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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