Oncogene 30, 366–371. 2011;59(20):10934–10942. Cell Dev. Both compounds can inhibit the proliferation, migration, adhesion and invasive properties of tumor cells, and induce tumor cell cycle arrest (Chao et al., 2007; Chiu et al., 2011; Takahashi et al., 2011; Aryal et al., 2014; Wang et al., 2015; Gong et al., 2017). Wang CZ, Zhang CF, Chen L, Anderson S, Lu F, Yuan CS. Health Benefits of Baicalein A., Bassett, R. L. Jr., Ng, C. S., Curry, J. L., Joseph, R. W., Alvarado, G. C., et al. Res. Pharmacol. Cancer. (2017). Brose, M. S., Volpe, P., Feldman, M., Kumar, M., Rishi, I., Gerrero, R., et al. Cancer Res. 109, 3012–3043. Chinese Skullcap and the Baicalein Within It Inhibit the Replication of SARS-CoV-2 A crude ethanol extract of Chinese Skullcap inhibited the 3CL protease, also known as the “main protease,” of SARS-CoV-2, the coronavirus that causes COVID-19. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Baicalin is a flavone found in several species in the genus Scutellaria, including Scutellarialateriflora (blue skullcap). The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. The cell growth was evaluated at different time points using the cell number counting (A), and cell proliferation was determined using [3H]-thymidine assays (B). 287, 41797–41807. We then further confirmed whether baicalein and baicalin-mediated inhibition of tumor growth in vivo is due to suppression of glucose metabolism in tumor cells. It is the aglycone of baicalin. doi: 10.1016/j.bbabio.2015.06.016, Keywords: baicalein, baicalin, melanoma, N-RAS, B-RAF, apoptosis, senescence, glucose metabolism, Citation: Huang L, Peng B, Nayak Y, Wang C, Si F, Liu X, Dou J, Xu H and Peng G (2020) Baicalein and Baicalin Promote Melanoma Apoptosis and Senescence via Metabolic Inhibition. Data shown in different melanoma cells are mean ± SD from three independent experiments. Adherent cells were counted and averaged in 10 fields at high (×400) magnification with a microscope. 1996;24(1):31–36. The present study demonstrated that the Scutellariae radix compounds baicalein and baicalin may serve as drugs for the treatment of autoimmune diseases, including rheumatoid arthritis and inflammatory bowel disease. 1) Anxiety Baicalein and baicalin inhibit the action potential of the neurons that raise anxiety. In addition, melanoma with N-RAS and B-RAF mutations has been well-recognized as a challenge that brings out more difficulties for the treatment (Brose et al., 2002; Omholt et al., 2003; Thumar et al., 2014). Thomas, N. E., Edmiston, S. N., Alexander, A., Groben, P. A., Parrish, E., Kricker, A., et al. Baicalin treatment inhibits the increased expression of the proinflammatory cytokines TLR2/4, MyD88, p-NF-κB, and p- IκB, as well as increase the expression of IκB protein, an NF-κB inhibitor, with the degree of inhibition positively related to the dosage of Baicalin. All the results from both in vivo and in vitro studies indicate that baicalein and baicalin can rewrite tumor metabolism and have potent anti-tumor effects in melanoma. Int J Oncol. The expression levels of each gene were normalized to β-actin expression levels and adjusted to the levels in untreated tumor cells (medium). We then confirmed the functional importance of mTOR-HIFα signaling pathway in glucose metabolism suppression and senescence induction in melanoma cells mediated by baicalein and baicalin. Both human and mouse melanoma cells pretreated with the indicated concentrations of baicalein and baicalin were cultured in the fibronectin-coated plates for 45 min. We observed that culture with baicalein and baicalin in human Mel586, SK-MEL-2, and A375 melanoma cells as well as mouse B16F0 melanoma cells significantly increased the numbers of SA-β-Gal+ cells, indicating the induction of tumor cell senescence (Figures 4A,B). We observed that baicalein and baicalin treatments markedly suppressed tumor cell proliferation as indicated by a decrease of Ki-67+ cell populations in tumor tissues (Figures 8D,E). Pharmacol. In fact, many promising drugs have been developed based on the natural products and applied in clinical trials for various disease treatments including cancers (Cragg et al., 2009; Cragg and Newman, 2013; Stover et al., 2014). (A) Both baicalein and baicalin dramatically inhibited B16F0 melanoma tumor growth in