Andrographolide, a Novel NF-<i>κ</i>B Inhibitor, Induces Vascular Smooth Muscle Cell Apoptosis via a Ceramide-p47phox-ROS Signaling Cascade

Chen, Yu Ying; Hsu, Ming Jen; Sheu, Joen Rong; Lee, Lin Wen; Hsieh, Cheng Ying

doi:10.1155/2013/821813

Cited by 35 publications

(25 citation statements)

References 54 publications

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“…Apoptosis, the planned cell death, plays key roles in several physiologic processes in cell development (Chen et al, 2013). Failure in apoptosis leads to tumor growth and development as well as resistance to most oncologic therapies (Lowe et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

Gao

Wu²,

Zeng³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo (ARM) family, which has one or two ARM repeat domains as opposed to more than six-thirteen repeats in the classical Armadillo family members. Materials and Methods: In the study, we explore the biological functions of ALEX1 in breast cancer cells. Overexpression of ALEX1 and silencing of ALEX1 were performed with SK-BR3 and MCF-7 cell lines. Cell proliferation and colony formation assays, along with flow cytometry, were carried out to evaluate the roles of ALEX1. Results: ALEX1 overexpression in SK-BR3 breast cancer cells inhibited proliferation and induced apoptosis. Furthermore, depletion of ALEX1 in MCF-7 breast cancer cells increased proliferation and inhibited apoptosis. Additional analyses demonstrated that the overexpression of ALEX1 activated the intrinsic apoptosis cascades through up-regulating the expression of Bax, cytosol cytochrome c, active caspase-9 and active caspase-3 and down-regulating the levels of Bcl-2 and mitochondria cytochrome c. Simultaneouly, silencing of ALEX1 inhibited intrinsic apoptosis cascades through down-regulating the expression of Bax, cytosol cytochrome c, active caspase-9, and active caspase-3 and up-regulating the level of Bcl-2 and mitochondria cytochrome c. Conclusions: Our data suggest that ALEX1 as a crucial tumor suppressor gene has been involved in cell proliferation and apoptosis in breast cancer, which may serve as a novel candidate therapeutic target.

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Section: Discussionmentioning

confidence: 99%

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

Gao

Wu²,

Zeng³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…For instance, andrographolide, an NF- κ B inhibitor derived from the leaves of Andrographis paniculata , induces apoptosis through generation of ROS. 34 , 35 Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is an in-tracellular ROS producer. NOX is a complex composed of membrane-bound (p22phox and NOX 1-4) and cytoplasmic (Rac, p47phox, and p67phox) subunits.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 Inhibits Constitutive Activation of NF-κB Signaling in Human Breast Cancer (MDA-MB-231) Cells: ERK and Akt as Potential Upstream Targets

Kim¹,

Kim²,

Park³

et al. 2014

J Cancer Prev

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Ginsenoside Rg3, one of the major ingredients of heat-processed ginseng, has been reported to inhibit the growth of various cancer cells. We previously reported that Rg3 inhibited the proliferation and induced apoptosis of breast cancer (MDA-MB-231) cells. In the present study, we have explored the mechanism underlying the anti-proliferative and proapoptotic effects of Rg3 in MDA-MB-231 cells, which have constitutively activated NF-κB and the mutant form of p53. Rg3 inhibited DNA binding and transcriptional activity of NF-κB and these effects were attributable to its suppression of IKKβ activity, degradation of IκBα and subsequent nuclear translocation of the p65 subunit of NF-κB. Similarly, the constitutive activation of ERK and Akt through phosphorylation was gradually reduced in MDA-MB-231 cells treated with Rg3. The pharmacological inhibitors of these kinases both U0126 (MEK1/2 inhibitor) and LY294002 (PI3K inhibitor) abrogated the NF-κB DNA binding activity in MDA-MB-231 cells. In addition, Rg3 treatment lowered the levels of the mutant p53 in concentration- and time-dependent manners. Rg3 also increased the association between p53 and its negative regulator Mdm2 in MDA-MB-231 cells. These findings suggest that Rg3 induced apoptosis in MDA-MB-231 cells, which is mediated by blocking NF-κB signaling via inactivation of ERK and Akt as well as destabilization of mutant p53.

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“…Furthermore, the reduction of the inactive proenzyme form of caspase-3 and cleavage of PARP were also observed in the present study, indicating that it was a caspase-dependent apoptosis. A recent study also revealed that AP 1 induced vascular smooth muscle cell apoptosis via ceramide-p47phox-ROS and caspase-3 signaling cascade [46]. Notably, the intensities of the cleaved active forms of caspase-3 bands (17/19-kD) were very weak (data not shown).…”

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confidence: 82%

Andrographis paniculata Extracts and Major Constituent Diterpenoids Inhibit Growth of Intrahepatic Cholangiocarcinoma Cells by Inducing Cell Cycle Arrest and Apoptosis

et al. 2014

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Andrographis paniculata is an important herbal medicine widely used in several Asian countries for the treatment of various diseases due to its broad range of pharmacological activities. The present study reports that A. paniculata extracts potently inhibit the growth of liver (HepG2 and SK-Hep1) and bile duct (HuCCA-1 and RMCCA-1) cancer cells. A. paniculata extracts with different contents of major diterpenoids, including andrographolide, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and 14-deoxyandrographolide, exhibited a different potency of growth inhibition. The ethanolic extract of A. paniculata at the first true leaf stage, which contained a high amount of 14-deoxyandrographolide but a low amount of andrographolide, showed a cytotoxic effect to cancer cells about 4 times higher than the water extract of A. paniculata at the mature leaf stage, which contained a high amount of andrographolide but a low amount of 14-deoxyandrographolide. Andrographolide, not 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, or 14-deoxyandrographolide, possessed potent cytotoxic activity against the growth of liver and bile duct cancer cells. The cytotoxic effect of the water extract of A. paniculata at the mature leaf stage could be explained by the present amount of andrographolide, while the cytotoxic effect of the ethanolic extract of A. paniculata at the first true leaf stage could not. HuCCA-1 cells showed more sensitivity to A. paniculata extracts and andrographolide than RMCCA-1 cells. Furthermore, the ethanolic extract of A. paniculata at the first true leaf stage increased cell cycle arrest at the G0/G1 and G2/M phases, and induced apoptosis in both HuCCA-1 and RMCCA-1 cells. The expressions of cyclin-D1, Bcl-2, and the inactive proenzyme form of caspase-3 were reduced by the ethanolic extract of A. paniculata in the first true leaf stage treatment, while a proapoptotic protein Bax was increased. The cleavage of poly (ADP-ribose) polymerase was also found in the ethanolic extract of A. paniculata in the first true leaf stage treatment. This study suggests that A. paniculata could be a promising herbal plant for the alternative treatment of intrahepatic cholangiocarcinoma.

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Andrographolide, a Novel NF-κB Inhibitor, Induces Vascular Smooth Muscle Cell Apoptosis via a Ceramide-p47phox-ROS Signaling Cascade

Cited by 35 publications

References 54 publications

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

Ginsenoside Rg3 Inhibits Constitutive Activation of NF-κB Signaling in Human Breast Cancer (MDA-MB-231) Cells: ERK and Akt as Potential Upstream Targets

Andrographis paniculata Extracts and Major Constituent Diterpenoids Inhibit Growth of Intrahepatic Cholangiocarcinoma Cells by Inducing Cell Cycle Arrest and Apoptosis

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