PMID- 33627540 OWN - NLM STAT- MEDLINE DCOM- 20210727 LR - 20211204 IS - 1347-5223 (Electronic) IS - 0009-2363 (Linking) VI - 69 IP - 5 DP - 2021 May 1 TI - Arctigenin Triggers Apoptosis and Autophagy via PI3K/Akt/mTOR Inhibition in PC-3M Cells. PG - 472-480 LID - 10.1248/cpb.c21-00021 [doi] AB - Arctigenin (ARG), a natural lignans compound isolated from Arctium lappa L. In this study, the anti-tumor effect of ARG on prostate cancer cell PC-3M and the mechanism of apoptosis and autophagy induced by phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were discussed, and further confirmed by the joint treatment of ARG and PI3K inhibitor LY294002. Here, the effect of ARG on cell viability was evaluated in PC-3M cells by Cell Counting Kit-8 reagent (CCK-8) assay. After the treatment of ARG, colony formation assay was used to detect the anti-proliferation effect. Annexin V-fluoresceine isothiocyanate/propidium iodide (FITC/PI) kit and 4',6-diamidino-2-phenylindole (DAPI) staining were used to detect the apoptosis level, and cell cycle changes were analyzed by flow cytometry. The expression of autophagy was detected by acridine orange staining. In addition, the expression levels of apoptosis and autophagy-related proteins were analyzed by Western blot. The result showed that different concentrations of ARG inhibited the proliferation of PC-3M cells. DAPI staining and flow cytometry showed that ARG induced PC-3M cell apoptosis and arrested cell in G0/G1 phase. Acridine orange staining showed that ARG induced autophagy in PC-3M cells. Western blot experiments showed that ARG inhibited the expression of Bcl-2, promoted the expression of Bax and cleaved caspase-3. At the same time, the expression of autophagy-related proteins LC3B-II and Beclin-1 increased after ARG treatment, but P62 decreased. In addition, further studies have shown that treatment with LY294002 enhanced the effects of ARG on the expression of proteins associated with apoptosis and autophagy, indicating that ARG may induce apoptosis and autophagy through PI3K/Akt/mTOR pathway. FAU - Sun, Bai-Ling AU - Sun BL AD - College of Chinese Medicinal Material, Jilin Agricultural University. FAU - Cai, En-Bo AU - Cai EB AD - College of Chinese Medicinal Material, Jilin Agricultural University. FAU - Zhao, Yan AU - Zhao Y AD - College of Chinese Medicinal Material, Jilin Agricultural University. FAU - Wang, Yu AU - Wang Y AD - College of Chinese Medicinal Material, Jilin Agricultural University. FAU - Yang, Li-Min AU - Yang LM AD - College of Chinese Medicinal Material, Jilin Agricultural University. FAU - Wang, Jing-Yao AU - Wang JY AD - College of Chinese Medicinal Material, Jilin Agricultural University. LA - eng PT - Journal Article DEP - 20210225 PL - Japan TA - Chem Pharm Bull (Tokyo) JT - Chemical & pharmaceutical bulletin JID - 0377775 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Furans) RN - 0 (Lignans) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - U76MR9VS6M (arctigenin) SB - IM MH - Antineoplastic Agents, Phytogenic/chemistry/isolation & purification/*pharmacology MH - Apoptosis/*drug effects MH - Arctium/chemistry MH - Autophagy/*drug effects MH - Cell Proliferation/drug effects MH - Dose-Response Relationship, Drug MH - Drug Screening Assays, Antitumor MH - Furans/chemistry/isolation & purification/*pharmacology MH - Humans MH - Lignans/chemistry/isolation & purification/*pharmacology MH - Molecular Conformation MH - Phosphatidylinositol 3-Kinase/metabolism MH - Protein Kinase Inhibitors/chemistry/isolation & purification/*pharmacology MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism MH - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism MH - Tumor Cells, Cultured OTO - NOTNLM OT - PC-3M OT - apoptosis OT - arctigenin OT - autophagy EDAT- 2021/02/26 06:00 MHDA- 2021/07/28 06:00 CRDT- 2021/02/25 05:35 PHST- 2021/02/26 06:00 [pubmed] PHST- 2021/07/28 06:00 [medline] PHST- 2021/02/25 05:35 [entrez] AID - 10.1248/cpb.c21-00021 [doi] PST - ppublish SO - Chem Pharm Bull (Tokyo). 2021 May 1;69(5):472-480. doi: 10.1248/cpb.c21-00021. Epub 2021 Feb 25.