Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming

Abstract

Objective. Salvianolic acid B (Sal B) has been demonstrated to be a potential chemoprevention agent for several cancers. Herein, we investigated the pharmacological function of Sal B on non-small-cell lung cancer (NSCLC) metastasis. Methods. Two NSCLC cell lines (NCI-H2030 and NCI-H1650) were disposed of by 200 μM Sal B or 10 μM PKM2 agonist TEPP-46. Wound healing and transwell experiments were implemented for analyzing migratory and invasive capacities. Epithelial-to-mesenchymal transition (EMT) markers β-catenin and E-cadherin were measured via western blotting. Cellular bioenergetics were evaluated with glucose uptake, lactate production, enolase activity, cellular ATP levels, as well as seahorse-based oxygen consumption rate (OCR), extracellular acidification rate (ECAR) analysis. Metabolic reprogramming markers PKM2, LDHA, and GLUT1 were detected via western blotting and immunofluorescence. Results. The results showed that Sal B disposal weakened the migration and invasion of NCI-H2030 and NCI-H1650 cells and inactivated the EMT process according to downregulation of β-catenin and upregulation of E-cadherin. Sal B-treated NSCLC cells displayed decreased glucose uptake, lactate production, enolase activity, cellular ATP levels, OCR, and ECAR, indicating a reduction in metabolic reprogramming. Additionally, Sal B downregulated the expression of PKM2, LDHA, and GLUT1. TEPP-46 may reverse the inhibitory effect of Sal B on metastasis as well as metabolic reprogramming. Conclusion. Our findings provide evidence that Sal B enables to weaken NSCLC metastasis through PKM2-independent metabolic reprogramming, which sheds light on the promising therapeutic usage of Sal B in treating NSCLC.

Effect of Thymbra capitata (L.) Cav. on Inflammation, Senescence and Cell Migration

“…Similar effects were reported for rosmarinic acid, promoting cell migration in wound models [148,149] and presenting an inhibitory effect in cancer cells [150][151][152][153][154]. Salvianolic acids A and B are known to induce [155][156][157][158][159] as well as to delay [160][161][162] cell migration. The aglycone apigenin is also reported to promote wound healing in a variety of models [163][164][165][166][167] and to prevent cell migration in cancer cells [168][169][170][171][172][173][174].…”

Salvianolic Acid B: A Review of Pharmacological Effects, Safety, Combination Therapy, New Dosage Forms, and Novel Drug Delivery Routes

“…In addition, it can inhibit EMT and cell migration, hamper cell cycle progression, and induce autophagy and apoptosis in A549 cells [ 37 ]. In the NSCLC cell lines NCI-H2030 and NCI-H1650, salvianolic acid B can inhibit pyruvate kinase M2 (PKM2)-mediated metabolic reprogramming, downregulate the expression of the metabolic reprogramming-related genes lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1), and inactivate EMT (markedly reduced transcription factors β-catenin expression as well as elevated transmembrane glycoproteins E-cadherin expression), thereby attenuating the metastasis of NSCLC [ 38 ].…”

Salvianolic acid B from Salvia miltiorrhiza bunge: A potential antitumor agent

“…Breast cancer is the most common female cancer ( Di Modica et al, 2022 ; Zhang H. et al, 2022 ), with a mortality rate second only to that of lung cancer, especially since the International Agency for Research on Cancer recently found that the mortality rate for breast cancer has now gradually surpassed that of lung cancer ( Pearanpan et al, 2022 ; Yamashita and Kufe, 2022 ). Triple-negative breast cancer is highly malignant and difficult to treat ( Hacking et al, 2022 ; Montalvo-Castro and Salinas-Jazmín, 2022 ).…”