Abstract
Indole-3-carbinol (I3C) and its oligomeric derivatives have been widely studied for their chemopreventive and chemotherapeutic properties. We have previously shown that the I3C cyclic tetrameric derivative CTet inhibits breast cancer cell proliferation in vitro and in xenotrasplanted tumor. Here we report the antitumoral activity of a mixture of tri- and tetrameric cyclic I3C derivatives (CTr/CTet) both in vitro (MCF-7 and MDA-MB-231 breast cancer cell lines) and in vivo in a tumor xenograft model. CTr/CTet mixture avoids the low solubility drawbacks of CTet, thus favouring its solubilization, and reducing purification process, time and costs. CTr/CTet mixture has been shown to inhibit breast cancer cell proliferation (IC50 = 1.3 and 1.6 μg/ml in MCF-7 and MDAMB- 231, respectively) inducing the G0/1 cell cycle phase accumulation. The main molecular events related to CTr/CTet activity are the overexpression of p21, p27 and GADD45A, nuclear translocation of FOXO3a, inhibition of Akt activity and downregulation of estrogen receptor. In vivo, the growth of xenotransplanted tumor has been inhibited and the pro-tumoral low molecular weight cyclin E downregulation has been detected. Our data indicate that CTr/CTet is a potential anticancer combination agent for both hormoneresponsive and triple-negative breast tumors.
Keywords: Akt, Breast Cancer, FOXO3a, GADD45A, I3C cyclic derivatives, LMW cyclin E, CTr/CTet, p21/CDKN1A, p27/CDKN1B
Anti-Cancer Agents in Medicinal Chemistry
Title:Antitumoral Activity of Indole-3-carbinol Cyclic tri- and Tetrameric Derivatives Mixture in Human Breast Cancer Cells: In Vitro and In Vivo Studies
Volume: 13 Issue: 4
Author(s): Giorgio Brandi, Alessandra Fraternale, Simone Lucarini, Mirko Paiardini, Mauro De Santi, Barbara Cervasi, Maria F. Paoletti, Luca Galluzzi, Andrea Duranti and Mauro Magnani
Affiliation:
Keywords: Akt, Breast Cancer, FOXO3a, GADD45A, I3C cyclic derivatives, LMW cyclin E, CTr/CTet, p21/CDKN1A, p27/CDKN1B
Abstract: Indole-3-carbinol (I3C) and its oligomeric derivatives have been widely studied for their chemopreventive and chemotherapeutic properties. We have previously shown that the I3C cyclic tetrameric derivative CTet inhibits breast cancer cell proliferation in vitro and in xenotrasplanted tumor. Here we report the antitumoral activity of a mixture of tri- and tetrameric cyclic I3C derivatives (CTr/CTet) both in vitro (MCF-7 and MDA-MB-231 breast cancer cell lines) and in vivo in a tumor xenograft model. CTr/CTet mixture avoids the low solubility drawbacks of CTet, thus favouring its solubilization, and reducing purification process, time and costs. CTr/CTet mixture has been shown to inhibit breast cancer cell proliferation (IC50 = 1.3 and 1.6 μg/ml in MCF-7 and MDAMB- 231, respectively) inducing the G0/1 cell cycle phase accumulation. The main molecular events related to CTr/CTet activity are the overexpression of p21, p27 and GADD45A, nuclear translocation of FOXO3a, inhibition of Akt activity and downregulation of estrogen receptor. In vivo, the growth of xenotransplanted tumor has been inhibited and the pro-tumoral low molecular weight cyclin E downregulation has been detected. Our data indicate that CTr/CTet is a potential anticancer combination agent for both hormoneresponsive and triple-negative breast tumors.
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Brandi Giorgio, Fraternale Alessandra, Lucarini Simone, Paiardini Mirko, De Santi Mauro, Cervasi Barbara, F. Paoletti Maria, Galluzzi Luca, Duranti Andrea and Magnani Mauro, Antitumoral Activity of Indole-3-carbinol Cyclic tri- and Tetrameric Derivatives Mixture in Human Breast Cancer Cells: In Vitro and In Vivo Studies, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (4) . https://dx.doi.org/10.2174/1871520611313040014
DOI https://dx.doi.org/10.2174/1871520611313040014 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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