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Sooncheol Ahn - One of the best experts on this subject based on the ideXlab platform.
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inhibition of autophagy promotes Salinomycin induced apoptosis via reactive oxygen species mediated pi3k akt mtor and erk p38 mapk dependent signaling in human prostate cancer cells
International Journal of Molecular Sciences, 2017Co-Authors: Kwangyoun Kim, Kwang Il Park, Sunghoon Kim, Sulgi Park, Young Woo Kim, Young Kyo Seo, Sooncheol AhnAbstract:Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether Salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells. Cell viability assay, Western blot, annexin V/propidium iodide assay, acridine orange (AO) staining, caspase-3 activity assay, reactive oxygen species (ROS) production, and mitochondrial membrane potential were assayed. Our data showed that Salinomycin alters the sensitivity of prostate cancer cells to autophagy. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, enhanced the Salinomycin-induced apoptosis. Notably, Salinomycin decreased phosphorylated of AKT and phosphorylated mammalian target of rapamycin (mTOR) in prostate cancer cells. Pretreatment with LY294002, an autophagy and PI3K inhibitor, enhanced the Salinomycin-induced apoptosis by decreasing the AKT and mTOR activities and suppressing autophagy. However, pretreatment with PD98059 and SB203580, an extracellular signal-regulated kinases (ERK), and p38 inhibitors, suppressed the Salinomycin-induced autophagy by reversing the upregulation of ERK and p38. In addition, pretreatment with N-acetyl-l-cysteine (NAC), an antioxidant, inhibited Salinomycin-induced autophagy by suppressing ROS production. Our results suggested that Salinomycin induces apoptosis, which was related to ROS-mediated autophagy through regulation of the PI3K/AKT/mTOR and ERK/p38 MAPK signaling pathways.
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Salinomycin induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization
Biochemical and Biophysical Research Communications, 2011Co-Authors: Kwangyoun Kim, Sooncheol Ahn, Sun Nyoung Yu, Sun Yi Lee, Sung Sik Chun, Yong Lark Choi, Yeong Min Park, Chungseog Song, Bandana ChatterjeeAbstract:The anticancer activity of Salinomycin has evoked excitement due to its recent identification as a selective inhibitor of breast cancer stem cells (CSCs) and its ability to reduce tumor growth and metastasis in vivo. In prostate cancer, similar to other cancer types, CSCs and/or progenitor cancer cells are believed to drive tumor recurrence and tumor growth. Thus Salinomycin can potentially interfere with the end-stage progression of hormone-indifferent and chemotherapy-resistant prostate cancer. Androgen-responsive (LNCaP) and androgen-refractive (PC-3, DU-145) human prostate cancer cells showed dose- and time-dependent reduced viability upon Salinomycin treatment; non-malignant RWPE-1 prostate cells were relatively less sensitive to drug-induced lethality. Salinomycin triggered apoptosis of PC-3 cells by elevating the intracellular ROS level, which was accompanied by decreased mitochondrial membrane potential, translocation of Bax protein to mitochondria, cytochrome c release to the cytoplasm, activation of the caspase-3 and cleavage of PARP-1, a caspase-3 substrate. Expression of the survival protein Bcl-2 declined. Pretreatment of PC-3 cells with the antioxidant N-acetylcysteine prevented escalation of oxidative stress, dissipation of the membrane polarity of mitochondria and changes in downstream molecular events. These results are the first to link elevated oxidative stress and mitochondrial membrane depolarization to Salinomycin-mediated apoptosis of prostate cancer cells.
Samir Attoub - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1
2016Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 mM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but no
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inhibitory effects of Salinomycin on cell survival colony growth migration and invasion of human non small cell lung cancer a549 and lnm35 involvement of nag 1
PLOS ONE, 2013Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 µM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but not cell survival. These findings identify Salinomycin as a promising novel therapeutic agent for lung cancer.
