PMID- 32277664 OWN - NLM STAT- MEDLINE DCOM- 20201209 LR - 20210908 IS - 2241-6293 (Electronic) IS - 1107-0625 (Linking) VI - 25 IP - 1 DP - 2020 Jan-Feb TI - The anticancer effects of 7-Methoxyheptaphylline against the human retinoblastoma cells are facilitated via S-phase cell cycle arrest, mitochondrial apoptosis and inhibition of Wnt/beta-catenin signalling pathway. PG - 421-426 AB - PURPOSE: The main purpose of the current study was to evaluate the anticancer action of 7-Methoxyheptaphylline in Y-79 human retinoblastoma cells along with evaluating its effects on cellular apoptosis, cell cycle phase distribution and Wnt/beta-catenin signalling pathway. METHODS: The retinoblastoma cell line RbY-79 was used in this study. Cell viability was assessed by WTS-1 assay while apoptotic studies were carried out by DAPI, acridine orange (AO)/ethidium bromide (EB), annexin V + propidium iodide (PI) staining using fluorescence microscopy and flow cytometry. Effects on cell cycle progression were studied using Annexin V/PI staining in combination with flow cytometry. Western blot assay was used to examine the effects on Bax, Bcl-2 and proteins associated with Wnt/beta-catenin signalling pathway. RESULTS: The results indicated that 7-Methoxyheptaphylline suppressed the viability of the Y-79 cells concentration-dependently with IC50 value of 15.5 muM. The percentage of the DAPI-positive cells showed a significant upsurge reminiscent of the apoptosis in the Y-79 retinoblastoma cells. 7-Methoxyheptaphylline also caused considerable nuclear fragmentation of the Y-79 retinoblastoma cells, representative of apoptosis. The apoptosis percentage increased significantly as the dose of the 7-Methoxyheptaphylline increased from 0 to 12, 24 and 48 microM. The molecule caused upregulation of Bax and downregulation of Bcl-2 in Y-79 retinoblastoma cells. 7-Methoxyheptaphylline also caused S-phase cell cycle arrest with concomitant concentration-dependent decline in the expression levels of cyclin A, E and D1. It was also seen that increasing doses of 7-Methoxyheptaphylline led to a dose-dependent decline in the expression levels of wnt-13a and beta-catenin. CONCLUSIONS: In conclusion, it is believed that the molecule may prove to be a promising anticancer agent for the treatment of retinoblastoma. FAU - Chen, Bin AU - Chen B AD - Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China, 430060. FAU - He, Tao AU - He T FAU - Wu, Li AU - Wu L FAU - Cao, Ting AU - Cao T FAU - Zheng, Hongmei AU - Zheng H LA - eng PT - Journal Article PL - Cyprus TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - 0 (7-methoxyheptaphylline) RN - 0 (Carbazoles) SB - IM ECI - J BUON. 2021 May-Jun;26(3):1182. PMID: 34268999 MH - Apoptosis/*drug effects MH - Carbazoles/pharmacology/*therapeutic use MH - Cell Cycle Checkpoints/*drug effects MH - Humans MH - Mitochondria/*drug effects MH - Retinoblastoma/*drug therapy/pathology MH - S Phase/*drug effects MH - Wnt Signaling Pathway/*drug effects EDAT- 2020/04/12 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/04/12 06:00 PHST- 2020/04/12 06:00 [entrez] PHST- 2020/04/12 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PST - ppublish SO - J BUON. 2020 Jan-Feb;25(1):421-426.