PMID- 36230603 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221017 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 14 IP - 19 DP - 2022 Sep 26 TI - Plant-Derived Sulforaphane Suppresses Growth and Proliferation of Drug-Sensitive and Drug-Resistant Bladder Cancer Cell Lines In Vitro. LID - 10.3390/cancers14194682 [doi] LID - 4682 AB - Combined cisplatin-gemcitabine (GC) application is standard for treating muscle-invasive bladder cancer. However, since rapid resistance to treatment often develops, many patients turn to supplements in the form of plant-based compounds. Sulforaphane (SFN), derived from cruciferous vegetables, is one such compound, and the present study was designed to investigate its influence on growth and proliferation in a panel of drug-sensitive bladder cancer cell lines, as well as their gemcitabine- and cisplatin-resistant counterparts. Chemo-sensitive and -resistant RT4, RT112, T24, and TCCSUP cell lines were exposed to SFN in different concentrations, and tumor growth, proliferation, and clone formation were evaluated, in addition to apoptosis and cell cycle progression. Means of action were investigated by assaying cell-cycle-regulating proteins and the mechanistic target of rapamycin (mTOR)/AKT signaling cascade. SFN significantly inhibited growth, proliferation, and clone formation in all four tumor cell lines. Cells were arrested in the G2/M and/or S phase, and alteration of the CDK-cyclin axis was closely associated with cell growth inhibition. The AKT/mTOR signaling pathway was deactivated in three of the cell lines. Acetylation of histone H3 was up-regulated. SFN, therefore, does exert tumor-suppressive properties in cisplatin- and gemcitabine-resistant bladder cancer cells and could be beneficial in optimizing bladder cancer therapy. FAU - Xie, Hui AU - Xie H AUID- ORCID: 0000-0002-6219-1696 AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. AD - Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany. FAU - Rutz, Jochen AU - Rutz J AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. FAU - Maxeiner, Sebastian AU - Maxeiner S AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. FAU - Grein, Timothy AU - Grein T AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. FAU - Thomas, Anita AU - Thomas A AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. FAU - Juengel, Eva AU - Juengel E AUID- ORCID: 0000-0002-6321-8707 AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. FAU - Chun, Felix K-H AU - Chun FK AD - Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany. FAU - Cinatl, Jindrich AU - Cinatl J AD - Institute of Medical Virology, University Hospital, Goethe-University, 60596 Frankfurt am Main, Germany. FAU - Haferkamp, Axel AU - Haferkamp A AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. FAU - Tsaur, Igor AU - Tsaur I AUID- ORCID: 0000-0001-5107-3523 AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. FAU - Blaheta, Roman A AU - Blaheta RA AUID- ORCID: 0000-0002-0129-7972 AD - Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany. LA - eng GR - 201707660003/the Brigitta & Norbert Muth Stiftung, Wiesbaden, Germany, the Eden-Stiftung, Bad Soden, Germany, the Brigitte und Dr. Konstanze Wegener-Stiftung, Dusseldorf, Germany, and the China Scholarship Council/ PT - Journal Article DEP - 20220926 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC9564120 OTO - NOTNLM OT - AKT/mTOR OT - bladder cancer OT - drug resistance OT - proliferation OT - sulforaphane COIS- The authors declare no conflict of interest. EDAT- 2022/10/15 06:00 MHDA- 2022/10/15 06:01 PMCR- 2022/09/26 CRDT- 2022/10/14 01:51 PHST- 2022/08/25 00:00 [received] PHST- 2022/09/20 00:00 [revised] PHST- 2022/09/21 00:00 [accepted] PHST- 2022/10/14 01:51 [entrez] PHST- 2022/10/15 06:00 [pubmed] PHST- 2022/10/15 06:01 [medline] PHST- 2022/09/26 00:00 [pmc-release] AID - cancers14194682 [pii] AID - cancers-14-04682 [pii] AID - 10.3390/cancers14194682 [doi] PST - epublish SO - Cancers (Basel). 2022 Sep 26;14(19):4682. doi: 10.3390/cancers14194682.