Silibinin-Induced Apoptosis in MCF7 and T47D Human Breast Carcinoma Cells Involves Caspase-8 Activation and Mitochondrial Pathway

Tiwari, Prabha; Kumar, Amit; Balakrishnan, S. A.; Kushwaha, H.S.; Mishra, Kaushala Prasad

doi:10.3109/07357907.2010.535053

Cited by 37 publications

(25 citation statements)

References 33 publications

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“…This indicates that other caspase mechanisms are involved in silibinininduced MCF7 cell death. These results are similar to reports that silibinin induces apoptosis through a mechanism independent of caspase-8 activation in MCF7 and T47D breast cancer cells (Tiwari et al, 2011).…”

Section: Discussionsupporting

confidence: 92%

Silibinin Induces Cell Death through Reactive Oxygen Species–Dependent Downregulation of Notch-1/ERK/Akt Signaling in Human Breast Cancer Cells

Kim

Woo

Kim

et al. 2014

J Pharmacol Exp Ther

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The present study was undertaken to determine the underlying mechanism of silibinin-induced cell death in human breast cancer cell lines MCF7 and MDA-MB-231. Silibinin-induced cell death was attenuated by antioxidants, N-acetylcysteine (NAC) and 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid, suggesting that the effect of silibinin was dependent on generation of reactive oxygen species (ROS). Western blot analysis showed that silibinin induced downregulation of extracellular signal-regulated kinase (ERK) and Akt. When cells were transiently transfected with constitutively active (ca) mitogen-activated protein kinase (MEK), an upstream kinase of ERK and caAkt, they showed resistance to silibinin-induced cell death. Silibinin decreased the cleavage of Notch-1 mRNA and protein levels. Notch-1-overexpressed cells were resistant to the silibinin-induced cell death. Inhibition of Notch-1 signaling was dependent on ROS generation. Overexpression of Notch-1 prevented silibinin-induced inhibition of ERK and Akt phosphorylation. Silibinin-induced cell death was accompanied by increased cleavage of caspase-3 and was prevented by caspase-3 inhibitor in MDA-MB-231 cells but not in MCF7 cells. Silibinin induced translocation of apoptosisinducing factor (AIF), which was blocked by NAC, and transfection of caMEK and caAkt. Silibinin-induced cell death was prevented by silencing of AIF expression using small interfering AIF RNA in MCF7 cells but not in MDA-MB-231 cells. In conclusion, silibinin induces cell death through an AIF-dependent mechanism in MCF7 cells and a caspase-3-dependent mechanism in MDA-MB-231 cells, and ROS generation and Notch-1 signaling act upstream of the ERK and Akt pathway. These data suggest that silibinin may serve as a potential agent for induction of apoptosis in human breast cancer cells.

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Section: Discussionsupporting

confidence: 92%

Silibinin Induces Cell Death through Reactive Oxygen Species–Dependent Downregulation of Notch-1/ERK/Akt Signaling in Human Breast Cancer Cells

Kim

Woo

Kim

et al. 2014

J Pharmacol Exp Ther

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“…Silymarin은 silibinin, siliychristin, silydianin 등의 입체 이성질체를 포함하고 있으며, 현재까지 전립선암, 폐암, 대장 암, 피부암, 방광암, 유방암 등 다양한 암세포에 대하여 항암 효과가 있다고 보고되어 있다 [1][2]6,[8][9]19,21,26,29,[30][31][33][34]. 특히 silibinin은 urokinase plasminogen activator (u-PA), matrix metalloproteinase-2 (MMP-2), mitogen-activated protein kinase (MAPK)의 활성을 조절하여 암세포의 증식, 침윤 및 전이에 영향을 미치고 [4][5], 세포주기조절 및 세포사멸 유 도에 관한 활성이 보고되어 있다 [7,11,[17][18]25,28].…”

Section: 서 론unclassified

Silibinin Inhibits Cell Growth and Induces Apoptosis through Cell-cycle Arrest in PC-3 Prostate Cancer Cells

김상헌

김광연²,

유선녕³

et al. 2011

Journal of Life Science

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“…In a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, silibinin inhibits tumor growth, progression, local invasion and distant metastasis [56]. Silibinin induces both death receptor-mediated and mitochondrial-mediated apoptosis in human breast cancer MCF-7 cells [58]. Silibinin also reduces hepatocellular carcinoma xenograft growth through the inhibition of cell proliferation, cell cycle progression, as well as phosphatase and tensin homolog/P-Akt and extracellular signal-regulated kinase (ERK) signaling.…”

Section: Introductionmentioning

confidence: 99%

Anti-cancer natural products isolated from chinese medicinal herbs

et al. 2011

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In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin), alkaloids (berberine), terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid), quinones (shikonin and emodin) and saponins (ginsenoside Rg3), which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

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Silibinin-Induced Apoptosis in MCF7 and T47D Human Breast Carcinoma Cells Involves Caspase-8 Activation and Mitochondrial Pathway

Cited by 37 publications

References 33 publications

Silibinin Induces Cell Death through Reactive Oxygen Species–Dependent Downregulation of Notch-1/ERK/Akt Signaling in Human Breast Cancer Cells

Silibinin Induces Cell Death through Reactive Oxygen Species–Dependent Downregulation of Notch-1/ERK/Akt Signaling in Human Breast Cancer Cells

Silibinin Inhibits Cell Growth and Induces Apoptosis through Cell-cycle Arrest in PC-3 Prostate Cancer Cells

Anti-cancer natural products isolated from chinese medicinal herbs

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