Elucidation of the therapeutic enhancer mechanism of poly-S-nitrosated human serum albumin against multidrug-resistant tumor in animal models

Ishima, Yu; Hara, Michiaki; Kragh‐Hansen, Ulrich; Inoue, A.; Suenaga, Atsushi; Kai, Toshiya; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

doi:10.1016/j.jconrel.2012.10.003

Cited by 21 publications

(25 citation statements)

References 25 publications

(38 reference statements)

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“…Tyrosine nitration of ABCC1 or lung-resistant protein, resistance-related proteins expressed in K562 cells, was not studied, even though both proteins were significantly decreased during the combined treatment with an NO-donor and daunorubicin. Ishima et al [91] have reported that poly-S-nitrosated human albumin, which may serve as a reservoir for * NO in vivo, increased doxorubicin intracellular concentration in a pgp-overexpressing K562-dx cells, resulting in the reversal of doxorubicin resistance in cells as well as in animals bearing K562-dx cells in vivo. It was found that poly-S-nitrosated albumin reversed doxorubicin resistance by decreasing the expression of pgp and HIF-1α in K562-dx cells.…”

Section: Reversal Of Drug Resistance By Nitric Oxidementioning

confidence: 99%

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Sinha

2016

J Cancer Sci Ther

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A successful treatment of cancers in the clinic has been difficult to achieve because of the emergence of drug resistant tumor cells. While various approaches have been tried to overcome multi-drug resistance, it has remained a major road block in achieving complete success in the clinic. Extensive research has identified various mechanisms, including overexpression of P-glycoprotein 170, modifications in activating or detoxification enzymes (phase I and II enzymes), and mutation and/or decreases in target enzymes in cancer cells. However, nitric oxide and/or nitric oxide-related species have not been considered an important player in cancer treatment and or drug resistance. Here, we examine the significance of nitric oxide in the treatment and resistance mechanisms of various anticancer drugs. Furthermore, we describe the significance of recently reported effects of nitric oxide on topoisomerases and the development of resistance to topoisomerase-poisons in tumor cells.Nitric oxide is also implicated in cancer cell killing, cancer progression and metastasis and poor survival [13][14][15][16][17]. A poor clinical outcome is believed to result from * NO-induced rapid tumor growth, resulting in hypoxia, nutrient deprivation, poor drug delivery, and selection for drug-resistant tumor cells. In vivo, * NO is formed from L-arginine by nitric oxide synthase (NOS). Three forms of NOS have been identified, including neuronal (nNOS), endothelial (eNOS), and a Ca 2+ -independent inducible isoform (iNOS). High expression of iNOS and increased production of • NO have been described in many human tumors, including breast, prostate and colorectal cancers [17][18][19][20]. Increased and continuous generation of * NO plays a significant role in the regulation of cancer cell progression and carcinogenesis. Hibbs et al. [21,22] and Stuehr and Nathan [23] have shown that co-culturing of leukemia L1210 cells with activated peritoneal macrophages results in the inhibition of L1210 cell proliferation which is correlated with nitrite formation. Inhibitors of NOS (L-NAME) and myoglobin, a scavenger of * NO 2 were effective in inhibiting cell killing actions of the activated macrophages, suggesting that * NO is responsible for the killing actions of activated macrophages towards cancer cells.It is believed that DNA damage and apoptosis induced by * NO in tumor cells cause tumor cell death; studies are needed to explore processes to deliver the highest concentrations of * NO in tumor cells using NO-donors as single chemotherapeutic agents or in combination with other chemotherapeutic agents. While significant progress has been made in the last decade, the role of * NO/ * NO-related species remains poorly understood in chemotherapy and drug resistance. Here, we review the role of * NO/ * NO-related species in cancer chemotherapy

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Section: Reversal Of Drug Resistance By Nitric Oxidementioning

confidence: 99%

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Sinha

2016

J Cancer Sci Ther

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“…Therefore, that potential effect was examined by flow cytometry [33]. We found that, after 1 h incubation with dx, the fluorescence intensity of dx in K562/dx cells was about 60% of that in K562 cells.…”

Section: Poly-sno-hsa Can Overcome Mdrmentioning

confidence: 99%

“…In order to explain the modulating effects of Poly-SNO-HSA on dx in K562/dx cells, we also analyzed the expression of P-gp by Western blotting [33]. The P-gp protein was strongly expressed in K562/dx cells, while it was not clearly detected in K562 cells.…”

Section: Poly-sno-hsa Can Overcome Mdrmentioning

confidence: 99%

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Poly-S-Nitrosated Albumin as a Safe and Effective Multifunctional Antitumor Agent: Characterization, Biochemistry and Possible Future Therapeutic Applications

Ishima

Kragh‐Hansen

Maruyama

et al. 2013

BioMed Research International

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Nitric oxide (NO) is a ubiquitous molecule involved in multiple cellular functions. Inappropriate production of NO may lead to disease states. To date, pharmacologically active compounds that release NO within the body, such as organic nitrates, have been used as therapeutic agents, but their efficacy is significantly limited by unwanted side effects. Therefore, novel NO donors with better pharmacological and pharmacokinetic properties are highly desirable. The S-nitrosothiol fraction in plasma is largely composed of endogenous S-nitrosated human serum albumin (Mono-SNO-HSA), and that is why we are testing whether this albumin form can be therapeutically useful. Recently, we developed SNO-HSA analogs such as SNO-HSA with many conjugated SNO groups (Poly-SNO-HSA) which were prepared using chemical modification. Unexpectedly, we found striking inverse effects between Poly-SNO-HSA and Mono-SNO-HSA. Despite the fact that Mono-SNO-HSA inhibits apoptosis, Poly-SNO-HSA possesses very strong proapoptotic effects against tumor cells. Furthermore, Poly-SNO-HSA can reduce or perhaps completely eliminate the multidrug resistance often developed by cancer cells. In this review, we forward the possibility that Poly-SNO-HSA can be used as a safe and effective multifunctional antitumor agent.

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“…To correct for nonspecific background fluorescence, the samples were analyzed using a standard curve made on the basis of tissue extracts derived from drug-free mice. The data are expressed as nanogram of DOX per mg of tissue protein or as µgram per ml of plasma[24].2.8. Effect of SNO-HSA-Dimer on solid tumor vascular permeabilityC26 tumors of three mice per group at 10 days after tumor cell inoculation were used for the in vivo vascular permeability experiments, as previously reported[22].…”

mentioning

confidence: 99%

S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes

Kinoshita

Ishima

Ikeda

et al. 2015

Journal of Controlled Release

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Elucidation of the therapeutic enhancer mechanism of poly-S-nitrosated human serum albumin against multidrug-resistant tumor in animal models

Cited by 21 publications

References 25 publications

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Nitric Oxide: Friend or Foe in Cancer Chemotherapy and Drug Resistance: A Perspective

Poly-S-Nitrosated Albumin as a Safe and Effective Multifunctional Antitumor Agent: Characterization, Biochemistry and Possible Future Therapeutic Applications

S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes

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