PMID- 35321703 OWN - NLM STAT- MEDLINE DCOM- 20220325 LR - 20220329 IS - 2662-7671 (Electronic) IS - 2662-7671 (Linking) VI - 22 IP - 1 DP - 2022 Mar 23 TI - Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway. PG - 85 LID - 10.1186/s12906-022-03568-3 [doi] LID - 85 AB - BACKGROUND: The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: In vitro cultured cells were treated with ILTPs; the proliferation of A549 cells and BEAS-2B human normal lung epithelial cells (Beas-2B cells) was observed using the 3-(4,5-dimethylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the survival status of A549 cells was observed by fluorescence staining. The expression of A549 cells was observed by quantitative polymerase chain reaction (qPCR) assay and Western blot analysis, while the compound composition of ILTPs was detected using high-performance liquid chromatography (HPLC). RESULTS: The experimental results showed that the proliferation of Beas-2B cells was unaffected by treatment with 0-500 mug/mL of ILTPs, whereas the decreased proliferation of A549 cells was observed with the increasing concentrations of ILTPs. Additionally, ILTPs elevated the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) and promoted apoptosis in A549 cells. The results of qPCR experiments showed that ILTPs upregulated caspase-9 mRNA expression and downregulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma-2 (Bcl-2), nuclear factor-kappaB (NF-kappaB), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1alpha), and cyclooxygenase-2 (COX-2) expression in A549 cells. The Western blot analysis results also showed that ILTPs could reduce the protein expression of PI3K and Akt. The HPLC results showed that the main compounds present in the ILTPs were rutin, kaempferol, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C. CONCLUSIONS: Thus, this study indicated that the polyphenols of I. latifolia act as a class of natural functional food materials that potently suppress cancer by exerting their inhibitory effects on A549 cell proliferation through five key polyphenolic compounds. CI - (c) 2022. The Author(s). FAU - Chen, Jing AU - Chen J AD - Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China. FAU - Du, Yesheng AU - Du Y AD - Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China. FAU - Long, Yanyan AU - Long Y AD - Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China. FAU - Tao, Dan AU - Tao D AD - Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China. FAU - Hu, Mengyu AU - Hu M AD - Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, China. FAU - Jiang, Yong AU - Jiang Y AD - Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, China. FAU - Wan, Yue AU - Wan Y AD - Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, China. FAU - Yang, Dingyi AU - Yang D AD - Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China. cqres@foxmail.com. LA - eng PT - Journal Article DEP - 20220323 PL - England TA - BMC Complement Med Ther JT - BMC complementary medicine and therapies JID - 101761232 RN - 0 (Polyphenols) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - A549 Cells MH - Humans MH - *Ilex/metabolism MH - *Lung Neoplasms/genetics MH - Phosphatidylinositol 3-Kinase/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Polyphenols/pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction MH - Vascular Endothelial Growth Factor A PMC - PMC8943935 OTO - NOTNLM OT - Ilex latifolia Thunb OT - Lung cancer OT - MTT OT - PI3K-Akt signaling pathway OT - Polyphenols COIS- The authors declare that they have no competing interests. EDAT- 2022/03/25 06:00 MHDA- 2022/03/26 06:00 PMCR- 2022/03/23 CRDT- 2022/03/24 05:30 PHST- 2021/10/31 00:00 [received] PHST- 2022/03/11 00:00 [accepted] PHST- 2022/03/24 05:30 [entrez] PHST- 2022/03/25 06:00 [pubmed] PHST- 2022/03/26 06:00 [medline] PHST- 2022/03/23 00:00 [pmc-release] AID - 10.1186/s12906-022-03568-3 [pii] AID - 3568 [pii] AID - 10.1186/s12906-022-03568-3 [doi] PST - epublish SO - BMC Complement Med Ther. 2022 Mar 23;22(1):85. doi: 10.1186/s12906-022-03568-3.