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

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

doi:10.1038/jid.1993.41

Cited by 18 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Uniquely high expression of TYR in melanoma compels the design and attachment of tyrosine-like prodrugs to mitotic kinase inhibitors. Although the concept of TYR-activated prodrugs has permeated the drug delivery literature for some time [134][135][136], it has yet to be applied to the delivery of mitotic kinase inhibitors. There are two themes notable in the TYR prodrug development field: attachment to DNA-damaging agents [135,137] and dormant compounds that become cytotoxic upon oxidation by tyrosinase [138].…”

Section: Example 1: Tyrosinase Is Highly Expressed In Melanomamentioning

confidence: 99%

Why Great Mitotic Inhibitors Make Poor Cancer Drugs

et al. 2020

View full text Add to dashboard Cite

Chemotherapy is central to oncology, perceived to operate only on prolific cancerous tissue. Yet, many non-neoplastic tissues are more prolific compared with typical tumors. Chemotherapies achieve sufficient therapeutic windows to exert antineoplastic activity because they are prodrugs that are bioactivated in cancer-specific environments. The advent of precision medicine has obscured this concept, favoring the development of high-potency kinase inhibitors. Inhibitors of essential mitotic kinases exemplify this paradigm shift, but intolerable on-target toxicities in more prolific normal tissues have led to repeated failures in the clinic. Proliferation rates alone cannot be used to achieve cancer specificity. Here, we discuss integrating the cancer specificity of prodrugs from classical chemotherapeutics and the potency of mitotic kinase inhibitors to generate a class of highprecision cancer therapeutics. Genotoxic Chemotherapies Have High Impact in the Clinic, but Research Efforts now Focus on Molecular Targeted TherapiesChemotherapies inducing DNA damage remain the mainstay of cancer treatment. Such damage leads to double-stranded breaks, which trigger apoptosis during cell division [1-3]. It sometimes not fully appreciated how clinically impactful and transformative chemotherapeutic agents truly are, especially when used in combination. For example, the combination of cyclophosphamide with rituximab, vincristine, doxorubicin, and prednisone (R-CHOP) yields long-term remissions and even complete cures in certain cancers [4][5][6][7][8]. For glioblastoma (GBM), before the advent of temozolomide (TMZ), long-term survivorship was unheard of; now it is possible, even if only for a few patients [9].

show abstract

Section: Example 1: Tyrosinase Is Highly Expressed In Melanomamentioning

confidence: 99%

Why Great Mitotic Inhibitors Make Poor Cancer Drugs

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Oxidation of phenols by tyrosinase is the basis of pigmentation reactions, but the activity can also be used to activate prodrugs. 23 Specifically, tyrosinase catalyses the hydroxylation of l-tyrosine to l-Dopa and its subsequent oxidation to dopaquinone, which undergoes a series of cascade reactions leading to the synthesis of melanin in the melanocyte. 24,25 Tyrosinase The induction of tyrosinase involves many transcription factors including p53.…”

Section: Tyrosinase-related Mechanismsmentioning

confidence: 99%

Exploiting Tyrosinase Expression and Activity in Melanocytic Tumors

et al. 2011

View full text Add to dashboard Cite

Melanoma is an aggressive tumor that expresses the pigmentation enzyme tyrosinase. Tyrosinase expression increases during tumorigenesis, which could allow for selective treatment of this tumor type by strategies that use tyrosinase activity. Approaches targeting tyrosinase would involve gene transcription or signal transduction pathways mediated by p53 in a direct or indirect manner. Two pathways are proposed for exploiting tyrosinase expression: (a) a p53-dependent pathway leading to apoptosis or arrest and (b) a reactive oxygen species-mediated induction of endoplasmic reticulum stress in p53 mutant tumors. Both strategies could use tyrosinase-mediated activation of quercetin, a dietary polyphenol that induces the expression of p53 and modulates reactive oxygen species. In addition to antitumor signaling properties, activation of quercetin could complement conventional cancer therapy by the induction of phase II detoxification enzymes resulting in p53 stabilization and transduction of its downstream targets. In conclusion, recent advances in tyrosinase enzymology, prodrug chemistry, and modern chemotherapeutics present an intriguing and selective multitherapy targeting system where dietary bioflavonoids could be used to complement conventional cancer treatments.

show abstract

“…Melanin precursors are inherently cytotoxic through reacting with tyrosinase to form unstable quinone derivatives [4]. Thus, tyrosine analogues that are tyrosinase substrates can be good candidates for developing drugs to melanoma-targeting therapies [5]. N-propionyl and N-acetyl derivatives (NPr- and NAcCAP) of 4- S -cysteaminylphenol, that is, sulfur-amine analogue of tyrosine, were synthesized as possible melanoma-targeted drugs (Figure 1) and found to possess selective cytotoxic effects on in vivo and in vitro melanomas through the oxidative stress that derives from production of cytotoxic free radicals by interacting with tyrosinase within melanogenesis cascade [6–10].…”

Section: Introductionmentioning

confidence: 99%

Melanoma-Targeted Chemothermotherapy andIn SituPeptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles

Jimbow

Ishii-Osai

Itô

et al. 2013

Journal of Skin Cancer

Self Cite

View full text Add to dashboard Cite

Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system.

show abstract

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

Cited by 18 publications

References 0 publications

Why Great Mitotic Inhibitors Make Poor Cancer Drugs

Why Great Mitotic Inhibitors Make Poor Cancer Drugs

Exploiting Tyrosinase Expression and Activity in Melanocytic Tumors

Melanoma-Targeted Chemothermotherapy andIn SituPeptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles

Contact Info

Product

Resources

About