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Hydroquinone-induced apoptosis in HL-60 cells
Hiroshi Terasaka1, Sufi Reza Morshed, Ken Hashimoto
1Department of Oral Diagnosis, Meikai University School of Dentistry, Saitama, Japan.
Anticancer Research
|April 9, 2005
Summary
Hydroquinone (HQ) induces apoptosis in HL-60 cells by inhibiting MnSOD and activating the intrinsic apoptosis pathway. The antioxidant N-acetyl-L-cysteine (NAC) modulates HQ
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Hydroquinone (HQ) is a chemical compound with known cytotoxic effects.
- Understanding the precise mechanisms of HQ-induced apoptosis is crucial for assessing its toxicological profile.
- The role of oxidative stress and specific apoptotic pathways in HQ toxicity requires further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms underlying hydroquinone (HQ)-induced apoptosis in human promyelocytic leukemia (HL-60) cells.
- To examine the involvement of superoxide dismutase (SOD) activation and expression, and caspase activation in HQ toxicity.
- To assess the modulatory effects of the antioxidant N-acetyl-L-cysteine (NAC) on HQ-induced apoptosis.
Main Methods:
- HL-60 cells were treated with HQ to assess cytotoxicity, DNA fragmentation, SOD activation, SOD mRNA expression, and caspase activation (caspase-3, -8, -9).
- Electrophoresis and activity staining were used to analyze SOD fractions.
- Cytochrome c release and procaspase activation were measured in HQ-treated cells.
- The effects of NAC on HQ-induced cytotoxicity and apoptosis were evaluated.
Main Results:
- HQ reduced MnSOD activation and MnSOD mRNA expression more significantly than Cu/ZnSOD, suggesting early mitochondrial dysfunction and inhibition of MnSOD induction.
- HQ treatment led to rapid release of cytochrome c and activation of caspase-3 and -9, but not caspase-8, indicating activation of the intrinsic apoptosis pathway.
- NAC significantly reduced HQ-induced cytotoxicity. Interestingly, NAC enhanced caspase-3 activation at higher HQ concentrations, suggesting a co-catalytic role in promoting apoptosis.
Conclusions:
- Hydroquinone induces apoptosis in HL-60 cells primarily through the intrinsic pathway, involving mitochondrial dysfunction and inhibition of MnSOD.
- N-acetyl-L-cysteine modulates HQ-induced apoptosis, reducing cytotoxicity at lower concentrations and potentially enhancing apoptosis at higher concentrations by acting as a co-catalyst.
- These findings provide insights into the complex interplay between oxidative stress, mitochondrial function, and apoptosis in hydroquinone toxicity.