Tenacissoside H Induces Autophagy and Radiosensitivity of Hepatocellular Carcinoma Cells by PI3K/Akt/mTOR Signaling Pathway

Abstract

Tenacissoside H (TEH), which has anti-inflammatory and anti-tumor effects, is a major active ingredient extracted from the stem of Marsdenia tenacissima. However, the effect of TEH on hepatocellular carcinoma (HCC) as well as the underlying mechanisms are still indistinct. Presently, HCC cells (including Huh-7 and HepG2) were dealt with different concentrations of TEH. The proliferation and apoptosis of HCC cells were determined via Cell Counting Kit-8 (CCK8) assay and flow cytometry. In addition, Western blot was conducted to evaluate the expressions of autophagy—and apoptosis-related proteins. Tissue immunofluorescence was carried out to evaluate LC3B expression in the tumor tissues. The data showed that TEH suppressed the growth of HCC cells in a concentration-dependent manner. Besides, TEH enhanced radiosensitivity and promoted the apoptosis of HCC cells. Moreover, the mRNA and protein levels of autophagy-related genes (LC3-II/LC2-I, ATG5, Beclin-1) were significantly promoted by TEH. Mechanistically, TEH attenuated the activation of PI3K/Akt/mTOR signaling pathway. However, inhibition of PI3 K pathway abolished the anti-tumor effects of TEH in HCC cells. Collectively, this study suggested that TEH increases the radiosensitivity of HCC cells via inducing autophagy and apoptosis through downregulating PI3K/Akt/mTOR signaling pathway.

Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

“…In addition, LC3 and Beclin-1 upregulation can lead to the formation of autophagosome [39]. Meanwhile, LC3I is usually converted to LC3II during the formation of autophagosome [40]. More importantly, according to the previous works [41, 42], levels of LC3-II should be compared not to LC3-I but ideally to more than one “housekeeping” protein in autophagy detection and LC3 assays should be evaluated with and without autophagy inhibitor (3-MA) [27].…”

IKK/NF‐κB and ROS signal axes are involved in Tenacissoside H mediated inhibitory effects on LPS‐induced inflammatory osteolysis

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Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives

“…xenograft tumor model (Ye et al, 2018). Moreover, tenacissoside H, an active natural component derived from Marsdenia tenacissima, was shown to promote autophagy in Huh-7 and HepG2 cells by attenuating the activation of PI3K/Akt/mTOR signaling pathway, as well as promoting the expression of ATGs (LC3-II/LC2-I, ATG5, and Beclin-1), while also in vivo reduced the volume of HCC tissues (Lin et al, 2021). Furthermore, shikonin is a natural small molecule compound shown to induce apoptosis and autophagy by reducing the expression of pyrroline-5-carboxylate reductase 1 (PYCR1) and inhibiting PI3K/Akt/mTOR (Zhang, Shang, et al, 2022).…”

“…Studies have shown that Brusatol, an active natural ingredient isolated from the traditional herbal medicine Bruceae Fructus, can activate autophagy by inhibiting the PI3K/Akt/mTOR pathway and is able to effectively inhibit the proliferation and induce apoptosis of HCC in Bel7404 cells and Bel7404 xenograft tumor model (Ye et al, 2018). Moreover, tenacissoside H, an active natural component derived from Marsdenia tenacissima , was shown to promote autophagy in Huh‐7 and HepG2 cells by attenuating the activation of PI3K/Akt/mTOR signaling pathway, as well as promoting the expression of ATGs (LC3‐II/LC2‐I, ATG5, and Beclin‐1), while also in vivo reduced the volume of HCC tissues (Lin et al, 2021). Furthermore, shikonin is a natural small molecule compound shown to induce apoptosis and autophagy by reducing the expression of pyrroline‐5‐carboxylate reductase 1 (PYCR1) and inhibiting PI3K/Akt/mTOR (Zhang, Shang, et al, 2022).…”