Abstract

Malignant melanoma is the deadliest form of skin cancer, known for its drug resistance and high metastatic potential. Deregulated PI3 and mitogen activated protein (MAP) kinase pathways promote early melanocytic lesion development and confer drug resistance. No agent exists to target these deregulated pathways to prevent cutaneous noninvasive melanocytic cells or invasive melanomas from developing into more aggressive widely disseminated metastatic disease. In this study, a selenium containing isosteric analogue of PBIT [S,S′-1,4- phenylenebis(1,2-ethanediyl)bis-isothiourea] called PBISe [Se,Se′-1,4- phenylenebis(1,2-ethanediyl)bis-isoselenourea] is shown to moderate these 2 major signaling pathways to prevent cutaneous melanocytic lesion or melanoma development. Topical application of PBISe retarded melanocytic lesion development in laboratory-generated skin by 70% to 80% and in animal skin by approximately 50%. Mechanistically, prevention of lesion development occurred due to decreased Akt3 signaling, which increased MAP kinase pathway activity to inhibitory levels. The combined effect of targeting these pathways led to decreased cell proliferation and increased apoptotic cell death thereby preventing melanoma development. Thus, topically applied PBISe treatment has potential to prevent noninvasive melanocytic lesion and invasive metastatic melanoma development in skin.

Original languageEnglish (US)
Pages (from-to)935-948
Number of pages14
JournalCancer Prevention Research
Volume4
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Melanoma
Skin
Mitogen-Activated Protein Kinases
Drug Resistance
Skin Neoplasms
Selenium
Cell Death
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Chung, Chin Ying ; Madhunapantula, SubbaRao V. ; Desai, Dhimant ; Amin, Shantu ; Robertson, Gavin. / Melanoma prevention using topical PBISe. In: Cancer Prevention Research. 2011 ; Vol. 4, No. 6. pp. 935-948.
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abstract = "Malignant melanoma is the deadliest form of skin cancer, known for its drug resistance and high metastatic potential. Deregulated PI3 and mitogen activated protein (MAP) kinase pathways promote early melanocytic lesion development and confer drug resistance. No agent exists to target these deregulated pathways to prevent cutaneous noninvasive melanocytic cells or invasive melanomas from developing into more aggressive widely disseminated metastatic disease. In this study, a selenium containing isosteric analogue of PBIT [S,S′-1,4- phenylenebis(1,2-ethanediyl)bis-isothiourea] called PBISe [Se,Se′-1,4- phenylenebis(1,2-ethanediyl)bis-isoselenourea] is shown to moderate these 2 major signaling pathways to prevent cutaneous melanocytic lesion or melanoma development. Topical application of PBISe retarded melanocytic lesion development in laboratory-generated skin by 70{\%} to 80{\%} and in animal skin by approximately 50{\%}. Mechanistically, prevention of lesion development occurred due to decreased Akt3 signaling, which increased MAP kinase pathway activity to inhibitory levels. The combined effect of targeting these pathways led to decreased cell proliferation and increased apoptotic cell death thereby preventing melanoma development. Thus, topically applied PBISe treatment has potential to prevent noninvasive melanocytic lesion and invasive metastatic melanoma development in skin.",
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Melanoma prevention using topical PBISe. / Chung, Chin Ying; Madhunapantula, SubbaRao V.; Desai, Dhimant; Amin, Shantu; Robertson, Gavin.

In: Cancer Prevention Research, Vol. 4, No. 6, 01.06.2011, p. 935-948.

Research output: Contribution to journalArticle

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AU - Amin, Shantu

AU - Robertson, Gavin

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