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Salinomycin induces apoptosis and senescence in breast cancer upregulation of p21 downregulation of survivin and histone h3 and h4 hyperacetylation
Biochimica et Biophysica Acta, 2013Co-Authors: Yusra Al Dhaheri, Kholoud Arafat, Samir Attoub, Synan Abuqamar, Ali H Eid, Nesreen Mohammed Al Faresi, Rabah IratniAbstract:Abstract Background In the present study, we investigated the effect of Salinomycin on the survival of three human breast cancer cell lines MCF-7, T47D and MDA-MB-231 grown in adherent culture conditions. Methods Cell viability was measured by CellTiter-Glo and Trypan blue exclusion assay. Apoptosis was determined by caspase 3/7 activation, PARP cleavage and Annexin V staining. Cell cycle distribution was assessed by propidium iodide flow cytometry. Senescence was confirmed by measuring the senescence-associated β-galactosidase activity. Changes in protein expression and histone hyperacetylation was determined by western blot and confirmed by immunofluorescence assay. Results Salinomycinwas able to inhibit the growth of the three cell lines in time- and concentration-dependent manners. We showed that depending on the concentrations used, Salinomycin elicits different effects on theMDA-MB-231 cells. High concentrations of Salinomycin induced a G2 arrest, downregulation of survivin and triggered apoptosis. Interestingly, treatment with low concentrations of Salinomycin induced a transient G1 arrest at earlier time point and G2 arrest at later point and senescence associatedwith enlarged cellmorphology, upregulation of p21 protein, increase in histone H3 and H4 hyperacetylation and expression of SA-β-Gal activity. Furthermore, we found that Salinomycin was able to potentiate the killing of the MCF-7 and MDA-MB-231 cells, by the chemotherapeutic agents, 4-Hydroxytamoxifen and frondoside A, respectively. Conclusion Our data are the first to link senescence and histone modifications to Salinomycin. Significance This study provides a new insight to better understand the mechanism of action of Salinomycin, at least in breast cancer cells.
Kholoud Arafat - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1
2016Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 mM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but no
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inhibitory effects of Salinomycin on cell survival colony growth migration and invasion of human non small cell lung cancer a549 and lnm35 involvement of nag 1
PLOS ONE, 2013Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 µM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but not cell survival. These findings identify Salinomycin as a promising novel therapeutic agent for lung cancer.
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Salinomycin induces apoptosis and senescence in breast cancer upregulation of p21 downregulation of survivin and histone h3 and h4 hyperacetylation
Biochimica et Biophysica Acta, 2013Co-Authors: Yusra Al Dhaheri, Kholoud Arafat, Samir Attoub, Synan Abuqamar, Ali H Eid, Nesreen Mohammed Al Faresi, Rabah IratniAbstract:Abstract Background In the present study, we investigated the effect of Salinomycin on the survival of three human breast cancer cell lines MCF-7, T47D and MDA-MB-231 grown in adherent culture conditions. Methods Cell viability was measured by CellTiter-Glo and Trypan blue exclusion assay. Apoptosis was determined by caspase 3/7 activation, PARP cleavage and Annexin V staining. Cell cycle distribution was assessed by propidium iodide flow cytometry. Senescence was confirmed by measuring the senescence-associated β-galactosidase activity. Changes in protein expression and histone hyperacetylation was determined by western blot and confirmed by immunofluorescence assay. Results Salinomycinwas able to inhibit the growth of the three cell lines in time- and concentration-dependent manners. We showed that depending on the concentrations used, Salinomycin elicits different effects on theMDA-MB-231 cells. High concentrations of Salinomycin induced a G2 arrest, downregulation of survivin and triggered apoptosis. Interestingly, treatment with low concentrations of Salinomycin induced a transient G1 arrest at earlier time point and G2 arrest at later point and senescence associatedwith enlarged cellmorphology, upregulation of p21 protein, increase in histone H3 and H4 hyperacetylation and expression of SA-β-Gal activity. Furthermore, we found that Salinomycin was able to potentiate the killing of the MCF-7 and MDA-MB-231 cells, by the chemotherapeutic agents, 4-Hydroxytamoxifen and frondoside A, respectively. Conclusion Our data are the first to link senescence and histone modifications to Salinomycin. Significance This study provides a new insight to better understand the mechanism of action of Salinomycin, at least in breast cancer cells.
Rabah Iratni - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1
2016Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 mM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but no
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inhibitory effects of Salinomycin on cell survival colony growth migration and invasion of human non small cell lung cancer a549 and lnm35 involvement of nag 1
PLOS ONE, 2013Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 µM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but not cell survival. These findings identify Salinomycin as a promising novel therapeutic agent for lung cancer.
