Toosendanin-induced apoptosis of CMT-U27 is mediated through the mitochondrial apoptotic pathway
Yin Yang1,2, Chen Mei1, Hong Xian1
1Institute of Animal Husbandry and Veterinary Medicine, Beijing Municipal Academy of Agriculture and Forestry, Beijing, China.
Abstract:
Toosendanin (TSN) is an active compound from the fruit of Melia toosendan Sieb et Zucc. TSN has been shown to have broad-spectrum anti-tumour activities in human cancers. However, there are still many gaps in the knowledge of TSN on canine mammary tumours (CMT). CMT-U27 cells were used to select the optimal acting time and best concentration of TSN to initiate apoptosis. Cell proliferation, cell colony formation, cell migration and cell invasion were analysed. The expression of apoptosis-related genes and proteins were also detected to explore the mechanism of action of TSN. A murine tumour model was established to detect the effect of TSN treatments. The results showed that TSN decreased cell viability of migration and invasion, altered CMT-U27 cell morphology, and inhibited DNA synthesis. TSN-induced cell apoptosis by upregulating BAX, cleaved caspase-3, cleaved caspase-9, p53 and cytochrome C (cytosolic) protein expression, and downregulating Bcl-2 and cytochrome C (mitochondrial) expression. In addition, TSN increased the mRNA transcription levels of cytochrome C, p53 and BAX, and decreased the mRNA expression of Bcl-2. Furthermore, TSN inhibited the growth of CMT xenografts by regulating the expression of genes and proteins activated by the mitochondrial apoptotic pathway. In conclusion, TSN effectively inhibited cell proliferation, migration and invasion activity, as well as induced CMT-U27 cell apoptosis. The study provides a molecular basis for the development of clinical drugs and other therapeutic options.
Insights
Toosendanin (TSN) effectively inhibits canine mammary tumor (CMT) cell proliferation, migration, and invasion. This compound induces apoptosis by modulating key genes and proteins in the mitochondrial pathway, offering a potential therapeutic strategy.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Toosendanin (TSN) is a compound from Melia toosendan with known anti-tumor effects.
- Knowledge regarding TSN's efficacy against canine mammary tumors (CMT) is limited.
- Canine mammary tumors represent a significant health concern in veterinary oncology.
Purpose of the Study:
- To investigate the anti-tumor effects of TSN on canine mammary tumor cells (CMT-U27).
- To elucidate the molecular mechanisms underlying TSN's action, focusing on apoptosis.
- To evaluate TSN's therapeutic potential in a murine CMT xenograft model.
Main Methods:
- CMT-U27 cells were treated with varying concentrations and durations of TSN.
- Assays included cell viability, proliferation, colony formation, migration, and invasion.
- Apoptosis-related gene and protein expression (e.g., BAX, Bcl-2, caspase-3, p53, cytochrome C) were analyzed.
- A murine xenograft model was used to assess in vivo efficacy.
Main Results:
- TSN significantly reduced CMT-U27 cell viability, migration, and invasion.
- TSN treatment induced apoptosis by upregulating pro-apoptotic factors (BAX, cleaved caspase-3/9, p53, cytosolic cytochrome C) and downregulating anti-apoptotic factors (Bcl-2, mitochondrial cytochrome C).
- TSN inhibited tumor growth in vivo by activating the mitochondrial apoptotic pathway.
Conclusions:
- TSN demonstrates potent anti-proliferative, anti-migratory, and anti-invasive effects on CMT cells.
- TSN effectively induces apoptosis in CMT cells via the mitochondrial pathway.
- TSN shows promise as a therapeutic agent for canine mammary tumors, warranting further clinical investigation.
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