Location
Philadelphia, PA
Start Date
1-5-2024 1:00 PM
End Date
1-5-2024 4:00 PM
Description
Introduction
Doxorubicin (DOX) is a well-known chemotherapy drug for various cancers, including breast cancer. However, DOX-induced cardiotoxicity set a significant barrier limiting its clinical application. Dexrazoxane (Dex) is the only FDA-approved drug to protect the heart against DOX-associated damage. Nonetheless, it is still arguable if Dex induces secondary malignancy. Our lab previously showed that pretreating H9c2 myoblast with a mitochondrial-targeted antioxidant, mitoquinone (MitoQ), demonstrated significantly higher cell viability than cotreatment with DOX. Still, whether MitoQ pretreatment or cotreatment would potentiate DOX’s efficacy on cancer cells is unclear. Furthermore, it is intriguing to evaluate if MitoQ’s effects on DOX’s anti-tumor capacity are comparable to Dex’s.
Methods
MCF7 breast cancer cells (6 x 104/well) were seeded in 96-well black plates. For the first set of experiments, cells were treated with DOX (0.5-200 µM, n=10), MitoQ (0.005 µM -20 µM, n=6), or Dex (1 µM – 500 µM, n=6), respectively. For the second set of experiments, cells were given MitoQ (0.005 µM -20 µM; n=5) or Dex (1 µM – 500 µM; n=3-4) with DOX (40 µM) concurrently (i.e., cotreatment) or 24 hours before the addition of 40 µM DOX (i.e., pretreatment). Cell morphology was monitored under the microscope after treating cells for 24 hours. The cell viability was evaluated by measuring absorbance at 450 nm after adding a cell counting reagent. The data were expressed as a ratio relative to untreated control.
Results
DOX dose-dependently reduced the viability of MCF7 cells. DOX started to reduce cell viability to 73±8% (n=10) at 10 µM, then 61±6% (n=10) at 40 µM, and 21±3% (n=5) at 200 µM when compared to nontreated control. By contrast, lower doses of MitoQ (0.005 µM – 5 µM, n=6) and Dex (1 µM - 10 µM, n=6) showed a slight increase in cell viability. At higher doses, MitoQ 10 µM and 20 µM decreased cell viability to 65±10% and 17±4% (n=6), respectively. By contrast, Dex only slightly attenuated cell viability to 83±3% at 200 µM and 74±7% at 500 µM (n=6). When MitoQ (0.005 µM – 10 µM, n=5) was given as pretreatment with DOX (40 µM, n=5), cell viability (52-73%) remained similar to DOX alone. Cell viability of MitoQ (20 µM) was 22±5%, close to MitoQ alone. On the other hand, Dex (1 µM - 500 µM, n=4) pretreatment with DOX (40 µM) attenuated cell viability more than Dex or DOX alone. In particular, Dex (200 µM and 500 µM) pretreatment reduced cell viability to 27±5% and 27±4% (n=4), respectively. Opposed to this, only the highest dose of MitoQ (20 µM, n=5) or Dex (500 µM, n=3) given as cotreatment with DOX showed similar cell viability (20±5% and 58±3%, respectively) to MitoQ alone or DOX alone, respectively. The data suggest that DOX, MitoQ, and Dex induce cancer cell deaths. However, DOX shows a broader dose range than MitoQ and better efficacy than Dex. Dex pretreatment with DOX shows additive effects on anti-cancer capacity, whereas Dex cotreatment, MitoQ pretreatment and cotreatment fail to deliver similar effects.
Embargo Period
6-13-2024
Included in
Effects of Mitoquinone and Dexrazoxane on doxorubicin’s anti-tumor efficacy
Philadelphia, PA
Introduction
Doxorubicin (DOX) is a well-known chemotherapy drug for various cancers, including breast cancer. However, DOX-induced cardiotoxicity set a significant barrier limiting its clinical application. Dexrazoxane (Dex) is the only FDA-approved drug to protect the heart against DOX-associated damage. Nonetheless, it is still arguable if Dex induces secondary malignancy. Our lab previously showed that pretreating H9c2 myoblast with a mitochondrial-targeted antioxidant, mitoquinone (MitoQ), demonstrated significantly higher cell viability than cotreatment with DOX. Still, whether MitoQ pretreatment or cotreatment would potentiate DOX’s efficacy on cancer cells is unclear. Furthermore, it is intriguing to evaluate if MitoQ’s effects on DOX’s anti-tumor capacity are comparable to Dex’s.
Methods
MCF7 breast cancer cells (6 x 104/well) were seeded in 96-well black plates. For the first set of experiments, cells were treated with DOX (0.5-200 µM, n=10), MitoQ (0.005 µM -20 µM, n=6), or Dex (1 µM – 500 µM, n=6), respectively. For the second set of experiments, cells were given MitoQ (0.005 µM -20 µM; n=5) or Dex (1 µM – 500 µM; n=3-4) with DOX (40 µM) concurrently (i.e., cotreatment) or 24 hours before the addition of 40 µM DOX (i.e., pretreatment). Cell morphology was monitored under the microscope after treating cells for 24 hours. The cell viability was evaluated by measuring absorbance at 450 nm after adding a cell counting reagent. The data were expressed as a ratio relative to untreated control.
Results
DOX dose-dependently reduced the viability of MCF7 cells. DOX started to reduce cell viability to 73±8% (n=10) at 10 µM, then 61±6% (n=10) at 40 µM, and 21±3% (n=5) at 200 µM when compared to nontreated control. By contrast, lower doses of MitoQ (0.005 µM – 5 µM, n=6) and Dex (1 µM - 10 µM, n=6) showed a slight increase in cell viability. At higher doses, MitoQ 10 µM and 20 µM decreased cell viability to 65±10% and 17±4% (n=6), respectively. By contrast, Dex only slightly attenuated cell viability to 83±3% at 200 µM and 74±7% at 500 µM (n=6). When MitoQ (0.005 µM – 10 µM, n=5) was given as pretreatment with DOX (40 µM, n=5), cell viability (52-73%) remained similar to DOX alone. Cell viability of MitoQ (20 µM) was 22±5%, close to MitoQ alone. On the other hand, Dex (1 µM - 500 µM, n=4) pretreatment with DOX (40 µM) attenuated cell viability more than Dex or DOX alone. In particular, Dex (200 µM and 500 µM) pretreatment reduced cell viability to 27±5% and 27±4% (n=4), respectively. Opposed to this, only the highest dose of MitoQ (20 µM, n=5) or Dex (500 µM, n=3) given as cotreatment with DOX showed similar cell viability (20±5% and 58±3%, respectively) to MitoQ alone or DOX alone, respectively. The data suggest that DOX, MitoQ, and Dex induce cancer cell deaths. However, DOX shows a broader dose range than MitoQ and better efficacy than Dex. Dex pretreatment with DOX shows additive effects on anti-cancer capacity, whereas Dex cotreatment, MitoQ pretreatment and cotreatment fail to deliver similar effects.