NSG immunodeficient mice. Baicalin, but not baicalein, significantly…, Figure 5. Figure 4. The plant is found in Japan, China, Korea, Mongolia, and Russia 1 and thrives on … Results shown in the histogram (B) are summaries of mean ± SD from three independent experiments. Melanoma cells were transfected with pCDNA-Glut1 or control vector plasmids for 24 h, then cultured for 3 days in the presence of baicalein or baicalin (40 μM for Mel586, A375, and SK-mel-2 cells, and 50 μM for B16F0 cells). Hyperactivation of MEK-ERK1/2 signaling and resistance to apoptosis induced by the oncogenic B-RAF inhibitor, PLX4720, in mutant N-RAS melanoma cells. While plasma contained predominantly conjugates of baicalein, wogonin, and oroxylin A, both aglycones and conjugates were found in all other tissues investigated and in tumor. 255, 316–326. Baicalein and baicalin are active components of Scutellaria baicalensis Georgi. Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling. doi: 10.1016/j.phrs.2015.08.021, Ding, Y., Dou, J., Teng, Z., Yu, J., Wang, T., Lu, N., et al. In our current studies, we utilized different types of melanoma cell lines with/without N-RAS and B-RAF mutations, including Mel586, SK-MEL-2 (wild type B-Raf and mutant N-RAS), A375 (B-RAF V600E and wild type N-RAS), as well as mouse B16F0 melanoma cell line. In addition, we demonstrated that baicalein and baicalin can suppress tumorigenesis and tumor growth in vivo in the melanoma model. Baicalein and baicalin strongly inhibit melanoma cell behaviors and functions, including tumor cell growth and proliferation, as well as colony formation and migration. Clin. We show here that low micromolar concentrations of baicalein, and especially its oxidized forms, inhibit the formation of alpha-synuclein fibrils. 62, 6997–7000. However, unlike the effect in colon cancer cells, treatment with baicalein induced more senescent cell populations in both human and mouse melanoma cell lines than that of baicalin treatment in those melanoma cells (Figures 4A,B). We further determined whether baicalein and baicalin can inhibit tumor growth of melanoma cells. Am J Chin Med. doi: 10.1074/jbc.m112.390906, Kaplan, F. M., Shao, Y., Mayberry, M. M., and Aplin, A. E. (2011). Acta 1847, 1254–1266. Nature 464, 431–435. (2010). Cell preparation and treatment were identical to panel (A). Melanoma cells were transfected with Retro-Rheb plasmid or pretreated with DMOG (0.1 mM) for 24 h, then cultured for 3 days in the presence of 40 μM of baicalein or baicalin. Nat. We will continue our future studies to explore the possibility that combining baicalein or baicalin treatment with other therapeutic strategies including immunotherapy will synergistically enhance anti-tumor efficacy in different melanoma models. Cancer Facts and Figures 2018. (2015). Oncol. Stained cells were analyzed on a FACSCalibur (BD Bioscience) and the data were analyzed with the FlowJo software (Tree Star, Ashland, OR, United States). Scutellaria baicalensis georgi; apoptosis; baicalein; baicalin; colon cancer. The study aimed to establish an UPLC-MS/MS method for the determination of baicalin in rat plasma,in order to study the effect of PEG400 on pharmacokinetics of baicalin and baicalein in normal and gut microbiotadysbiosis rats. 6:122. doi: 10.3389/fcell.2018.00122, Stover, J. F., Belli, A., Boret, H., Bulters, D., Sahuquillo, J., Schmutzhard, E., et al. Metabolic reprogramming of immune cells in cancer progression. We have recently demonstrated that baicalein and baicalin could inhibit human colon cancer cell growth and proliferation in vitro and in vivo (Dou et al., 2018; Wang et al., 2018). In addition, existing fibrils of alpha-synuclein are disaggregated by baicalein. Wang, Z., Ma, L., Su, M., Zhou, Y., Mao, K., Li, C., et al. With a high rate of death every year Peng, Nayak, Wang,,. And Scutellaria lateriflora especially melanoma with mutations is needed Koppenol, W. C. and. Converted from baicalin cancer: Focusing on traditional Chinese herb flavonoid, originally isolated from the roots the... Skin cancer, is one of baicalein and baicalin PI3K/Akt pathway epithelial cells chronic gastritis, peptic ulcers, and growth... Shoc2 and CRAF mediate ERK1/2 reactivation in mutant N-RAS melanoma cells after with. 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