PMID- 38004099
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231127
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 15
IP  - 22
DP  - 2023 Nov 7
TI  - The Role of Cyanidin-3-O-glucoside in Modulating Oxaliplatin Resistance by 
      Reversing Mesenchymal Phenotype in Colorectal Cancer.
LID - 10.3390/nu15224705 [doi]
LID - 4705
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) plays an important role in 
      the biological and biochemical processes of cells, and it is a critical process 
      in the malignant transformation, and mobility of cancer. Additionally, EMT is one 
      of the main mechanisms contributing to chemoresistance. Resistance to oxaliplatin 
      (OXA) poses a momentous challenge in the chemotherapy of advanced colorectal 
      cancer (CRC) patients, highlighting the need to reverse drug resistance and 
      improve patient survival. In this study, we explored the response of 
      cyanidin-3-O-glucoside (C3G), the most abundant anthocyanin in plants, on the 
      mechanisms of drug resistance in cancer, with the purpose of overcoming acquired 
      OXA resistance in CRC cell lines. METHODS: We generated an acquired OXA-resistant 
      cell line, named HCT-116-ROx, by gradually exposing parental HCT-116 cells to 
      increasing concentrations of OXA. To characterize the resistance, we performed 
      cytotoxicity assays and shape factor analyses. The apoptotic rate of both 
      resistant and parental cells was determined using Hoechst 33342/Propidium Iodide 
      (PI) fluorescence staining. Migration capacity was evaluated using a 
      wound-healing assay. The mesenchymal phenotype was assessed through qRT-PCR and 
      immunofluorescence staining, employing E-cadherin, N-cadherin, and Vimentin 
      markers. RESULTS: Resistance characterization announced decreased OXA sensitivity 
      in resistant cells compared to parental cells. Moreover, the resistant cells 
      exhibited a spindle cell morphology, indicative of the mesenchymal phenotype. 
      Combined treatment of C3G and OXA resulted in an augmented apoptotic rate in the 
      resistant cells. The migration capacity of resistant cells was higher than 
      parental cells, while treatment with C3G decreased the migration rate of 
      HCT-116-ROx cells. Analysis of EMT markers showed that HCT-116-ROx cells 
      exhibited loss of the epithelial phenotype (E-cadherin) and gain of the 
      mesenchymal phenotype (N-cadherin and Vimentin) compared to HCT-116 cells. 
      However, treatment of resistant cells with C3G reversed the mesenchymal 
      phenotype. CONCLUSION: The morphological observations of cells acquiring 
      oxaliplatin resistance indicated the loss of the epithelial phenotype and the 
      acquisition of the mesenchymal phenotype. These findings suggest that EMT may 
      contribute to acquired OXA resistance in CRC. Furthermore, C3G decreased the 
      mobility of resistant cells, and reversed the EMT process, indicating its 
      potential to overcome acquired OXA resistance.
FAU - Kurter, Hasan
AU  - Kurter H
AD  - Department of Translational Oncology, Institute of Health Sciences, Dokuz Eylul 
      University, Izmir 35330, Turkey.
FAU - Basbinar, Yasemin
AU  - Basbinar Y
AD  - Department of Translational Oncology, Institute of Oncology, Dokuz Eylul 
      University, Izmir 35330, Turkey.
FAU - Ellidokuz, Hulya
AU  - Ellidokuz H
AD  - Department of Preventive Oncology, Institute of Oncology, Dokuz Eylul University, 
      Izmir 35330, Turkey.
FAU - Calibasi-Kocal, Gizem
AU  - Calibasi-Kocal G
AD  - Department of Translational Oncology, Institute of Oncology, Dokuz Eylul 
      University, Izmir 35330, Turkey.
LA  - eng
GR  - 2020.KB.SAG.039/Dokuz Eylul University Scientific Research Coordination Unit/
PT  - Journal Article
DEP - 20231107
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 04ZR38536J (Oxaliplatin)
RN  - 7732ZHU564 (cyanidin)
RN  - 0 (Anthocyanins)
RN  - 0 (Vimentin)
RN  - 0 (Cadherins)
RN  - 0 (Glucosides)
SB  - IM
MH  - Humans
MH  - Oxaliplatin/pharmacology/therapeutic use
MH  - Anthocyanins/pharmacology/therapeutic use
MH  - Vimentin/metabolism
MH  - Cell Line, Tumor
MH  - *Colorectal Neoplasms/drug therapy/genetics/pathology
MH  - Cadherins/metabolism
MH  - Phenotype
MH  - *Biochemical Phenomena
MH  - Glucosides/pharmacology/therapeutic use
MH  - Epithelial-Mesenchymal Transition
MH  - Drug Resistance, Neoplasm
MH  - Cell Movement
PMC - PMC10674439
OTO - NOTNLM
OT  - colorectal cancer
OT  - cyanidin-3-O-glucoside
OT  - epithelial-mesenchymal transition
OT  - oxaliplatin resistance
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/25 12:44
MHDA- 2023/11/27 16:18
PMCR- 2023/11/07
CRDT- 2023/11/25 01:20
PHST- 2023/09/25 00:00 [received]
PHST- 2023/10/11 00:00 [revised]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2023/11/27 16:18 [medline]
PHST- 2023/11/25 12:44 [pubmed]
PHST- 2023/11/25 01:20 [entrez]
PHST- 2023/11/07 00:00 [pmc-release]
AID - nu15224705 [pii]
AID - nutrients-15-04705 [pii]
AID - 10.3390/nu15224705 [doi]
PST - epublish
SO  - Nutrients. 2023 Nov 7;15(22):4705. doi: 10.3390/nu15224705.