Camptothecin, triptolide, and apoptosis inducer kit have differential effects on mitochondria in colorectal carcinoma
Veronika Liskova1, Marek Kajsik1,2, Barbora Chovancova1
1Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Abstract:
Mitochondrial fission and fusion are required for cell survival, and several studies have shown an imbalance between fission and fusion in cancer. High levels of mitochondrial fusion are observed in drug-resistant tumor cells, whereas mitochondrial fission may be important in sensitizing tumor cells to chemotherapy drugs. Based on current knowledge, we hypothesized that different chemotherapeutics might differentially affect mitochondrial dynamics and energy production. Thus, we selected chemotherapeutics with different mechanisms of action (camptothecin, triptolide and apoptosis inducer kit) and investigated their effect on mitochondria in colorectal carcinoma cells. We report that these chemotherapeutics decreased the activity of complex I and reduced the mitochondrial membrane potential, and also decreased the size of mitochondria in the colorectal carcinoma cell lines DLD1 and HCT-116. Treatment with camptothecin, triptolide and/or apoptosis inducer kit results in differential effects of fission on apoptosis in these cells. Our results suggest that fission is an important process in apoptosis induced by chemotherapeutics.
Insights
Chemotherapeutics alter mitochondrial dynamics, decreasing size and membrane potential in colorectal cancer cells. Mitochondrial fission is crucial for chemotherapy-induced apoptosis, offering new therapeutic insights.
Area of Science:
- Cell Biology
- Cancer Research
- Mitochondrial Biology
Background:
- Mitochondrial dynamics (fission and fusion) are vital for cell survival.
- Imbalances in mitochondrial dynamics are linked to cancer progression and drug resistance.
- Mitochondrial fission may enhance chemotherapy sensitivity in tumor cells.
Purpose of the Study:
- To investigate the differential effects of various chemotherapeutics on mitochondrial dynamics and energy production in colorectal carcinoma cells.
- To explore the role of mitochondrial fission in chemotherapy-induced apoptosis.
Main Methods:
- Treatment of colorectal carcinoma cell lines (DLD1, HCT-116) with chemotherapeutics: camptothecin, triptolide, and apoptosis inducer kit.
- Assessment of mitochondrial complex I activity and mitochondrial membrane potential.
- Analysis of mitochondrial size and dynamics (fission/fusion) in response to treatment.
Main Results:
- Chemotherapeutics significantly decreased complex I activity and mitochondrial membrane potential.
- All tested chemotherapeutics reduced mitochondrial size, indicating a shift towards fission.
- Differential effects of fission were observed in the induction of apoptosis by the chemotherapeutics.
Conclusions:
- Mitochondrial fission is a key process in the induction of apoptosis by chemotherapeutics in colorectal cancer cells.
- Targeting mitochondrial dynamics represents a potential strategy to enhance chemotherapy efficacy.
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