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Ginkgetin inhibits growth of breast carcinoma via regulating MAPKs pathway
Jun Cao1, Chuang Tong2, Yanyan Liu2
1Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Department of General Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei 230032,China.
Abstract:
The purpose of present study was to investigate anti-tumor activity of Ginkgetin (GK) and its mechanism of action in breast cancer. The effects of GK on growth of human breast cancer cell lines MDA-MB-231, BT-474 and MCF-7 were examined by MTT assay. Cells apoptosis in MCF-7 cells were analyzed by TUNEL staining and annexin-V and propidium iodide double staining. The effects of GK on expression of apoptotic associated proteins and mitogen-activated protein kinases (MAPKs) were determined by western blotting. The results showed that GK significantly inhibited proliferation of MDA-MB-231, BT-474 and MCF-7 cells in vitro with time and dose dependent manners and induced apoptosis in MCF-7 cells. GK treatment obviously induced the tumor cells apoptosis and inhibited tumor growth in the MCF-7 xenograft nude mice. GK increased expression of Bax, cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, and decreased the levels of Bcl-2 and survivin in MCF-7 cells. Moreover, GK treatment up-regulated expression of phospho extracellular-related kinase (p-ERK), p-p38 and phospho Jun-amino-terminal kinase (p-JNK) in MCF-7 cells in vitro, and increased numbers of p-p38, p-JNK and p-ERK positive cells in the tumor tissue in vivo. Strikingly, treatment of p38 inhibitor (or JNK inhibitor; ERK inhibitor) significantly prevented GK induced growth inhibition and apoptosis in MCF-7 cells. Collectively, our data exhibit GK exerts well anticancer effects in breast cancer cells, which at least in part, is via activation of the MAPKs. Our results provide a new approach for the treatment of breast cancer.
Insights
Ginkgetin (GK) demonstrates significant anti-tumor activity against breast cancer by inhibiting cell proliferation and inducing apoptosis. This action is mediated through the activation of mitogen-activated protein kinases (MAPKs) signaling pathways.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Breast cancer remains a leading cause of cancer-related deaths globally.
- Novel therapeutic agents with improved efficacy and reduced side effects are urgently needed.
- Ginkgetin (GK), a natural compound, has shown potential in preliminary studies.
Purpose of the Study:
- To investigate the anti-tumor activity of Ginkgetin (GK) in breast cancer.
- To elucidate the underlying mechanisms of GK's action, focusing on apoptosis and MAPK signaling.
Main Methods:
- MTT assay to assess cell proliferation in human breast cancer cell lines (MDA-MB-231, BT-474, MCF-7).
- TUNEL staining and Annexin-V/propidium iodide double staining for apoptosis analysis.
- Western blotting to evaluate protein expression of apoptotic markers and mitogen-activated protein kinases (MAPKs).
- In vivo studies using MCF-7 xenograft nude mice models.
Main Results:
- GK significantly inhibited the proliferation of MDA-MB-231, BT-474, and MCF-7 cells in a time- and dose-dependent manner.
- GK induced apoptosis in MCF-7 cells, evidenced by increased Bax, cleaved-caspase-3, -8, -9, and PARP, and decreased Bcl-2 and survivin.
- GK treatment activated MAPKs, including ERK, p38, and JNK, both in vitro and in vivo.
- Inhibition of MAPKs abrogated GK-induced growth inhibition and apoptosis in MCF-7 cells.
Conclusions:
- Ginkgetin (GK) exhibits potent anti-cancer effects against breast cancer cells.
- The anti-tumor activity of GK is mediated, at least in part, by the activation of the MAPK signaling pathways.
- GK represents a promising therapeutic candidate for breast cancer treatment.