Alneanaey, R., Taha, N., Lebda, M., Hashem, A., Sultan, A. (2023). Oligomeric proanthocyanidin grape seed extracts inhibited oncogenic signaling crosstalk of ERK1/2, β-catenin, and STAT3 through apoptosis induction in human liver and breast cancer cell lines.. test, 19(1), 78-102. doi: 10.21608/blj.2023.317452
Rana H. Alneanaey; Nabil M. Taha; Mohamed A. Lebda; Aml E. Hashem; Ahmed S. Sultan. "Oligomeric proanthocyanidin grape seed extracts inhibited oncogenic signaling crosstalk of ERK1/2, β-catenin, and STAT3 through apoptosis induction in human liver and breast cancer cell lines.". test, 19, 1, 2023, 78-102. doi: 10.21608/blj.2023.317452
Alneanaey, R., Taha, N., Lebda, M., Hashem, A., Sultan, A. (2023). 'Oligomeric proanthocyanidin grape seed extracts inhibited oncogenic signaling crosstalk of ERK1/2, β-catenin, and STAT3 through apoptosis induction in human liver and breast cancer cell lines.', test, 19(1), pp. 78-102. doi: 10.21608/blj.2023.317452
Alneanaey, R., Taha, N., Lebda, M., Hashem, A., Sultan, A. Oligomeric proanthocyanidin grape seed extracts inhibited oncogenic signaling crosstalk of ERK1/2, β-catenin, and STAT3 through apoptosis induction in human liver and breast cancer cell lines.. test, 2023; 19(1): 78-102. doi: 10.21608/blj.2023.317452

Oligomeric proanthocyanidin grape seed extracts inhibited oncogenic signaling crosstalk of ERK1/2, β-catenin, and STAT3 through apoptosis induction in human liver and breast cancer cell lines.

Biochemistry Letters
Volume 19, Issue 1, 2023, Pages 78-102    PDF (860.16 K)
DOI: 10.21608/blj.2023.317452
Authors
Rana H. Alneanaey1; Nabil M. Taha1; Mohamed A. Lebda1; Aml E. Hashem1; Ahmed S. Sultan2, 3
1Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt
2Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
3Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC. USA.
Abstract
Background: The constitutively activated oncogenic signals of ERK, β-catenin, and signal transducer and activator of transcription-3 (STAT-3) are therapeutic targets in cancer treatment. The present study explored the anticancer mechanism of grape seed extract's polyphenolic compounds, Oligomeric-Proanthocyanidins (OPC-PACs), to combat oncogenic proliferative signaling crosstalk, as the precise mechanisms are not yet fully understood. Materials and Methods: The mechanistic anti-cancer effects of the OPC-PACs on oncogenic signaling crosstalk and apoptosis-induction were investigated, using liver and breast cancer cell lines (HepG2 and ZR-75-1), in vitro and by measuring tumor volume of MNU-induced mammary tumors, in vivo.  Results: Wst-1 assay demonstrated that the viability of OPC-PACs treated cells was significantly decreased in a concentration-dependent manner compared to the mock. The calculated IC50 was (63.1 ± 0.024 mg/ml) and (61.6 ± 0.016 mg/ml) for HepG2 and ZR-75-1, respectively. Furthermore, OPC-PAC treatment for 48 h induced cell morphological changes, histone release, increased caspase-3 activity, and inhibition of p-ERK, β-catenin, and STAT-3 expression with apoptosis induction in HepG2 and ZR-75-1 cell lines as well as inhibition of tumor volume in vivo.   In vivo, OPC-PAC treatment for 45 days significantly (p < 0.05) decreased the tumor size of MNU-induced mammary tumors by 28.7% compared to untreated-induced tumors.  In-vivo cytotoxicity assessment confirmed the safety of the OPC-PACs treatment. Conclusion: The present study introduces OPC-PAC extract as a natural, non-toxic, and significantly inhibited crosstalk involved in cell proliferation that might act as a promising protective compound for consideration in complementary therapy in human cancers.
Keywords
OPC-PACs; p-ERK, ZR-75-1, STAT-3, β-catenin, Grape seeds
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