Apoptosis in ovarian granulosa cells of cattle: Morphological features and clearance by homologous phagocytosis

Carou, María Clara; Cruzans, Paula Romina; Maruri, Alejandro; Stockert, Juan C.; Lombardo, Daniel Marcelo

doi:10.1016/j.acthis.2014.11.006

Cited by 10 publications

(7 citation statements)

References 52 publications

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“…From the results, Artonin E-treated MCF-7 breast cancer cells displayed characteristic features of apoptosis,21,22 including the following: cell shrinkage, membrane alteration, DNA fragmentation, and nuclear condensation in a dose-dependent manner. These morphological characteristics of the breast cancer cells revealed the involvement of apoptosis.…”

Section: Discussionmentioning

confidence: 98%

Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells

Etti¹,

Abdullah²,

Hashim³

et al. 2017

DDDT

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Artonin E is a prenylated flavonoid compound isolated from the stem bark of Artocarpus elasticus. This phytochemical has been previously reported to be drug-like with full compliance to Lipinski’s rule of five and good physicochemical properties when compared with 95% of orally available drugs. It has also been shown to possess unique medicinal properties that can be utilized in view of alleviating most human disease conditions. In this study, we investigated the cytotoxic mechanism of Artonin E in MCF-7 breast cancer cells, which has so far not been reported. In this context, Artonin E significantly suppressed the breast cancer cell’s viability while inducing apoptosis in a dose-dependent manner. This apoptosis induction was caspase dependent, and it is mediated mainly through the intrinsic pathway with the elevation of total reactive oxygen species. Gene and protein expression studies revealed significant upregulation of cytochrome c, Bax, caspases 7 and 9, and p21 in Artonin E-treated MCF-7 cells, while MAPK and cyclin D were downregulated. Livin, a member of the inhibitors of apoptosis, whose upregulation has been noted to precede chemotherapeutic resistance and apoptosis evasion was remarkably repressed. In all, Artonin E stood high as a potential agent in the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 98%

Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells

Etti¹,

Abdullah²,

Hashim³

et al. 2017

DDDT

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show abstract

“…This was in accordance with a report by Carou et al . (2015)[ 32 ] and Gerl and Vaux (2005)[ 33 ], that apoptosis results in unique morphological changes like cell shrinkage, membrane alteration, DNA fragmentation and nuclear condensation. In fact, compounds that induce apoptosis are very essential in the management of cancer because evasion of apoptosis is implicated in cancer pathogenesis [ 28 ], [ 34 ] making its induction a strategy for cancer drug discovery[ 35 ].…”

Section: Discussionmentioning

confidence: 99%

The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells

et al. 2017

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Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.

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“…However, from the results of this study, Artonin E provoked morphological features typical of apoptosis in the Artonin E treated breast cancer cells. In support of this, Carou et al [15] and Gerl and Vaux [16], reported that apoptosis results in unique morphological changes including cell shrinkage, membrane alteration, DNA fragmentation and nuclear condensation. These features were observed in this study after treating the breast cancer cells with Artonin E. Succinctly, agents that trigger apoptosis are very essential in the management of cancer, giving that a unique hallmark of cancer cells is apoptosis evasion which is also implicated in its pathogenesis [17].…”

Section: Discussionmentioning

confidence: 80%

Apoptosis-Inducing Effect of Artonin E in Breast Cancer

Etti¹,

Abdullah²,

Kadir³

2018

Current Understanding of Apoptosis - Programmed Cell Death

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Breast cancer is among the principal cause of cancer fatalities in women. Notwithstanding the use of chemotherapy and advances in drug delivery techniques, cancer-related morbidity and mortality are still increasing with the increase in resistance to known therapeutics. This dilemma has drastically reduced the rate of survival from this deadly disease, creating a dire need for new drugs, especially from natural sources that would exhibit similar or better anticancer properties while imparting minimal adverse side effects. Among the bewildering hallmark capabilities of cancer is the evasion of apoptosis while in its course to immortality. Thus, induction of apoptosis in cancerous cells is an important breakthrough that cannot be ignored. There are, however, two major pathways of apoptosis in mammals, viz., the death receptor-mediated pathway (extrinsic pathway) and the mitochondrial-mediated pathway (intrinsic pathway). Artonin E, a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus, was seen to induce apoptosis in MCF-7 breast cancer cells, hence halting the breast cancer cells in their journey to immortality.

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Apoptosis in ovarian granulosa cells of cattle: Morphological features and clearance by homologous phagocytosis

Cited by 10 publications

References 52 publications

Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells

Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells

The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells

Apoptosis-Inducing Effect of Artonin E in Breast Cancer

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