PMID- 38499507 OWN - NLM STAT- MEDLINE DCOM- 20240416 LR - 20240416 IS - 1095-8355 (Electronic) IS - 1065-6995 (Linking) VI - 48 IP - 5 DP - 2024 May TI - Silver nanoparticles stimulate 5-Fluorouracil-induced colorectal cancer cells to kill through the upregulation TRPV1-mediated calcium signaling pathways. PG - 712-725 LID - 10.1002/cbin.12141 [doi] AB - The involvement of the TRP vanilloid 1 (TRPV1) cation channel on the 5-Fluorouracil (5-FU)-caused Ca(2+) signals through the activation of the apoptotic signaling pathway and stimulating the mitochondrial Ca(2+) and Zn(2+) accumulation-induced reactive oxygen species (ROS) productions in several cancer cells, except the colorectal cancer (HT-29) cell line, was recently reported. I aimed to investigate the action of silver nanoparticles (SiNPs) and 5-FU incubations through the activation of TRPV1 on ROS, apoptosis, and cell death in the HT-29 cell line. The cells were divided into four groups: control, SiNP (100 microM for 48 h), 5-FU (25 muM for 24 h), and 5-FU + SiNP. SiNP treatment through TRPV1 activation (via capsaicin) stimulated the oxidant and apoptotic actions of 5-FU in the cells, whereas they were diminished in the cells by the TRPV1 antagonist (capsazepine) treatment. The apoptotic and cell death actions of 5-FU were determined by increasing the propidium iodide/Hoechst rate, caspase-3, -8, and -9 activations, mitochondrial membrane depolarization, lipid peroxidation, and ROS, but decreasing the glutathione and glutathione peroxidase. The increase of cytosolic free Ca(2+) and Zn(2+) into mitochondria via the stimulation of TRPV1 current density increased oxidant and apoptotic properties of 5-FU in the cells. For the therapy of HT-29 tumor cells, I found that the combination of SiNPs and 5-FU was synergistic via TRPV1 activation. CI - (c) 2024 International Federation of Cell Biology. FAU - Kaya, Muge Mavioglu AU - Kaya MM AUID- ORCID: 0000-0003-1276-3745 AD - Department of Molecular Biology and Genetics, Faculty of Science, Kafkas University, Kars, Turkiye. LA - eng GR - 2022-03/BSN Health, Analysis and Innovation Ltd. Goller Bolgesi Teknokenti, Isparta, Turkiye/ PT - Journal Article DEP - 20240318 PL - England TA - Cell Biol Int JT - Cell biology international JID - 9307129 RN - 0 (Reactive Oxygen Species) RN - U3P01618RT (Fluorouracil) RN - 3M4G523W1G (Silver) RN - 0 (Antineoplastic Agents) RN - 0 (Oxidants) RN - SY7Q814VUP (Calcium) RN - 0 (TRPV1 protein, human) RN - 0 (TRPV Cation Channels) SB - IM MH - Humans MH - Reactive Oxygen Species/metabolism MH - Fluorouracil/pharmacology MH - Oxidative Stress MH - Silver/pharmacology MH - Calcium Signaling MH - *Metal Nanoparticles MH - Up-Regulation MH - *Antineoplastic Agents/pharmacology MH - Apoptosis MH - Oxidants/pharmacology MH - *Colorectal Neoplasms/drug therapy MH - Calcium/metabolism MH - TRPV Cation Channels/metabolism OTO - NOTNLM OT - 5-Fluorouracil OT - TRPV1 channel OT - apoptosis OT - colorectal cancer OT - mitochondria OT - silver nanoparticles EDAT- 2024/03/19 06:43 MHDA- 2024/04/16 12:43 CRDT- 2024/03/19 00:03 PHST- 2024/01/25 00:00 [revised] PHST- 2023/10/05 00:00 [received] PHST- 2024/02/05 00:00 [accepted] PHST- 2024/04/16 12:43 [medline] PHST- 2024/03/19 06:43 [pubmed] PHST- 2024/03/19 00:03 [entrez] AID - 10.1002/cbin.12141 [doi] PST - ppublish SO - Cell Biol Int. 2024 May;48(5):712-725. doi: 10.1002/cbin.12141. Epub 2024 Mar 18.