Cytofluorescence Localization of Adriamycin-Binding Sites of Cardiac Tissue

Malignant melanoma is one the most aggressive types of cancer and its incidence has gradually increased in the last years, accounting for about 75% of skin cancer deaths. This poor prognosis results from the tumor resistance to conventional drugs mainly by deregulation of apoptotic pathways. The aim of this work was to investigate the cell death mechanism induced by α-pinene and its therapeutic application. Our results demonstrated that α-pinene was able to induce apoptosis evidenced by early disruption of the mitochondrial potential, production of reactive oxygen species, increase in caspase-3 activity, heterochromatin aggregation, DNA fragmentation and exposure of phosphatidyl serine on the cell surface. Most importantly, this molecule was very effective in the treatment of experimental metastatic melanoma reducing the number of lung tumor nodules. This is the first report on the apoptotic and antimetastatic activity of isolated α-pinene.

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“…Cells were observed by fluorescence microscopy. Apoptotic cells were detected by chromatin condensation [14].…”

Section: Chromatin Condensation Analysismentioning

confidence: 99%

α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model

Matsuo

Figueiredo

Arruda

et al. 2011

Biochemical and Biophysical Research Communications

164

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“…The persistence of doxorubicin within myocardial cells had been previously demonstrated by the early histofluorescence study by Amin et al [16]. Following the intravenous administration of doxorubicin at a dose of 15 mg kg −1 to Sprague Dawley rats, fluorescence emission was observed in myocardial cells of the left ventricle until 28 days after administration.…”

Section: Accumulation Of Doxorubicin Within the Heartmentioning

confidence: 76%

The cardioprotective effect of dexrazoxane (Cardioxane) is consistent with sequestration of poly(ADP-ribose) by self-assembly and not depletion of topoisomerase 2B

McCormack¹

2018

ecancer

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Following systematic scrutiny of the evidence in support of the hypothesis that the cardioprotective mechanism of action of dexrazoxane is mediated by a ‘depletion’ or ‘downregulation’ of Top2β protein levels in heart tissue, the author concludes that this hypothesis is untenable. In seeking to understand how dexrazoxane protects the heart, the outcomes of a customised association rule learning algorithm incorporating the use of antecedent surrogate variables (CEME, 2017 McCormack Pharma) reveal a previously unknown relationship between dexrazoxane and poly(ADP-ribose) (PAR) polymer. The author shows how this previously unknown relationship explains both acute and long-term cardioprotection in patients receiving anthracyclines. In addition, as a direct inhibitor of PAR dexrazoxane has access to the epigenome and this offers a new insight into protection by dexrazoxane against doxorubicin-induced late-onset damage [McCormack K, manuscript in preparation]. Notably, through this review article, the author illustrates the practical application of probing natural language text using an association rule learning algorithm for the discovery of new and interesting associations that, otherwise, would remain lost. Historically, the use of CEME enabled the first report of the capacity of a small molecule to catalyse the hybrid self-assembly of a nucleic acid biopolymer via canonical and non-canonical, non-covalent interactions analogous to Watson Crick and Hoogsteen base pairing, respectively.

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