Platinosomes produced in synovial membrane by platinum coordination complexes

Ghadially, F. N.; Lock, C. J. L.; Lalonde, J.-M. A.; Ghadially, Ruby

doi:10.1007/bf02889154

Cited by 9 publications

(9 citation statements)

References 8 publications

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“…It is also possible that cDDP is directly internalized from the extracellular milieu into melanosomes via endocytosis or phagocytosis, thus bypassing a cytoplasm to nucleus route. Supporting this is data showing that platinum compounds can be internalized via phagocytosis and that cells with impaired endocytosis have decreased intracellular accumulation of cDDP (35,36). Melanosome sequestration may act as a resistance modulator for other compounds, in addition to cDDP, through other drug-specific mechanisms.…”

Section: Discussionmentioning

confidence: 87%

Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes

et al. 2009

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Whereas resistance to chemotherapy has long impeded effective treatment of metastatic melanoma, the mechanistic basis of this resistance remains unknown. One possible mechanism of drug resistance is alteration of intracellular drug distribution either by drug efflux or sequestration into intracellular organelles. Melanomas, as well as primary melanocytes from which they arise, have intracellular organelles, called melanosomes, wherein the synthesis and storage of the pigment melanin takes place. In this study, comparisons of congenic cells with and without functional molecules regulating melanosome formation show that sensitivity to the chemotherapeutic agent cis-diaminedichloroplatinum II (cis-platin) significantly increases with the mutation of genes regulating melanosome formation, concomitant disruption of melanosome morphology, and loss of mature melanosomes. Absence of the melanosomal structural protein gp100/Pmel17 causes increased cis-platin sensitivity. Independent mutations in three separate genes that regulate melanosome biogenesis (Dtnbp1, Pldn, Vps33a) also result in increased cis-platin sensitivity. In addition, a mutation of the gene encoding the integral melanosomal protein tyrosinase, resulting in aberrant melanosome formation, also causes increased cis-platin sensitivity. Furthermore, sensitivity to agents in other chemotherapeutic classes (e.g., vinblastine and etoposide) also increased with the mutation of Pldn. In contrast, a mutation in another melanosomal regulatory gene, Hps1, minimally affects melanosome biogenesis, preserves the formation of mature melanosomes, and has no effect on cis-platin or vinblastine response. Together, these data provide the first direct evidence that melanosomal regulatory genes influence drug sensitivity and that the presence of mature melanosomes likely contributes to melanoma resistance to therapy. [Cancer Res 2009;69(3):992-9]

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Section: Discussionmentioning

confidence: 87%

Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes

et al. 2009

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“…Platinum was not detected in other sites, such as mitochondria, rough endoplasmic reticulum, Golgi complex, nuclear heterochromatin, nuclear matrix, and nucleolus [18]. Studies on cell cultures exposed to cisplatin have produced conflicting results [18]. In some circumstances, lack of detection of platinum deposits in the nucleus may have been related to the drug exposure schedule and = or drug concentrations used.…”

Section: Discussionmentioning

confidence: 94%

“…When platinum uracil blue was used, singlemembrane bound bodies named``platinosomes'' were detected. Platinum was not detected in other sites, such as mitochondria, rough endoplasmic reticulum, Golgi complex, nuclear heterochromatin, nuclear matrix, and nucleolus [18]. Studies on cell cultures exposed to cisplatin have produced conflicting results [18].…”

Section: Discussionmentioning

confidence: 96%

“…Previous electron microscopy studies have tried to address the tissue = cellular distribution of platinum after cisplatin exposure in an attempt to identify the cellular target of the drug. Ghadially et al showed that when cisplatin was injected into the rabbit knee joint, no platinum was found in any intracellular or extracellular compartment [17]. When platinum uracil blue was used, singlemembrane bound bodies named``platinosomes'' were detected.…”

Section: Discussionmentioning

confidence: 98%

“…Little and conflicting ultrastructural information is available on the intracellular distribution of platinum complexes [17,18]. Previous electron microscopy studies have tried to address the tissue = cellular distribution of platinum after cisplatin exposure in an attempt to identify the cellular target of the drug.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Electron Microscopy Analysis of Early Localization of Cisplatin in Ovarian Carcinoma Cells

Beretta

Righetti

Lombardi

et al. 2002

Ultrastructural Pathology

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Taking advantage of the electron-dense nature of platinum, in this study the authors used an electron microscopy approach to investigate the cellular localization of cisplatin in an ovarian carcinoma cell line. Platinum spots were detected in contact with the plasma membrane and the nuclear envelope as well as in the cytoplasm and nuclear matrices. Contact with the plasma membrane was through a single blunt contact or spanning through the membrane. No sequestration in intracellular vescicles was observed, thereby supporting that phagocytosis and receptor-mediated endocytosis were not occurring. A molecular analysis indicated lack of expression of aquaporin 9, thus excluding its involvement in the membrane translocation of cisplatin. The present data suggest that cisplatin rapidly accumulates in the cell through endocytosis-independent membrane translocation and are consistent with passive diffusion.

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Platinum Anticancer Drugs, Chemical Biology of

Zhang

Whan

Hambley

2008

Wiley Encyclopedia of Chemical Biology

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In the past, studies into the distribution of platinum anti‐cancer agents inside cancer cells were experimentally challenging because of a lack of readily available and sensitive platinum mapping techniques. Recent advancements in the area of platinum mapping in cells have meant that the biologic fate of cisplatin and its derivatives can be studied in several new ways. In particular, electron microscopy, fluorescence microscopy, and synchrotron radiation induced X‐ray emission have made significant contributions in the study of cisplatin in vitro . The applications of these three techniques and the insights they provide into the intracellular distributions and interactions platinum complexes are reviewed here. The strengths and weaknesses of each technique and their potentials for additional use in this field of research have been evaluated.

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Platinosomes produced in synovial membrane by platinum coordination complexes

Cited by 9 publications

References 8 publications

Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes

Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes

Electron Microscopy Analysis of Early Localization of Cisplatin in Ovarian Carcinoma Cells

Platinum Anticancer Drugs, Chemical Biology of

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