Investigation of the Antioxidant Status in Multiple Myeloma Patients: Effects of Therapy

Mehdi, Wesen Adel; Zainulabdeen, Jwan A.; Mehde, Atheer Awad

doi:10.7314/apjcp.2013.14.6.3663

Cited by 38 publications

(38 citation statements)

References 23 publications

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“…Studies have declared the reduction in antioxidant capacity in patients with MM. This reduction in activity of antioxidants and involvement of oxidative stress in MM cancer are in line with the present study (39,40).…”

Section: Discussionsupporting

confidence: 78%

Elevated Serum 8-Hydroxy-2’-Deoxyguanosine, Nitrite, and Nitrate in Patients with Stage I Multiple Myeloma

et al. 2017

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Background: Reactive oxygen species are highly active intermediates, which lead to cellular damage during imbalance between oxidative stress/antioxidant towards oxidative stress. Free radicals have been proposed to have a crucial role in development and progression of human cancer. Objectives: The main aim of this study was to assess the changes in 8-hydroxy-deoxyguanosine (8-OHdG), nitrite (NO2-), and nitrate (NO3-) levels in patients with Stage I multiple myeloma (MM). Methods: The serum samples were obtained from 34 patients with stage I MM (22 males and 12 females at stage I) who were matched with healthy control group. Total serum of NO2-and NO3-levels, in addition to serum 8-OHdG levels, were assayed by using the commercial assay kit.

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Section: Discussionsupporting

confidence: 78%

Elevated Serum 8-Hydroxy-2’-Deoxyguanosine, Nitrite, and Nitrate in Patients with Stage I Multiple Myeloma

et al. 2017

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“…A recent report showed that basal GSH levels are significantly elevated in MM patients after receiving therapy, which is consistent with our observation of resistant MM cell lines increasing GSH after L-PAM treatment. 56 Treatment with thiols (NAC and STS) antagonized the cytotoxic synergy of BSO+L-PAM, mimicking the effect of GSH as previously reported. 43, 57 The effect of NAC is independent of GSH because in the presence of BSO+L-PAM, NAC did not increase GSH levels.…”

Section: Discussionsupporting

confidence: 61%

The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma

Tagde

Singh

Kang

et al. 2014

Blood Cancer Journal

110

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Melphalan (L-PAM) has been an integral part of multiple myeloma (MM) treatment as a conditioning regimen before stem cell transplant (SCT). After initial response, most treated patients experience relapse with an aggressive phenotype. Increased glutathione (GSH) in MM may mediate resistance to L-PAM. We demonstrated that the GSH synthesis inhibitor buthionine sulfoximine (BSO) synergistically enhanced L-PAM activity (inducing 2–4 logs of cell kill) against nine MM cell lines (also in the presence of marrow stroma or cytokines) and in seven primary MM samples (combination indices <1.0). In MM cell lines, BSO significantly (P<0.05) depleted GSH, increased L-PAM-induced single-strand DNA breaks, mitochondrial depolarization, caspase cleavage and apoptosis. L-PAM depleted GSH, but GSH rapidly recovered in a L-PAM-resistant MM cell line unless also treated with BSO. Treatment with N-acetylcysteine antagonized BSO+L-PAM cytotoxicity without increasing GSH. In human MM xenografted into beige-nude-xid mice, BSO significantly depleted MM intracellular GSH and significantly increased apoptosis compared with L-PAM alone. BSO+L-PAM achieved complete responses (CRs) in three MM xenograft models including maintained CRs >100 days, and significantly increased the median event-free survival relative to L-PAM alone. Combining BSO with L-PAM warrants clinical testing in advanced MM.

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“…High oxidative stress and DNA damage activity are increased, while the anti-oxidant enzyme levels are decreased in MM patients (Mehdi et al, 2013). Several free radical drugs, such as As 2 O 3 and ascorbic acid, have been used to treat MM, in which As 2 O 3 generates ROS while ascorbic acid serves as an anti-oxidant agent.…”

Section: Discussionmentioning

confidence: 99%

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

Xia

Zhang

et al. 2017

EBioMedicine

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High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138+ MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients. PAA alone or in combination with melphalan inhibits tumor formation in MM xenograft mice. This study shows PAA efficacy on primary cancer cells and cell lines in vitro and in vivo.

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Investigation of the Antioxidant Status in Multiple Myeloma Patients: Effects of Therapy

Cited by 38 publications

References 23 publications

Elevated Serum 8-Hydroxy-2’-Deoxyguanosine, Nitrite, and Nitrate in Patients with Stage I Multiple Myeloma

Elevated Serum 8-Hydroxy-2’-Deoxyguanosine, Nitrite, and Nitrate in Patients with Stage I Multiple Myeloma

The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

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