Anti-tumor Effect of Polysaccharides From Scutellaria Barbata D. Don on the 95-D Xenograft Model via Inhibition of the C-Met Pathway

Abstract

Abstract. Polysaccharides isolated from Scutellaria barbata (PSB) have been reported to have anti-tumor effects. To investigate the underlying mechanism, a highly invasive, metastatic and phospho-c-Met overexpression lung carcinoma cell, 95-D cell line was used. The results showed that in vitro, PSB not only could inhibit the proliferation of 95-D cell line (IC 50 = 35.2 mg/mL), but also down-regulated the expression of phospho-c-Met and its downstream signaling molecules including phospho-Erk and phospho-Akt. In vivo, PSB inhibited tumor growth in the 95-D subcutaneous xenograft model in a dose-dependent manner; after once-daily intraperitoneal injection for 3 weeks, tumor growth inhibition T/C ratio for 100 and 200 mg/kg treatments was 42.72% and 13.6%, respectively. In the end of the in vivo study, tumor tissues were harvested for further evaluation of the phosphorylation level of c-Met, AKT, and ERK. Ex vivo results demonstrated that the phosphorylation of c-Met and its downstream signaling molecules were also significantly inhibited by PSB. Immunohistochemistry analysis showed dose-dependent inhibition of tumor cell proliferation (Ki67) and reduction of microvessel density (CD31). In summary, the results indicated that PSB exerted anti-tumor growth activity on human lung cancer 95-D in vitro and in vivo by directly regulating the c-Met signaling pathway and the anti-tumor effects were mainly based on its anti-proliferation and anti-angiogenesis action.

Characterization and quantification of the chemical compositions of Scutellariae Barbatae herba and differentiation from its substitute by combining UHPLC–PDA–QTOF–MS/MS with UHPLC–MS/MS

“…Modern pharmacological studies have showed that S. barbata (SB) has a wide variety of medical applications due to its antioxidant, anticancer, as well as anti-angiogenic effects, etc. [2][3][4]. Phytochemistry research found that flavonoids constituents, such as scutellarin, naringenin, apigenin, luteolin and wogonin, are the main effective components of SB [5][6][7][8][9].…”

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

“…One of Traditional Chinese medicines (TCMs), Scutellariabarbata D. Don extraction (SBE) have been being applied independently or combined with modern medicine to improve symptoms, enhance quality of life, prevent recurrence and metastasis, and prolong survival in cancer patients in China for many years 21, 22, 25, 33, 34 . In our studies, SBE significantly inhibited the in vitro growth of human non-small cell lung cancer A549 and H1299 cells in dose-dependent manners.…”

“…Scutellariabarbata D. Don extraction (SBE), as one of TCMs, has been being used in China for many years as an efficacious anti-cancer drug 22–25 . SBE is reported recently to induce cancer cell apoptosis by activating the mitochondrion-dependent pathway, to repress tumor angiogenesis via suppression of Hedgehog signaling, and to enhance G1/S arrest in human colon carcinoma cells by modulating a number of signaling pathways associated with the cell cycle 22, 26–28 .…”

Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research

“…However, increased efficacy against lung cancers was noted by P3 because S. barbata is thought to have affinity for the lung meridian. Several recent laboratory studies on lung cancer have identified notable anticancer effects on a variety of lung cancer cell lines (Yang et al, 2015;Shiau et al, 2014;Yang et al, 2014;Gong et al, 2015). One Western study noted that S. barbata extract had greater than 50% inhibition for human lung carcinoma (A549), but also found that S. barbata was more effective against human breast adenocarcinoma (MCF-7) (Shoemaker et al, 2005).…”