background: In our previous study, we indicated that scutellarin (SCU) induced an anticancer effect in A549 cells. However, whether SCU regulates the radiosensitivity of non-small cell lung cancer (NSCLC) and its related mechanism is still unclear. Methods: In this study, we explored the anticancer effect induced by iodine-125 ( 125 I) and SCU at a sensitizing concentration in A549 and H1975 cells. Cellular apoptosis and proliferation were detected by flow cytometry, Bcl-2/Bax expression level, cell cycle, CCK-8, and EdU staining. A tumor model using nude mice was also carried out to investigate the combined effect of 125 I and SCU in vivo. In addition, the expression level of AKT/mTOR pathway was detected to investigate whether it is linked to the anticancer effect of 125 I and SCU.Results: SCU at a sensitizing concentration promoted the 125 I-induced apoptosis and antiproliferative effect in A549 and H1975 cells. Moreover, the same results were obtained in vivo. Based on our findings, the AKT/mTOR pathway was significantly downregulated after combined treatment with 125 I and SCU. Conclusions: The results of our study suggested that SCU promotes the anticancer effects induced by 125 I in NSCLC cells by downregulating the AKT/mTOR pathway and lays a foundation for future application of this combined treatment.

Induction of RIPK3/MLKL-mediated necroptosis by Erigeron breviscapus injection exhibits potent antitumor effect

“…Recent studies have suggested that the active ingredients in EBI have potential antitumor effects. SCU has been shown to have potent antitumor properties against various types of cancer, such as non-small cell lung cancer (NSCLC) (He et al, 2021), colorectal cancer (Tan et al, 2020), kidney cancer (Deng et al, 2018), bladder cancer (Lv et al, 2019), and liver cancer (Ke et al, 2017), due to its ability to arrest the cell cycle, induce cell apoptosis, inhibit cell proliferation, and reverse epithelial-mesenchymal transition. Moreover, caffeoylquinic acid esters have been shown to promote cancer cell apoptosis, suppress tumor growth, and hinder metastasis through diverse molecular mechanisms (Puangpraphant et al, 2011;Zhou et al, 2020).…”

Current advances on the therapeutic potential of scutellarin: an updated review

“…However, scutellarin modulates this pathway to induce apoptosis in tumor cells, and it has been reported that scutellarin selectively reduces the survival rate of tumor cells without affecting normal cells [ 50 – 53 ]. He and others [ 54 ] found that scutellarin could enhance 125 I-induced apoptosis and the antiproliferative effect of tumor cells through down-regulation of the AKT/mTOR pathway, which provided the possibility of its combination therapy. Sun and others [ 55 ] found that scutellarin could promote caspase-3-dependent apoptosis induced by the first-line antitumor drug cisplatin via the ERK/P53 pathway and promote cisplatin-induced cytotoxicity autophagy via the c-Met-AKT pathway, which in turn acted to reverse the unique properties of cisplatin resistance.…”

Scutellarin Inhibits Glioblastoma Growth in a Dose-dependent Manner by Suppressing the p63 Signaling Pathway

“… 9 Scutellarin inhibits proliferation and metastasis, induces cell apoptosis and differentiation of cancer cells, and plays anti-neoplastic roles in gastric cancer, 10 colon cancer, 11 and non-small cell lung cancer (NSCLC). 12 However, the influences of scutellarin on GBM, as well as the underlying mechanisms, are still unclear. 13 In this study, we investigated the anti-tumor effect of scutellarin on GBM in in vitro cell models and revealed the possible mechanisms by combining next-generation sequencing with confirmation via Western blotting and qRT‒PCR.…”