Induction of G1-phase cell cycle arrest and apoptosis pathway in MDA-MB-231 human breast cancer cells by sulfated polysaccharide extracted from Laurencia papillosa

Murad, Hossam; Hawat, Mohammad; Ekhtiar, Adnan; Aljapawe, Abdulmunim; Abbas, Assef; Darwish, H D; Sbenati, Oula; Ghannam, Ahmed

doi:10.1186/s12935-016-0315-4

Cited by 131 publications

(85 citation statements)

References 61 publications

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“…In 4T1.2 mammary tumor cells, administration of A77636 elevated the level of cleaved caspase 3 as a marker of apoptosis12, as well as the level of LC3-phosphatidylethanolamine conjugate (LC3II) as an autophagosome marker13. We have previously reported that salubrinal is capable of inducing cellular death of 4T1 cells as well as MDA-MB-231 cells by elevating p-eIF2α14.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Minami¹,

Liu²,

Liu³

et al. 2017

Sci Rep

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Dopaminergic signaling plays a critical role in the nervous system, but little is known about its potential role in breast cancer and bone metabolism. A screening of ~1,000 biologically active compounds revealed that a selective agonist of dopamine receptor D1 (DRD1), A77636, inhibited proliferation of 4T1.2 mammary tumor cells as well as MDA-MB-231 breast cancer cells. Herein, we examined the effect of A77636 on bone quality using a mouse model of bone metastasis from mammary tumor. A77636 inhibited migration of cancer cells in a DRD1-dependent fashion and suppressed development of bone-resorbing osteoclasts by downregulating NFATc1 through the elevation of phosphorylation of eIF2α. In the mouse model of bone metastasis, A77636 reduced osteolytic lesions and prevented mechanical weakening of the femur and tibia. Collectively, we expect that dopaminergic signaling might provide a novel therapeutic target for breast cancer and bone metastasis.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Minami¹,

Liu²,

Liu³

et al. 2017

Sci Rep

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“…Protein Bcl-2 plays a key role in the regulation of apoptosis in which an increasing Bax/Bcl-2 ratio enhances caspase-3 activity and subsequently induces apoptosis in tumor cells [50]. Phytochemicals seem to have an important regulatory role in Bax/Bcl-2/caspase-3 signaling in breast carcinogenesis [51,52]. In this study, cinnamon caused a significant increase in the Bax/Bcl-2 ratio, which correlated with an increase in caspase-3 expression in treated mammary tumors in rats.…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

et al. 2020

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Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and α-terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters—ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.

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“…An in vitro study revealed that sulfated polysaccharide ASPE extracted from Laurencia papillosa inhibits the proliferation of MDA-MB-231 human breast cancer cells by inhibiting the ratio of ROS and Bax/Bcl-2 protein levels in cells (Table 2) [90]. Moreover, carrageenans from the same source inhibited the proliferation and cell viability of MCF-7 human breast cancer cells by the same route in a dose-dependent manner (Table 2) [92].…”

Section: Red Algal Polysaccharidesmentioning

confidence: 99%

The Antioxidant Activity of Polysaccharides Derived from Marine Organisms: An Overview

et al. 2019

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Marine-derived antioxidant polysaccharides have aroused extensive attention because of their potential nutritional and therapeutic benefits. However, the comprehensive comparison of identified marine-derived antioxidant polysaccharides is still inaccessible, which would facilitate the discovery of more efficient antioxidants from marine organisms. Thus, this review summarizes the sources, chemical composition, structural characteristics, and antioxidant capacity of marine antioxidant polysaccharides, as well as their protective in vivo effects mediated by antioxidative stress reported in the last few years (2013–2019), and especially highlights the dominant role of marine algae as antioxidant polysaccharide source. In addition, the relationships between the chemical composition and structural characteristics of marine antioxidant polysaccharides with their antioxidant capacity were also discussed. The antioxidant activity was found to be determined by multiple factors, including molecular weight, monosaccharide composition, sulfate position and its degree.

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Induction of G1-phase cell cycle arrest and apoptosis pathway in MDA-MB-231 human breast cancer cells by sulfated polysaccharide extracted from Laurencia papillosa

Cited by 131 publications

References 61 publications

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

The Antioxidant Activity of Polysaccharides Derived from Marine Organisms: An Overview

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