Role of Nongenomic Activation of Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase/Extracellular Signal-Regulated Kinase 1/2 Pathways in 1,25D3-Mediated Apoptosis in Squamous Cell Carcinoma Cells

Ma, Yingyu; Yu, Weidong; Kong, Rui-Xian; Trump, Donald L.; Johnson, Candace S.

doi:10.1158/0008-5472.can-06-1333

Cited by 47 publications

(37 citation statements)

References 40 publications

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“…14,15 Little or no apoptosis is induced by 1,25D 3 in SCC cells when the entire population is assessed. 14,16 In the fraction of floating SCC cells following 1,25D 3 treatment, apoptosis can be detected, 17 suggesting that the floating cells account for a small part of the whole population. The ability of inecalcitol to induce apoptosis appears to be cell type-specific.…”

Section: Discussionmentioning

confidence: 99%

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Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Hidalgo

et al. 2013

Cell Cycle

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Section: Discussionmentioning

confidence: 99%

“…SCC and SCC-DR cells were collected and stained with PE-conjugated annexin V and 7AAD, according to manufacturer's instructions, as described previously. 16 Caspase activity assays. The activities of caspases-3, 8, 9 (R&D Systems) and caspase 10 (EMD Millipore) were measured using the caspase fluorometric assay kit following the manufacturer's protocols.…”

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confidence: 99%

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Hidalgo

et al. 2013

Cell Cycle

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“…The pro-apoptotic effect of wogonin was found to be mediated via activation of ERKs and caspases and is correlated with interruption of the PI3K/Akt/survivin signaling pathways in MCF-7 cells (20). A number of studies have shown the importance of ERK signaling in the regulation of apoptosis (26,27). Although the ERK pathway delivers a survival signal, studies using chemopreventive and chemotherapeutic agents have linked activation of ERKs with induction of apoptosis (28,29).…”

Section: Discussionmentioning

confidence: 99%

Chelidonium majus L. extract induces apoptosis through caspase activity via MAPK-independent NF-κB signaling in human epidermoid carcinoma A431 cells

Park

Kim

et al. 2014

Oncology Reports

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Abstract. Chelidonium majus L. (C. majus L.) is known to possess certain biological properties such as anti-inflammatory, antimicrobial, antiviral and antitumor activities. We investigated the effects of C. majus L. extract on human epidermoid carcinoma A431 cells through multiple mechanisms, including induction of cell cycle arrest, activation of the caspase-dependent pathway, blocking of nuclear factor-κB (NF-κB) activation and involvement in the mitogen-activated protein kinase (MAPK) pathway. C. majus L. inhibited the proliferation of A431 cells in a dose-and time-dependent manner, increased the percentage of apoptotic cells, significantly decreased the mRNA levels of cyclin D1, Bcl-2, Mcl-1 and survivin and increased p21 and Bax expression. Exposure of A431 cells to C. majus L. extract enhanced the activities of caspase-3 and caspase-9, while co-treatment with C. majus L., the pancaspase inhibitor Z-VAD-FMK and the caspase-3 inhibitor Z-DEVE-FMK increased the proliferation of A431 cells. C. majus L. extract not only inhibited NF-κB activation, but it also activated p38 MAPK and MEK/ERK signaling. Taken together, these results demonstrate that C. majus L. extract inhibits the proliferation of human epidermoid carcinoma A431 cells by inducing apoptosis through caspase activation and NF-κB inhibition via MAPK-independent pathway. IntroductionChelidonium majus is commonly known as greater celandine. It belongs to the family Papaveraceae and is widely distributed in Europe and western Asia. Extracts of Chelidonium majus L.(C. majus L.) have been shown to exhibit a variety of biological effects including anti-inflammatory, antimicrobial, antiviral and antitumor activities (1,2). The antitumor, antigenotoxic and hepatoprotective effects of C. majus L. extract suggest that it may be potentially useful as an anticancer therapeutic agent (3).Apoptosis is mediated through at least 3 major pathways, which are regulated by death receptors, mitochondria and the endoplasmic reticulum. Activation of the apoptosis pathway is a key mechanism by which cytotoxic drugs kill tumor cells. Defects in apoptosis signaling contribute to the drug resistance of tumor cells (4,5). The Bcl-2 family consists of important apoptotic regulators of programmed cell death. This family of proteins includes both anti-apoptotic molecules such as Bcl-2 and pro-apoptotic molecules such as Bax (6). Bcl-2 and Bcl-X L are members of the Bcl-2 family and are regulated by nuclear factor-(NF)-κB. These proteins can prevent release of cytochrome c and activation of caspases (7).Mitogen-activated protein kinase (MAPK) cascades are involved in the signaling pathways that regulate various cellular responses such as inflammation, proliferation and cell death (8). Three major mammalian MAPK subfamilies have been described: extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases and p38 kinases. Each MAPK is activated through a specific phosphorylation cascade (9,10). The ERK cascade is activated through receptor-mediated signaling stimuli and is...

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“…Cells were stained with Annexin V-PE and 7-AAD according to the manufacturer's instructions (BD Pharmingen). 14 The data was analysed using Winlist TM program (Verity House, Topsham, ME).…”

Section: Methodsmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11][12][13][14] Calcitriol has also been shown to reduce angiogenesis in a number of cancer models, which also contributes to the antitumor effect of calcitriol in vivo. 2 …”

Section: Introductionmentioning

confidence: 99%

Calcitriol enhances gemcitabine antitumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system

Flynn

et al. 2010

Cell Cycle

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Role of Nongenomic Activation of Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase/Extracellular Signal-Regulated Kinase 1/2 Pathways in 1,25D3-Mediated Apoptosis in Squamous Cell Carcinoma Cells

Abstract: Vitamin D is a steroid hormone that regulates calcium homeostasis and bone metabolism. The active form of vitamin D [1A,25-dihydroxyvitamin D 3 (1,25D3)] acts through both genomic and nongenomic pathways.

Cited by 47 publications

References 40 publications

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Chelidonium majus L. extract induces apoptosis through caspase activity via MAPK-independent NF-κB signaling in human epidermoid carcinoma A431 cells

Calcitriol enhances gemcitabine antitumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system

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