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Salinomycin induces apoptosis and senescence in breast cancer upregulation of p21 downregulation of survivin and histone h3 and h4 hyperacetylation
Biochimica et Biophysica Acta, 2013Co-Authors: Yusra Al Dhaheri, Kholoud Arafat, Samir Attoub, Synan Abuqamar, Ali H Eid, Nesreen Mohammed Al Faresi, Rabah IratniAbstract:Abstract Background In the present study, we investigated the effect of Salinomycin on the survival of three human breast cancer cell lines MCF-7, T47D and MDA-MB-231 grown in adherent culture conditions. Methods Cell viability was measured by CellTiter-Glo and Trypan blue exclusion assay. Apoptosis was determined by caspase 3/7 activation, PARP cleavage and Annexin V staining. Cell cycle distribution was assessed by propidium iodide flow cytometry. Senescence was confirmed by measuring the senescence-associated β-galactosidase activity. Changes in protein expression and histone hyperacetylation was determined by western blot and confirmed by immunofluorescence assay. Results Salinomycinwas able to inhibit the growth of the three cell lines in time- and concentration-dependent manners. We showed that depending on the concentrations used, Salinomycin elicits different effects on theMDA-MB-231 cells. High concentrations of Salinomycin induced a G2 arrest, downregulation of survivin and triggered apoptosis. Interestingly, treatment with low concentrations of Salinomycin induced a transient G1 arrest at earlier time point and G2 arrest at later point and senescence associatedwith enlarged cellmorphology, upregulation of p21 protein, increase in histone H3 and H4 hyperacetylation and expression of SA-β-Gal activity. Furthermore, we found that Salinomycin was able to potentiate the killing of the MCF-7 and MDA-MB-231 cells, by the chemotherapeutic agents, 4-Hydroxytamoxifen and frondoside A, respectively. Conclusion Our data are the first to link senescence and histone modifications to Salinomycin. Significance This study provides a new insight to better understand the mechanism of action of Salinomycin, at least in breast cancer cells.
Yusra Al Dhaheri - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1
2016Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 mM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but no
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inhibitory effects of Salinomycin on cell survival colony growth migration and invasion of human non small cell lung cancer a549 and lnm35 involvement of nag 1
PLOS ONE, 2013Co-Authors: Kholoud Arafat, Rabah Iratni, Takashi Takahashi, Khatija Parekh, Yusra Al Dhaheri, Thomas E. Adrian, Samir AttoubAbstract:A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of Salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, Salinomycin (2.5–5 µM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, Salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that Salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but not cell survival. These findings identify Salinomycin as a promising novel therapeutic agent for lung cancer.
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Salinomycin induces apoptosis and senescence in breast cancer upregulation of p21 downregulation of survivin and histone h3 and h4 hyperacetylation
Biochimica et Biophysica Acta, 2013Co-Authors: Yusra Al Dhaheri, Kholoud Arafat, Samir Attoub, Synan Abuqamar, Ali H Eid, Nesreen Mohammed Al Faresi, Rabah IratniAbstract:Abstract Background In the present study, we investigated the effect of Salinomycin on the survival of three human breast cancer cell lines MCF-7, T47D and MDA-MB-231 grown in adherent culture conditions. Methods Cell viability was measured by CellTiter-Glo and Trypan blue exclusion assay. Apoptosis was determined by caspase 3/7 activation, PARP cleavage and Annexin V staining. Cell cycle distribution was assessed by propidium iodide flow cytometry. Senescence was confirmed by measuring the senescence-associated β-galactosidase activity. Changes in protein expression and histone hyperacetylation was determined by western blot and confirmed by immunofluorescence assay. Results Salinomycinwas able to inhibit the growth of the three cell lines in time- and concentration-dependent manners. We showed that depending on the concentrations used, Salinomycin elicits different effects on theMDA-MB-231 cells. High concentrations of Salinomycin induced a G2 arrest, downregulation of survivin and triggered apoptosis. Interestingly, treatment with low concentrations of Salinomycin induced a transient G1 arrest at earlier time point and G2 arrest at later point and senescence associatedwith enlarged cellmorphology, upregulation of p21 protein, increase in histone H3 and H4 hyperacetylation and expression of SA-β-Gal activity. Furthermore, we found that Salinomycin was able to potentiate the killing of the MCF-7 and MDA-MB-231 cells, by the chemotherapeutic agents, 4-Hydroxytamoxifen and frondoside A, respectively. Conclusion Our data are the first to link senescence and histone modifications to Salinomycin. Significance This study provides a new insight to better understand the mechanism of action of Salinomycin, at least in breast cancer cells.
