Evaluation of the Anticancer Potential of Compound 107 via the VEGFA and VEGFR2 (KDR) Signaling Pathway in Colorectal Cancer: Integrative Analysis of Clinical, In Silico, and In Vitro Approaches
10 affiliations
- 1Department of Medical Biochemistry, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Türkiye
- 2Department of Chemistry and Chemical Prossesing Technologies, Yıldızeli Vocational School, Sivas Cumhuriyet University, 58140 Sivas, Türkiye
- 3Department of General Surgery, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Türkiye
- 4Department of Petroleum and Natural Gas Engineering, Faculty of Engineering, Şırnak University, 73000 Şırnak, Türkiye
- 5Department of Food Processing Technologies Services, Yıldızeli Vocational School, Sivas Cumhuriyet University, 58140 Sivas, Türkiye
- 6Department of Nursing, Faculty of Health Sciences, Şırnak University, 73000 Şırnak, Türkiye
- 7Industrial Chemistry Research Laboratory (ICRL), Baku State University, Z. Khalilov 33, Baku AZ 1148, Azerbaijan
- 8Islamic World Educational, Scientific and Cultural Organization (ICESCO), Biomedical Materials Department, Baku State University, Z. Khalilov 33, Baku AZ 1148, Azerbaijan
- 9Department of Histology and Embryology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Türkiye
- 10Department of Medical Pathology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Türkiye
Abstract
The VEGFA and VEGFR2/KDR signaling pathway is a major regulator of tumor angiogenesis and colorectal cancer (CRC) progression. This study investigated the anticancer effects of Compound 107 using integrated clinical, in vitro, and in silico approaches. VEGFA and KDR expression was evaluated in paired colorectal tumor and adjacent non-neoplastic tissues, while molecular docking and ADMET analyses were performed to characterize Compound 107. Its effects on viability, apoptosis, cell-cycle distribution, VEGFA/KDR gene expression, and VEGFA and VEGFR2 protein levels were assessed in HT-29 cells. VEGFA and KDR expression was significantly increased in CRC tissues by 1.98- and 2.02-fold, respectively (both p < 0.001), accompanied by increased protein immunoreactivity (both p < 0.0001). Compound 107 showed favorable predicted binding to VEGFA (−8.60 kcal/mol) and VEGFR2 (−8.30 kcal/mol), although ADMET analysis indicated limitations related to pharmacokinetic and toxicity profiles. Compound 107 reduced MTT-based metabolic viability in a concentration- and time-dependent manner, increased early apoptosis, decreased the G0/G1 population, and increased the S-phase population. Moreover, VEGFA and KDR gene expression and corresponding protein fluorescence intensities were significantly reduced following treatment. Collectively, Compound 107 reduced metabolic viability and increased early apoptosis, accompanied by reduced VEGFA and KDR expression in HT-29 cells. These findings indicate an association between the cellular effects of Compound 107 and changes in VEGFA/VEGFR2-related molecular markers; however, they do not demonstrate direct inhibition of the VEGFA/VEGFR2 signaling pathway. Further mechanistic studies are required to clarify this relationship.
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BibTeX
@article{tas2026evaluation,
title = {{Evaluation of the Anticancer Potential of Compound 107 via the VEGFA and VEGFR2 (KDR) Signaling Pathway in Colorectal Cancer: Integrative Analysis of Clinical, In Silico, and In Vitro Approaches}},
author = {Ayca Tas and Cemile Zontul and Gökhan Dogan and Hakki Coskun and Husnu Cagri Genc and Kenan Goren and Tugba Agbektas and Veysel Tahiroglu and Alakbar Huseynzada and Ulviyya Hasanova and Gonca Kabak and Zeynep Deniz Sahin Inan and Hatice Ozer and Yavuz Silig},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219621},
url = {https://www.mdpi.com/1422-0067/27/21/9621},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evaluation of the Anticancer Potential of Compound 107 via the VEGFA and VEGFR2 (KDR) Signaling Pathway in Colorectal Cancer: Integrative Analysis of Clinical, In Silico, and In Vitro Approaches
AU - Ayca Tas
AU - Cemile Zontul
AU - Gökhan Dogan
AU - Hakki Coskun
AU - Husnu Cagri Genc
AU - Kenan Goren
AU - Tugba Agbektas
AU - Veysel Tahiroglu
AU - Alakbar Huseynzada
AU - Ulviyya Hasanova
AU - Gonca Kabak
AU - Zeynep Deniz Sahin Inan
AU - Hatice Ozer
AU - Yavuz Silig
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219621
UR - https://www.mdpi.com/1422-0067/27/21/9621
AB - The VEGFA and VEGFR2/KDR signaling pathway is a major regulator of tumor angiogenesis and colorectal cancer (CRC) progression. This study investigated the anticancer effects of Compound 107 using integrated clinical, in vitro, and in silico approaches. VEGFA and KDR expression was evaluated in paired colorectal tumor and adjacent non-neoplastic tissues, while molecular docking and ADMET analyses were performed to characterize Compound 107. Its effects on viability, apoptosis, cell-cycle distribution, VEGFA/KDR gene expression, and VEGFA and VEGFR2 protein levels were assessed in HT-29 cells. VEGFA and KDR expression was significantly increased in CRC tissues by 1.98- and 2.02-fold, respectively (both p < 0.001), accompanied by increased protein immunoreactivity (both p < 0.0001). Compound 107 showed favorable predicted binding to VEGFA (−8.60 kcal/mol) and VEGFR2 (−8.30 kcal/mol), although ADMET analysis indicated limitations related to pharmacokinetic and toxicity profiles. Compound 107 reduced MTT-based metabolic viability in a concentration- and time-dependent manner, increased early apoptosis, decreased the G0/G1 population, and increased the S-phase population. Moreover, VEGFA and KDR gene expression and corresponding protein fluorescence intensities were significantly reduced following treatment. Collectively, Compound 107 reduced metabolic viability and increased early apoptosis, accompanied by reduced VEGFA and KDR expression in HT-29 cells. These findings indicate an association between the cellular effects of Compound 107 and changes in VEGFA/VEGFR2-related molecular markers; however, they do not demonstrate direct inhibition of the VEGFA/VEGFR2 signaling pathway. Further mechanistic studies are required to clarify this relationship.
SN - 1422-0067
ER -