Exploitation of Pigment Biosynthesis Pathway as a Selective Chemotherapeutic Approach for Malignant Melanoma

Jimbow, Kowichi; Iwashina, Takashi; Alena, Frank; Yamada, Koji; Pankovich, Jim; Umemura, Tadahiro

doi:10.1038/jid.1993.82

Cited by 26 publications

(16 citation statements)

References 26 publications

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“…The selective disintegration of melanocytes can be seen by electron microscopic examination as early as 12 h after a single ip administration. None of surrounding keratinocytes or fibroblasts showed membrane degeneration or cell death ( Figure 10 ) [ 32 , 33 ]. In experiments using melanoma-bearing mice, NAcCAP and NPrCAP were found to be selectively incorporated into melanoma transplants and retained within melanoma cells, exerting a cytotoxic effect through oxidative stress that may derive from the tyrosinase-catalyzed production of cytotoxic free radicals from the tyrosine analogs (chemotherapeutic effect) [ 34 ].…”

Section: Selective Inhibition Of Melanoma Growth By Nprcap/mnp Conjug...mentioning

confidence: 99%

Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review

Tamura

Ito

Wakamatsu

et al. 2022

IJMS

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A major advance in drug discovery and targeted therapy directed at cancer cells may be achieved by the exploitation and immunomodulation of their unique biological properties. This review summarizes our efforts to develop novel chemo-thermo-immunotherapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, the utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) expression upon heat generation in MNP by exposure to an alternating magnetic field (AMF). This comprehensive review covers experimental in vivo and in vitro mouse melanoma models and preliminary clinical trials with a limited number of advanced melanoma patients. We also discuss the future directions of CTI therapy.

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Section: Selective Inhibition Of Melanoma Growth By Nprcap/mnp Conjug...mentioning

confidence: 99%

Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review

Tamura

Ito

Wakamatsu

et al. 2022

IJMS

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“…Because the melanogenic pathway is found only in melanocytes, it is an attractive, selective target not only for therapeutic intervention in cancer but also for cosmetic control of skin pigmentation (Speeckaert et al, 2014;Regad, 2013). Tyrosinase inhibitors or false substrates of tyrosinase represent one approach to the development of anti-melanin drugs (Jimbow et al, 1993). Several classes of tyrosinase inhibitors / false substrates with potential antimelanotic activity have been identified, including 2-and 4-sulfur-substituted phenols (Riley et al, 1997;Jimbow et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of dialkylaminoaryl phosphonate bioisosteres of tyrosine and tyramine: a novel application of allene phosphonate chemistry for the synthesis of false substrates of tyrosinase

Mazzuca¹,

Angelov²,

Wiebe

2015

J App Pharm Sci

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Tyrosinase is the rate-limiting oxidase in the synthesis of melanin, making it an obvious target for the treatment of melanotic melanomas. Tyrosine and tyramine are its natural substrates, but many of their derivatives are inhibitors or false substrates, and are therefore prime candidates for melanoma chemotherapy. A series of dialkylphosphonate derivatives of tyramine have now been synthesized in order to extend the chemical diversity of tyrosinase substrates. The known reactivity between alkenephosphonates and nucleophiles was exploited by the addition of 4-(2-aminoethyl)phenol (tyramine) across the 2,3-double bond of 1,2-alkadiene phosphonates, to obtain the desired bisphosphonate derivatives. These reactions were highly chemoselective and regioselective but not stereoselective. Five of the reported novel dialkylphosphonate aminophenols were substrates for mushroom tyrosinase in vitro: dimethyl 2-[2(4-hydroxyphenyl)ethylamino]-3-methyl-1-butenephosphonate (3);diethyl 2-[2(4-hydroxyphenyl)ethylamino]-3-methyl-1-butenephosphonate (4);dimethyl 2-[2-(4hydroxyphenyl)ethylamino]-2-cyclohexyl-1-ethenephosphonate (5);diethyl 2-[2-(4-hydroxyphenyl)ethylamino]-2-cyclohexyl-1-ethenephosphonate (6);diethyl 2-[2-(4-hydroxyphenyl)ethylamino]ethanephosphonate (7). Compound 3 blocked the pigmentation of anagen hair in vivo in a murine animal model, a further demonstration that these compounds are able to enter and disrupt the melanogenic pathway.

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“…The current systemic therapies have little effect on the overall survival period or rate of advanced melanoma (Balch et al, 2001). Because melanogenesis is inherently toxic and uniquely expressed in melanocytic cells, tyrosine analogs can be good candidates for melanoma-specific targeting and therapy (Jimbow et al, 1993). To develop melanocytotoxic compounds for rational chemotherapy for melanoma, N-acetyl-cysteaminylphenol and N-propionyl-cysteaminylphenol (NPrCAP) were synthesized.…”

Section: Introductionmentioning

confidence: 99%

N-Propionyl-Cysteaminylphenol-Magnetite Conjugate (NPrCAP/M) Is a Nanoparticle for the Targeted Growth Suppression of Melanoma Cells

Sato

Yamashita

Ohkura

et al. 2009

Journal of Investigative Dermatology

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A magnetite nanoparticle, NPrCAP/M, was produced for intracellular hyperthermia treatment of melanoma by conjugating N-propionyl-cysteaminylphenol (NPrCAP) with magnetite and used for the study of selective targeting and degradation of melanoma cells. NPrCAP/M, like NPrCAP, was integrated as a substrate in the oxidative reaction by mushroom tyrosinase. Melanoma, but not non-melanoma, cells incorporated larger amounts of iron than magnetite from NPrCAP/M. When mice bearing a B16F1 melanoma and a lymphoma on opposite flanks were given NPrCAP/M, iron was observed only in B16F1 melanoma cells and iron particles (NPrCAP/M) were identified within late-stage melanosomes by electron microscopy. When cells were treated with NPrCAP/M or magnetite and heated to 43 degrees C by an external alternating magnetic field (AMF), melanoma cells were degraded 1.7- to 5.4-fold more significantly by NPrCAP/M than by magnetite. Growth of transplanted B16 melanoma was suppressed effectively by NPrCAP/M-mediated hyperthermia, suggesting a clinical application of NPrCAP/M to lesional therapy for melanoma. Finally, melanoma cells treated with NPrCAP/M plus AMF showed little sub-G1 fraction and no caspase 3 activation, suggesting that the NPrCAP/M-mediated hyperthermia induced non-apoptotic cell death. These results suggest that NPrCAP/M may be useful in targeted therapy for melanoma by inducing non-apoptotic cell death after appropriate heating by the AMF.

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Exploitation of Pigment Biosynthesis Pathway as a Selective Chemotherapeutic Approach for Malignant Melanoma

Cited by 26 publications

References 26 publications

Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review

Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review

Synthesis of dialkylaminoaryl phosphonate bioisosteres of tyrosine and tyramine: a novel application of allene phosphonate chemistry for the synthesis of false substrates of tyrosinase

N-Propionyl-Cysteaminylphenol-Magnetite Conjugate (NPrCAP/M) Is a Nanoparticle for the Targeted Growth Suppression of Melanoma Cells

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