Generation of Reactive Oxygen Species during Apoptosis Induced by DNA-Damaging Agents and/or Histone Deacetylase Inhibitors

Abstract

Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism with histone deacetylase inhibitors butyrate or SAHA is also reported. We found that in cancer cell line, ROS production significantly contributed to apoptosis triggering, while in normal lymphocytes treated by cytostatic or cytotoxic drugs, necrosis as well as apoptosis occurred and large heterogeneity of ROS production was measured. Combined treatment with histone deacetylase inhibitor did not potentiate actinomycin D action, whereas combination of decitabine and SAHA brought synergistic ROS generation and apoptotic features in CML cell line. Appropriate decrease of cell viability indicated promising therapeutic potential of this combination in CML, but side effects on normal PBL should be taken into attention.

The role of DNA damage and repair in decitabine-mediated apoptosis in multiple myeloma

“…Similar to previous studies, we observed that the combination between decitabine and the HDACi JNJ-585 had synergistic anti-MM effects which were associated with enhanced caspase, PARP-1 and MCL-1 cleavage compared to either agent alone [25-28, 49]. We also confirmed the combinatory effects of decitabine and JNJ-585 in vivo .…”

Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells

“…Overproduction of ROS leads to oxidative stress and plays an important role in the process of apoptosis in many cell types [28], which can be ameliorated by endogenous and exogenous antioxidants. Bupivacaine was shown to induce ROS generation in SH-SY5Y cells [6], while GB reduced ROS levels in vivo [22], suggesting that GB may protect against bupivacaine toxicity by suppressing ROS accumulation.…”

4′-Demethyl-deoxypodophyllotoxin glucoside isolated from Podophyllum hexandrum exhibits potential anticancer activities by altering Chk-2 signaling pathway in MCF-7 breast cancer cells

“…ROS production confers mitochondrial damage as well as DNA damage, which is the characteristic features of most leading anticancer drugs like; paclitaxel, cisplatin, doxorubicin and natural compounds, Quercetin, EGCG, curcumin etc [15]. As an anticancer lead, 5 was able to generate sufficient ROS in MCF-7 cells at a concentration of 0.5 lM, which was comparable to positive control H 2 O 2 (10 lM) and better than 1 (5.0 lM) (Fig.…”

“…The Intracellular ROS level was measured by detecting the conversion of cell permeable 2 0 ,7 0 -dichlorofluorescien diacetate (DCFDA) to fluorescent dichlorofluorescein (DCF) [15]. Briefly, MCF-7 cells were seeded in 12-well plate and treated by the subtoxic concentrations of compounds 1, 5, vehicle DMSO and H 2 O 2 as positive control for 24 h. Two hours before the completion, H 2 O 2 was added to the medium.…”