Baicalin, the major component of traditional Chinese medicine Scutellaria baicalensis induces colon cancer cell apoptosis through inhibition of oncomiRNAs

Abstract

Colorectal cancer (CRC) is among the most frequently occurring cancers worldwide. Baicalin is isolated from the roots of Scutellaria baicalensis and is its dominant flavonoid. Anticancer activity of baicalin has been evaluated in different types of cancers, especially in CRC. However, the molecular mechanisms underlying the contribution of baicalin to the treatment of CRC are still unknown. Here, we confirmed that baicalin can effectively induce and enhance apoptosis in HT-29 cells in a dose-dependent manner and suppress tumour growth in xenografted nude mice. We further performed a miRNA microarray analysis of baicalin-treated and untreated HT-29 cells. The results showed that a large number of oncomiRs, including miR-10a, miR-23a, miR-30c, miR-31, miR-151a and miR-205, were significantly suppressed in baicalin-treated HT-29 cells. Furthermore, our in vitro and in vivo studies showed that baicalin suppressed oncomiRs by reducing the expression of c-Myc. Taken together, our study shows a novel mechanism for anti-cancer action of baicalin, that it induces apoptosis in colon cancer cells and suppresses tumour growth by reducing the expression of c-Myc and oncomiRs.

Scutellaria baicalensis Georgi. (Lamiaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology

“…In addition to the above chemical compositions, there are some other ingredients that have been isolated and identified from Scutellaria baicalensis including b-sitosterol (64), [29] benzoic acid (65) [30] and benzyl alcohol (66). [31] Furthermore, Tuan et al (2014) found that the main carotenoids in Scutellaria baicalensis were lutein (67) and b-carotene (68), and the leaves contained a lot of carotene.…”

“…[64] In addition to these, Lin et al (2013) revealed that the EESB and its active flavonoids could reversibly inhibit myeloma SP cells, and they also discovered a potential new molecular mechanism possibly associated with the target SP cells by modulating the expression of the ABCG2 protein. [65] Recently, Tao et al [66] indicated that baicalin, the main component of Chinese medicine Scutellaria baicalensis, could significantly induce and enhance apoptosis of HT-29 colon cancer cells in a dose-and time-dependent manner, and strongly inhibit tumour growth in xenograft nude mice. [66] Their study confirmed that baicalin induced apoptosis in colon cancer cells through a mechanism possibly associated with the inhibition of c-Myc expression and downregulation of oncomiRs associated with many apoptoses.…”

“…[65] Recently, Tao et al [66] indicated that baicalin, the main component of Chinese medicine Scutellaria baicalensis, could significantly induce and enhance apoptosis of HT-29 colon cancer cells in a dose-and time-dependent manner, and strongly inhibit tumour growth in xenograft nude mice. [66] Their study confirmed that baicalin induced apoptosis in colon cancer cells through a mechanism possibly associated with the inhibition of c-Myc expression and downregulation of oncomiRs associated with many apoptoses.…”

“…Fei et al [59] used the newly developed vitro pathway array technology to determine that the WESB exhibited a 50% strong growth inhibition concentration on HepG2 cells through G2/M phase arrest with the IC 50 value of 360 lg/ml. [59] Additionally, it was reported that the EESB, at a dose of 200 mg/kg, had a potential protective effect on LPS- Table 3 Other chemical compounds isolated from Scutellaria baicalensis (64)(65)(66)(67)(68)(69)(70)(71) No. Name…”

Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals

“…Apoptotic cell death is induced by baicalin treatments, and further evidence showed that various oncogenic miRNAs, such as miR-23 and miR-217, can be depleted by baicalin in colorectal cancer [ 36 , 99 ] ( Figure 2 and Table 3 ). Baicalin impedes the growth of colorectal cancer in vivo via repressing c-Myc expression in conjunction with a reduction of miR-23, which is one of the c-Myc-regulated miRNAs [ 36 ]. Additionally, baicalin can induce apoptosis through subduing Wnt/β-catenin signaling, accompanied by the upregulated levels of Dickkopf-related protein 1 (DKK1), an endogenous inhibitor of Wnt signaling [ 99 ].…”