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Apoptosis of colon cancer cells under the effect of geldanamycin derivate
Aim:
The apoptotic effect of geldanamycin derivative may be important for the colorectal cancer therapy. The mechanisms of apoptosis require understanding of the behavior of colon cancer cell line Colo-205 which mimics colon adenocarcinoma. Therefore, the effect of IC50 dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on the colon cancer cells in vitro was studied for its anti-apoptotic activity.
Method:
Apoptotic ratio of the Colo-205 cells was determined after 17-AAG application with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and apoptosis related genes. Apoptosis signal path related key mitochondrial proteins, cytochrome c, bcl-2, caspase 9 and Apaf-1 expression were examined with RT-PCR method.
Results:
17-AAG caused induction of cell death. Apoptotic related genes such as cytochrome-c, Apaf-1 and caspase-9 protein expressions were increased significantly (p < 0.05) and anti-apoptotic bcl-2 expression was decreased significantly (p < 0.05). Our results indicated that the application of 17-AAG on Colo-205 cells showed anticancer effect by the apoptosis due to alteration of apoptotic genes.
Conclusion:
The apoptotic effect of 17-AAG as an natural product for alternative medicine would be very important for the success and quality of life during the treatment of colon carcinoma with the combination of anticancer drugs (Tab. 1, Fig. 2, Ref. 32).
Insights
17-allylamino-17-demethoxygeldanamycin (17-AAG) induces cell death in colon cancer cells by promoting apoptosis. This geldanamycin derivative alters apoptotic gene expression, showing potential as an anticancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Colorectal cancer therapy can benefit from understanding apoptotic mechanisms.
- Colon cancer cell line Colo-205 mimics colon adenocarcinoma, making it a suitable model.
- Geldanamycin derivatives, like 17-AAG, show promise in cancer treatment.
Purpose of the Study:
- To investigate the in vitro anti-apoptotic activity of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on the Colo-205 colon cancer cell line.
- To understand the molecular mechanisms underlying 17-AAG's effect on colon cancer cells.
Main Methods:
- Determined the apoptotic ratio of Colo-205 cells using TUNEL staining after 17-AAG treatment.
- Analyzed the expression of apoptosis-related genes (cytochrome c, bcl-2, caspase 9, Apaf-1) via RT-PCR.
Main Results:
- 17-AAG significantly increased the expression of pro-apoptotic genes (cytochrome c, Apaf-1, caspase-9) (p < 0.05).
- 17-AAG significantly decreased the expression of the anti-apoptotic gene bcl-2 (p < 0.05).
- The study observed a significant induction of cell death in Colo-205 cells treated with 17-AAG.
Conclusions:
- 17-AAG demonstrates anticancer effects on colon cancer cells by inducing apoptosis through the modulation of key apoptotic genes.
- The findings suggest 17-AAG's potential as an alternative medicine agent for colon carcinoma treatment, possibly in combination therapies.
