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

Abstract

Background Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer. Materials and methods CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs. Results The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues. Conclusions Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients.

The use of network pharmacology to investigate the mechanism of action of Scutellaria barbata in the treatment of prostate cancer

“…Over recent years, studies have shown that Scutellaria barbata and its active ingredients have obvious therapeutic effects on prostate cancer, and its extract has been used in mechanistic research relating to the treatment of prostate cancer [24,25]. Scutellaria barbata B is a diterpene alkaloid compound extracted from Scutellaria barbata, that can inhibit the progression of human prostate carcinogenesis cells in a dosedependent manner, thus treating the aggression and metastasis of prostate cancer [26].…”

Chinese herbal medicines for prostate cancer therapy: From experimental research to clinical practice

“… Chinese names Scientific names Extraction solvents Effects Mechanisms References Chonglou Paridis Rhizoma Ethanol Induce apoptosis and cell cycle arrest Induce G2/M arrest of PC3 cells and G0/G1 arrest of both PC3 and DU145 cells Zhang et al, 2018 Lingzhi Ganoderma Ethanol Suppress cell growth and metastatic capability, cause cell cycle arrest, and induce apoptosis Block the PI3K/Akt and MAPK/ERK signaling pathways Huang et al, 2019 Huaier Trametes robiniophila Murr. Aqueous Suppress proliferative and metastatic Downregulate Lamin B1 Yang et al, 2018 Inhibit cell growth and overcome drug resistance Inhibit AR-FL/AR-V7 signaling pathways Liu et al, 2021 Banzhilian Scutellariae Barbatae Herba Ethanol Induce cell apoptosis and cell cycle arrest Inactivate PI3K/AKT signalling pathway Sheng et al, 2022 Buguzhi Psoraleae Fructus Ethanol Induce apoptosis, autophagy, alter genes expression and cell cycle regulation Increase injurious genes DDIT3, AVEN, BAG2, and ANXA1, decrease cell cycle-associated genes, SKP2, CDCA3, CDCA2, GTSE1, CDCA7, CDCA7L, and CDC7 Hnit et al, 2020 …”

“…In vitro and in vivo , Scutellariae Barbatae Herba induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signaling pathway. It has the potential to exhibit anti-angiogenic properties ( Sheng et al, 2022 ). As the core group of CHM for cancer patients, Hedyotis diffusa Willd.…”

Hedyotis diffusa–Sculellaria barbata (HD–SB) suppresses the progression of colorectal cancer cells via the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis

“…Scutellaria barbata (SB) belongs to the Labiatae family, which has improved cellular immune function and anticancer effects and is widely applied to treat various tumors 18 . A previous study demonstrated that SB extract inhibited tumor growth of prostate cancer via PI3K/Akt pathway 19 . HD–SB in compatibility with TCM is applied in clinical cancer treatment in the form of couplet medicine.…”