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

Published: 27 September 2018 Yili Tao, Shoubin Zhan, Yanbo Wang, Geyu Zhou, Hongwei Liang, Xi Chen & Hong Shen Scientific Reportsvolume 8, Article number: 14477 (2018) | Download Citation 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. Introduction Colorectal cancer (CRC) is one of the most common cancers worldwide1. In the United States, it was estimated that there were 132,700 newly diagnosed CRC cases as well as 49,700 CRC-related deaths in 20152, which underscores the need to develop more efficient or complementary treatment3,4. Herbal medication is an approach that is gaining big attention for CRC treatment nowadays2,5, while botanicals are known to be an important resource for several efficacious chemotherapy agents6,7. Thus, identifying non-toxic natural ingredients from herbs is a crucial step in promoting CRC therapeutics8,9. Natural products have recently received attention for the discovery of novel anticancer therapeutic agents as they have long been used as alternative remedies for a variety of diseases, including cancer, with relatively fewer side effects10,11. Therefore, identifying natural ingredients to advance anticancer treatment is in prospect. Baicalin (5, 6-dihydroxy-7-O-glucuronide flavone) is a predominant flavonoid isolated from the roots of Scutellaria baicalensis Georgi (Huang Qin) with a defined chemical constitution12,13 and various pharmacological activities, including anti-oxidative, anti-viral, anti-inflammatory, anti-HIV and anti-proliferative activities14,15,16,17,18. It also has beneficial effects in the treatment of several cancers, including CRC5. However, the molecular mechanisms underlying the contribution of baicalin to CRC treatment remain elusive. MicroRNAs (miRNAs) are a class of 18–22 nucleotides small non-coding RNA molecules that play pivotal roles in development, differentiation, apoptosis, senescence and cell proliferation through post-transcriptional regulation of gene expression19. Aberrant expression of miRNAs is known to be associated with a variety of human diseases, such as cardiac disorders, immune-related disorders, neurodegenerative diseases and cancers20,21, including CRC22. Many oncogenic miRNAs (oncomiRs) that mediate cell growth and tumour progression, including miR-21, miR-23a, miR-17–5p, miR-15b, miR-181b, miR-191 and miR-200c, are upregulated in CRC23,24,25,26, while others, such as miR-204, miR-34a and miR-126, are found to be downregulated and may function as tumour suppressors27,28,29. The deregulation of various miRNAs is related to tumour diagnosis and prognosis, illustrating that they might provide important references for clinical applications30,31,32. In the present study, we attempt to demonstrate whether and how baicalin contributes to CRC management. We first confirmed that baicalin effectively enhances apoptosis in HT-29 cells in a dose and time-dependent manner and suppresses tumour growth in xenografted nude mice. Using a miRNA microarray analysis, we further showed that the enhancement of apoptosis is coupled with downregulation of a large number of oncomiRs, including miR-10a, miR-23a, miR-30c, miR-31, miR-151a and miR-205, after baicalin treatment. Finally, we demonstrated the role of c-Myc, which is also suppressed after baicalin treatment, in regulating these oncomiRs both in vitro and in vivo.