Hedyotis diffusa Willd. Suppresses Hepatocellular Carcinoma via Downregulating AKT/mTOR Pathways

Abstract

Objective. Hedyotis diffusa Willd. (HDW) is a famous Chinese herbal medicine, traditionally used to treat cancer in China. Currently, the clinically used drugs for the treatment of hepatocellular carcinoma (HCC) still have poor efficacy and have many side effects. HDW has fewer side effects after taking it, so this study explores the inhibitory effect of HDW on HCC, which may become a promising drug for the treatment of HCC. Methods. HCC cell lines such as SMMC-7721, SK-hep1, and Hep-G2 were treated with Hedyotis diffusa Willd. (HDW), after which migration was detected via transwell, while the proliferation of these cells was detected via MTT, CCK-8, and colony formation assays. Furthermore, protein levels were evaluated by western blotting, and Hep-G2 cells were implanted in nude mice to establish a xenograft model to evaluate the antitumor effect of the drug. Results. HDW exhibited the ability to inhibit the proliferation and migration of HCC cells. And its anticancer mechanism in hepatocellular carcinoma may be via AKT/mTOR pathway. Moreover, the drug use of HDW in the mouse model system has achieved a good effect. Importantly, it did not cause significant weight loss or hepatorenal toxicity. Conclusion. HDW can suppress the activation of the AKT/mTOR pathway in HCC cells, which may bring new light for the treatment of this kind of malignant tumor, but its exact mechanism still needs to be further explored.

Total flavonoids of Oldenlandia diffusa (Willd.) Roxb. suppresses the growth of hepatocellular carcinoma through endoplasmic reticulum stress-mediated autophagy and apoptosis

“…Our study sought to verify that FOD can induce apoptosis and autophagy by activating the ER stress pathway in hepatocellular carcinoma. In this study, FOD reduced the volume of subcutaneous tumor in mice and inhibited the proliferation, which was consistent with the previous results obtained by Huang et al in the HepG2 xenograft subcutaneous tumor mouse model ( Huang et al, 2021 ). At the same time, we also found that FOD reduced the inflammatory indicators (IL-6, TNFα) in the blood of mice.…”

“…FOD are the main active components of Hedyotis diffusa Willd ( Chen et al, 2016a ; Qian et al, 2021 ). Previous studies have found that FOD can inhibit the proliferation of HCC cells, block the G0/G1 cell cycle, induce apoptosis, and down-regulate AKT/mTOR and CDK2-E2F1 pathways in HCC cells, and inhibit the growth of mouse xenograft tumors ( Chen et al, 2012 ; Chen et al, 2020 ; Huang et al, 2021 ). Our study sought to verify that FOD can induce apoptosis and autophagy by activating the ER stress pathway in hepatocellular carcinoma.…”

“…Although FOD can inhibit the proliferation and induce apoptosis of HCC cells ( Huang et al, 2021 ) ( Yang et al, 2021 ), the mechanism underlying its cytotoxicity to HCC cells and the role of reticulum (ER) stress remain unclear. Therefore, we investigated whether HDW induces autophagy and apoptosis through ER stress-signalling pathways in HCC cells.…”

Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway

“…Mounting evidence showed that SBD had an inhibitory effect on lung cancer, liver cancer, leukemia, and breast cancer [ 5 , 12 – 14 ]. At the same time, it has been reported that Hedyotis diffusa Willd (HD) had positive effect on the treatment of malignant tumor [ 15 , 16 ]. These studies have been indicated that SBD is a potential drug in anti-tumor treatment.…”

Molecular Mechanism of Anti-Colorectal Cancer Effect of Hedyotis diffusa Willd and Its Extracts

“…Early pharmacological studies have confirmed that HDW has medicinal properties like antitumor, anti-inflammatory, immunomodulatory, antioxidant, and other biological activities ( Shen et al, 2016 ). As an antitumor herbal medicine, HDW and its extracts have been widely used in the treatment of CRC, breast cancer, prostate cancer, and so on ( Wazir et al, 2021 ; Huang et al, 2021 ). In this review, we explore the advantages, potential signal pathways, and representative active ingredients of HDW in the treatment of CRC.…”