β-Patchoulene represses hypoxia-induced proliferation and epithelial-mesenchymal transition of liver cancer cells

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor originating from liver epithelial cells with a high clinical mortality rate. β-Patchoulene (β-PAE) is a compound extracted from patchouli, which has analgesic, anti-inflammatory and antioxidant effects. This research aims to probe the impacts of β-PAE on hypoxia-induced HCC cell proliferation and epithelial-mesenchymal transition (EMT). Firstly, hypoxic injury models were constructed in HCC Huh-7 and MHCC97 cells, and the hypoxic injury cell models were then treated with different concentrations of β-PAE. The cell viability, proliferation, migration, invasion and apoptosis were checked by the cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay, flow cytometry and terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of Survivin protein, EMT markers and the NF-κB/HIF-1α pathway was gauged by Western blot (WB) or cellular immunofluorescence or reverse transcription-polymerase chain reaction (RT-PCR). The in-vivo experiment was conducted to confirm the anti-tumor role of β-PAE. As a result, β-PAE abated hypoxia-induced HCC cell growth, proliferation, migration, invasion and EMT and facilitated apoptosis in vitro and in vivo dose-dependently. Further mechanism studies displayed that β-PAE inactivated the NF-κB/HIF-1α pathway, and HIF-1α activation significantly reversed the β-PAE-mediated tumor inhibition. β-PAE repressed the proliferation and EMT of hypoxia-induced HCC cells by choking the NF-κB/HIF-1α pathway, suggesting that β-PAE was a potential drug for HCC treatment.

Network analysis to explore the pharmacological mechanism of Shenmai injection in treating granulocytopenia and evidence-based medicine approach validation

“…Research has demonstrated that both β-patchoulene and ginsenoside have anti-tumor properties. [31][32][33] These discoveries suggests that there may be potential clinical uses for shenmai injection. By leveraging these components, it may be possible to mitigate some of the undesirable side effects of radiotherapy and chemotherapy, thus improving the granulocytopenia caused by myelosuppression.…”

Wnt/β-catenin-driven EMT regulation in human cancers

“…Decrease in N-cadherin and vimentin levels, and increase in E-cadherin levels can be observed after administration of β-elemene in inhibiting EMT in colorectal tumor [ 56 ]. As mentioned, hypoxia is involved in EMT induction and facilitated cancer invasion which can be overcome by β-patchoulene [ 57 ]. Moreover, there is a close association between EMT induction and drug resistance in human cancers [ 58 ].…”

Morinda officinalis polysaccharide promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via microRNA-210-3p/scavenger receptor class A member 3

“…The hBMSCs were cultured in a-MEM medium (Gibco, Carlsbad, CA, USA) containing 10% fetal bovine serum (FBS, Gibco, USA), 100 U/ml penicillin and 100 mg/L streptomycins in 5% CO 2 at 37°C. 16 When reaching 70%-80% confluency, the cells were sub-cultured to the next generation using trypsin (Beyotime Biotechnology, Shanghai City, China), and hBMSCs of the 3rd-5th generation were used for subsequent experiments.…”

“…For osteoblast differentiation, hBMSCs were cultured in 24-well plates using an osteogenic induction medium (a-MEM medium, 10% FBS, 50 mg/mL ascorbic acid, 0.1 mg/L dexamethasone, as well as 10 mmol/L b-glycerophosphate [Sigma-Aldrich, Louis, MO, USA]), for 8 days to induce them into osteoblasts. 16,17 For adipogenic differentiation, the cells were cultured in medium A (Cyagen, Guangdong, China) for 3 days and adipogenic differentiation medium B (Cyagen, Guangdong, China) for 1 day in turn. 16,17 Extraction and preparation of MOP…”

“…16,17 For adipogenic differentiation, the cells were cultured in medium A (Cyagen, Guangdong, China) for 3 days and adipogenic differentiation medium B (Cyagen, Guangdong, China) for 1 day in turn. 16,17 Extraction and preparation of MOP…”