Antitumor effect of baicalin from the Scutellaria baicalensis radix extract in B-acute lymphoblastic leukemia with different chromosomal rearrangements

• Published in: International immunopharmacology 2020-02, Vol.79, p.106114-106114, Article 106114
• Main Authors: Orzechowska, Beata U., Wróbel, Grażyna, Turlej, Eliza, Jatczak, Bogna, Sochocka, Marta, Chaber, Radosław
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Anticancer properties; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Apoptosis - drug effects; B-acute lymphoblastic leukemia; B-Lymphocytes - pathology; Baicalin; Biotechnology; Bone marrow; Caspase-3; Cell cycle; Cell Cycle Checkpoints; Cell death; Cell Line, Tumor; Cell proliferation; Chemical compounds; Children; Chromosomal rearrangements; Chromosome Aberrations; Chromosome rearrangements; Chromosome translocations; Cyclin dependent kinase inhibitor p27Kip1; Cyclin-dependent kinase inhibitor p27; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Enzyme inhibitors; Flavonoids; Flavonoids - therapeutic use; G1 phase; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 - metabolism; Glycogens; Humans; Kinases; Leukemia; Lymphatic leukemia; Malignancy; Mode of action; Myeloid-Lymphoid Leukemia Protein - genetics; PBX1 gene; Pharmacology; Phosphorylation; Plant Extracts - pharmacology; Pre-B-Cell Leukemia Transcription Factor 1 - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Scutellaria baicalensis; Scutellaria baicalensis Georgi; Transcription factors
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.106114

[Display omitted] •Baicalin exhibits potent anti-cancer activities against B-cell acute lymphocytic leukemia.•Baicalin reduces proliferation of cell lines and activates the intrinsic apoptotic pathway.•Baicalin inhibits the glycogen synthase kinase 3β and induces cell cycle arrest through the up-regulation of p27Kip1.•Chromosomal translocations in leukemic cell lines impact the response to baicalin treatment.•The most sensitive to baicalin were cell lines with MLL and PBX1 gene rearrangements. Acute B-lymphoblastic leukemia (B-ALL) is the most common hematologic malignancy in children. Many cases of B-ALL harbor chromosomal translocations which are often critical determinants of prognosis. Most of them represent altered transcription factors that impact gene transcription or enhance signaling. B-ALLs harboring the mixed-lineage leukemia 1 (MLL1) gene rearrangements represent aggressive, high-risk type of early childhood leukemias that are usually associated with a very poor prognosis. Therefore, there is an urgent need for novel therapeutic agents as well as new treatment strategies. The objective was to examine the vitro inhibitory effects of Scutellaria baicalensis root extract (SBE) in B-ALL cell lines with different chromosomal rearrangements and in leukemic blasts derived from patients’ bone marrow (BMCs). In this study we showed that baicalin which is the main component of the SBE possess antitumor activity against all leukemic cell lines especially those with MLL and PBX1 gene rearrangements. Baicalin inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced cell death through caspase 3/7 activation. Moreover, baicalin treatment inhibited the glycogen synthase kinase-3β (GSK‐3β) by suppressing its phosphorylation at Y216, and upregulated the downstream mediator of the cell cycle arrest - cyclin dependent kinase inhibitor p27Kip1. Bone marrow derived blasts from B-ALL patients also exhibited varied sensitivity towards baicalin with 72% patients sensitive to the SBE and baicalin treatment. Taken together, our findings provide new insights into the anti-cancer properties of baicalin by showing its diverse mode of action which might be related to the different genetic background.