PMID- 37859622 OWN - NLM STAT- MEDLINE DCOM- 20231113 LR - 20231113 IS - 1791-2431 (Electronic) IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 50 IP - 6 DP - 2023 Dec TI - Licochalcone A induces cell cycle arrest and apoptosis via suppressing MAPK signaling pathway and the expression of FBXO5 in lung squamous cell cancer. LID - 214 [pii] LID - 10.3892/or.2023.8651 [doi] AB - Lung squamous cell carcinoma (LSCC) is a highly heterogeneous malignancy with high mortality and few therapeutic options. Licochalcone A (LCA, PubChem ID: 5318998) is a chalcone extracted from licorice and possesses anticancer and anti‑inflammatory activities. The present study aimed to elucidate the anticancer effect of LCA on LSCC and explore the conceivable molecular mechanism. MTT assay revealed that LCA significantly inhibited the proliferation of LSCC cells with less cytotoxicity towards human bronchial epithelial cells. 5‑ethynyl‑2'‑deoxyuridine (EdU) assay demonstrated that LCA could reduce the proliferation rate of LSCC cells. The flow cytometric assays indicated that LCA increased the cell number of the G1 phase and induced the apoptosis of LSCC cells. LCA downregulated the protein expression of cyclin D1, cyclin E, CDK2 and CDK4. Meanwhile, LCA increased the expression level of Bax, cleaved poly(ADP‑ribose)polymerase‑1 (PARP1) and caspase 3, as well as downregulated the level of Bcl‑2. Proteomics assay demonstrated that LCA exerted its antitumor effects via inhibiting mitogen‑activated protein kinase (MAPK) signaling pathways and the expression of F‑box protein 5 (FBXO5). Western blot analysis showed that LCA decreased the expression of p‑ERK1/2, p‑p38MAPK and FBXO5. In the xenograft tumors of LSCC, LCA significantly inhibited the volumes and weight of tumors in nude mice with little toxicity in vital organs. Therefore, the present study demonstrated that LCA effectively inhibited cell proliferation and induced apoptosis in vitro, and suppressed xenograft tumor growth in vivo. LCA may serve as a future therapeutic candidate of LSCC. FAU - Fan, Xiaoli AU - Fan X AD - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China. FAU - Guan, Guoqiang AU - Guan G AD - College of Pharmacy, Guilin Medical University, Guilin, Guangxi 541199, P.R. China. FAU - Wang, Juan AU - Wang J AD - College of Pharmacy, Guilin Medical University, Guilin, Guangxi 541199, P.R. China. FAU - Jin, Meihua AU - Jin M AD - Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China. FAU - Wang, Liming AU - Wang L AD - Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China. FAU - Duan, Xiaoqun AU - Duan X AD - Industrial Technology Research Institute of Pharmacy, Guilin Medical University, Guilin, Guangxi 541199, P.R. China. LA - eng PT - Journal Article DEP - 20231020 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Cell Cycle Proteins) RN - 0 (Chalcones) RN - 0 (F-Box Proteins) RN - 0 (FBXO5 protein, human) RN - JTV5467968 (licochalcone A) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Humans MH - Mice MH - Apoptosis MH - *Carcinoma, Squamous Cell/drug therapy/genetics/metabolism MH - Cell Cycle Checkpoints/drug effects/genetics MH - Cell Cycle Proteins/metabolism MH - Cell Line, Tumor MH - Cell Proliferation MH - *Chalcones/pharmacology/therapeutic use MH - *F-Box Proteins/metabolism MH - Lung/pathology MH - Mice, Nude MH - Mitogen-Activated Protein Kinases/metabolism MH - Signal Transduction MH - *Lung Neoplasms/drug therapy/genetics/metabolism PMC - PMC10620845 OTO - NOTNLM OT - F‑box protein 5 OT - apoptosis OT - licochalcone A OT - lung squamous cell carcinoma OT - proteomics COIS- The authors declare that they have no competing interests. EDAT- 2023/10/20 06:42 MHDA- 2023/10/23 01:18 PMCR- 2023/10/20 CRDT- 2023/10/20 04:15 PHST- 2023/06/13 00:00 [received] PHST- 2023/10/02 00:00 [accepted] PHST- 2023/10/23 01:18 [medline] PHST- 2023/10/20 06:42 [pubmed] PHST- 2023/10/20 04:15 [entrez] PHST- 2023/10/20 00:00 [pmc-release] AID - 214 [pii] AID - OR-50-6-08651 [pii] AID - 10.3892/or.2023.8651 [doi] PST - ppublish SO - Oncol Rep. 2023 Dec;50(6):214. doi: 10.3892/or.2023.8651. Epub 2023 Oct 20.