Skullcapflavone I suppresses proliferation of human lung cancer cells via down-regulating microRNA-21.
BACKGROUND
Lung cancer is the most leading cause of cancer-related deaths worldwide. Skullcapflavone I is a flavone compound extracted from Scutellaria baicalensis Georgi (Wogon). The present study investigated the effects of skullcapflavone I on human lung cancer cell proliferation, as well as underlying possible mechanism.


METHODS
Cell proliferation was detected using Trypan blue assay. Cell viability was measured using cell counting kit 8 (CCK-8) assay. Quantitative reverse transcription PCR (qRT-PCR) was performed to assess microRNA-21 (miR-21) expression. Cell transfection was conducted to enhance the levels of miR-21 and protein phosphatase 2A (PP2A). Western blotting was used to evaluate the expressions of proliferation cell nuclear antigen (PCNA), Cyclin D1, PP2A, phosphatidylinositol 3-kinase (PI3K), protein kinase 3 (AKT), mechanistic target of rapamycin (mTOR) and p70S6K.


RESULTS
Skullcapflavone I significantly suppressed the viability and proliferation of A549 and H1975 cells. The expressions of miR-21 in A549 and H1975 cells were drastically decreased after skullcapflavone I treatment. Overexpression of miR-21 remarkably reversed the skullcapflavone I-induced A549 cell viability inhibition. Moreover, skullcapflavone I enhanced the expression of PP2A in A549 cells. Skullcapflavone I inactivated PI3K/AKT/mTOR signaling pathway in A549 cells via up-regulating PP2A. Besides, skullcapflavone I treatment had no significant influence on human normal bronchial epithelial 16HBE cell viability, proliferation and apoptosis.


CONCLUSION
Skullcapflavone I exerted anti-cancer effect on lung cancer cells by down-regulating miR-21 expression, up-regulating PP2A expression and then inactivating PI3K/AKT/mTOR signaling pathway.
['Yang|Yadong|Y|', 'An|Ran|R|', 'Feng|Tao|T|', 'Qin|Xiaofeng|X|', 'Zhang|Jian|J|', 'Bo|Youling|Y|', 'Niu|Ben|B|']
D000072283:A549 Cells D002460:Cell Line D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D015536:Down-Regulation D047309:Flavones D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008175:Lung Neoplasms D035683:MicroRNAs D019869:Phosphatidylinositol 3-Kinases D054648:Protein Phosphatase 2 D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction D058570:TOR Serine-Threonine Kinases
Skullcapflavone I Lung cancer MicroRNA-21 Protein phosphatase 2A PI3K/AKT/mTOR signaling pathway