Differential Cytostatic and Cytotoxic Action of Metallocorroles against Human Cancer Cells: Potential Platforms for Anticancer Drug Development

A gallium(III)-substituted amphiphilic corrole noncovalently associated with a targeting protein was previously found by us to confer promising cytotoxic and antitumor activities against a breast cancer cell line and a mouse xenograft breast cancer model. To further explore potential anticancer applications, the cytostatic and cytotoxic properties of six nontargeted metallocorroles were evaluated against seven human cancer cell lines. Results indicated that toxicity toward human cancer cells depended on the metal ion as well as corrole functional group substitution. Ga(III)-substituted metallocorrole 1-Ga inhibited proliferation of breast (MDA-MB-231), melanoma (SK-MEL-28), and ovarian (OVCAR-3) cancer cells primarily by arrest of DNA replication, whereas 2-Mn displayed both cytostatic and cytotoxic properties. Confocal microscopy revealed extensive uptake of 1-Ga into the cytoplasm of melanoma and ovarian cancer cells, while prostate cancer cells (DU-145) displayed extensive nuclear localization. The localization of 1-Ga to the nucleus in DU-145 cells was exploited to achieve a 3-fold enhancement in the IC_(50) of doxorubicin upon coadministration. Time–course studies showed that over 90% of melanoma cells incubated with 30 μM 1-Ga internalized metallocorrole after 15 min. Cellular uptake of 1-Ga and 1-Al was fastest and most efficient in melanoma, followed by prostate and ovarian cancer cells. Cell cycle analyses revealed that bis-sulfonated corroles containing Al(III), Ga(III), and Mn(III) induced late M phase arrest in several different cancer cell lines, a feature that could be developed for potential therapeutic benefit

The Influence of Chemical Structure and the Presence of Ascorbic Acid on Anthocyanins Stability and Spectral Properties in Purified Model Systems

The loss of color pigment is an important quality factor of food products. This work aimed to systematically study, in purified model systems, the influence of anthocyanins’ structure (by increasing the size of the conjugated sugar) and the presence of ascorbic acid on their stability and spectral properties during storage at two pH levels relevant to medium and high acid foods (6.5 and 4.5, respectively). Anthocyanins (cyanidin (Cy), cyanidin 3-O-β-glucoside (Cy3G) and cyanidin 3-O-β-rutinoside (Cy3R)) displayed first-order degradation rates, presenting higher stability in acidic medium and enhanced stability with increasing size of conjugated sugar. The addition of ascorbic acid resulted in significantly enhanced degradation. Changes in ultra violet visible (UV-VIS) spectral properties presented a decrease in typical color intensity and pointed towards formation of degradation products. Identification and kinetics of formation for cyanidin degradation products were obtained by high performance liquid chromatography system-mass spectrometry (HPLC-MS)

Differential Cytostatic and Cytotoxic Action of Metallocorroles against Human Cancer Cells: Potential Platforms for Anticancer Drug Development

A gallium­(III)-substituted amphiphilic corrole noncovalently associated with a targeting protein was previously found by us to confer promising cytotoxic and antitumor activities against a breast cancer cell line and a mouse xenograft breast cancer model. To further explore potential anticancer applications, the cytostatic and cytotoxic properties of six nontargeted metallocorroles were evaluated against seven human cancer cell lines. Results indicated that toxicity toward human cancer cells depended on the metal ion as well as corrole functional group substitution. Ga­(III)-substituted metallocorrole <b>1</b>-Ga inhibited proliferation of breast (MDA-MB-231), melanoma (SK-MEL-28), and ovarian (OVCAR-3) cancer cells primarily by arrest of DNA replication, whereas <b>2</b>-Mn displayed both cytostatic and cytotoxic properties. Confocal microscopy revealed extensive uptake of <b>1</b>-Ga into the cytoplasm of melanoma and ovarian cancer cells, while prostate cancer cells (DU-145) displayed extensive nuclear localization. The localization of <b>1</b>-Ga to the nucleus in DU-145 cells was exploited to achieve a 3-fold enhancement in the IC₅₀ of doxorubicin upon coadministration. Time–course studies showed that over 90% of melanoma cells incubated with 30 μM <b>1</b>-Ga internalized metallocorrole after 15 min. Cellular uptake of <b>1</b>-Ga and <b>1</b>-Al was fastest and most efficient in melanoma, followed by prostate and ovarian cancer cells. Cell cycle analyses revealed that bis-sulfonated corroles containing Al­(III), Ga­(III), and Mn­(III) induced late M phase arrest in several different cancer cell lines, a feature that could be developed for potential therapeutic benefit