Journal Article

All-<i>trans</i> retinoic acid (atRA) differentially induces apoptosis in matched primary and metastatic melanoma cells – a speculation on damage effect of atRA via mitochondrial dysfunction and cell cycle redistribution

H. Zhang, K. Satyamoorthy, M. Herlyn and I. Rosdahl

in Carcinogenesis

Volume 24, issue 2, pages 185-191
Published in print February 2003 | ISSN: 0143-3334
Published online February 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.2.185
All-trans retinoic acid (atRA) differentially induces apoptosis in matched primary and metastatic melanoma cells – a speculation on damage effect of atRA via mitochondrial dysfunction and cell cycle redistribution

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All-trans retinoic acid (atRA) has been suggested to exert its cytotoxicity via apoptosis but the mechanisms behind the damage effects have not been fully understood. In this study, we investigated the cytotoxic effects of atRA in eleven primary and matched metastatic cutaneous melanoma cell lines. All the primary and metastatic melanoma cell lines examined expressed the retinoic acid receptors. The cultured melanoma cells treated with atRA showed dysfunction of mitochondria and altered cell cycle distribution, inhibited cell proliferation and apoptosis. The cytotoxic effects of atRA were dose- and time-dependent. The dysfunction of mitochondria and induction of apoptosis were more pronounced in the primary tumor cells than in the metastatic cell lines from the same patients. The data indicate that the cytotoxic effect of atRA was mediated through dysfunction of mitochondria, alterations in cell cycle and induction of apoptosis. Melanoma in early stage may have better response to atRA adjuvant therapy than the melanoma in late stage, suggesting the early utility of atRA in melanoma chemotherapy.

Journal Article.  4302 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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