Distinct Pro-Apoptotic Properties of Zhejiang Saffron against Human Lung Cancer Via a Caspase-8-9-3 Cascade

Liu, Dandan; Ye, Yilu; Zhang, Jing; Xu, Jiani; Qian, Xiao-Dong; Zhang, Qi

doi:10.7314/apjcp.2014.15.15.6075

Cited by 23 publications

(19 citation statements)

References 19 publications

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“…Crocin has been shown to induce apoptosis in tumor cells by down-regulating the expression of Bcl-2, survivin, cyclin D1 and up-regulating the expression of Bax in BALB/c xenograft tumor15. Distinct pro-apoptotic properties of crocin in human lung cancer were shown to act via the caspase-8-9-3 cascade16. A similar observation was made in apoptosis through the activation of caspases and enhancement of the Bax/Bcl-2 ratio in human gastric adenocarcinoma17.…”

mentioning

confidence: 66%

Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells

Hire

Srivastava

Davis

et al. 2017

Sci Rep

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Crocin, a component of saffron spice, is known to have an anticancer activity. However, the targets of crocin are not known. In this study, crocin was found to inhibit the proliferation of HCC70, HCC1806, HeLa and CCD1059sk cells by targeting microtubules. Crocin depolymerized both the interphase and mitotic microtubules of different cancer cells, inhibited mitosis and induced multipolar spindle formation in these cells. In vitro, crocin inhibited the assembly of pure tubulin as well as the assembly of microtubule-associated protein rich tubulin. Electron microscopic analysis showed that crocin inhibited microtubule assembly while it induced aggregation of tubulin at higher concentrations. Crocin co-eluted with tubulin suggesting that it binds to tubulin. Vinblastine inhibited the binding of crocin to tubulin while podophyllotoxin did not inhibit the crocin binding indicating that crocin binds at the vinblastine site on tubulin. The results suggested that crocin inhibited cell proliferation mainly by disrupting the microtubule network.

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confidence: 66%

Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells

Hire

Srivastava

Davis

et al. 2017

Sci Rep

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“…The cells were then incubated for 0, 6, 24 and 48 h and harvested, washed and resuspended in 25 µl of 10 µM substrate solution (PhiPhiLux and CaspaLux kit; OncoImmunin, Inc., Gaithersburg, MD, USA) before being incubated at 37˚C for 60 min. The cells were washed again in PBS and were analyzed by flow cytometry as described previously (16,18,19).…”

Section: Reactive Oxygen Species (Ros) Intracellular Camentioning

confidence: 99%

“…Cells (2x10 6 / dish) were treated with 35 µM DMC and incubated for 0, 6, 24 and 48 h. The abundance of selective proteins associated with apoptosis was determined by western blotting. Briefly, at the end of the incubation, the cells were harvested and lysed as described previously (18,19). The levels of apoptosisassociated proteins were determined in the cell lysates using primary antibodies (those associated with the cell cycle such as anti-p21, p27, CDC25c, CDK2, cyclin A and cyclin E; those associated with apoptosis such as anti-AIF, Endo G, PARP, Fas-L and Fas; those associated with ER stress such as ATF6α, ATF-6β, IRE1β, GRP78, GADD153, caspase-4 and -12).…”

Section: Reactive Oxygen Species (Ros) Intracellular Camentioning

confidence: 99%

“…The levels of apoptosisassociated proteins were determined in the cell lysates using primary antibodies (those associated with the cell cycle such as anti-p21, p27, CDC25c, CDK2, cyclin A and cyclin E; those associated with apoptosis such as anti-AIF, Endo G, PARP, Fas-L and Fas; those associated with ER stress such as ATF6α, ATF-6β, IRE1β, GRP78, GADD153, caspase-4 and -12). For equal protein loading, each membrane was stripped and reprobed with the anti-β-actin antibody (18,19).…”

Section: Reactive Oxygen Species (Ros) Intracellular Camentioning

confidence: 99%

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Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway

Lien

Liu

et al. 2015

Oncology Reports

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Abstract. Lung cancer is the most common cause of cancerrelated mortality in the US as well as other regions of the world. Curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the major components of Curcuma longa L. It has been reported that curcumin inhibits the growth of various types of cancer cells in vitro and in vivo. However, the mechanisms involved in the inhibition of cell growth and induced apoptosis by DMC in human lung cancer cells remain unclear. In the present study, we investigated the effect of DMC on cell death via the induction of apoptosis in NCI-H460 human lung cancer cells. Flow cytometric assay was used to examine the total percentage of viable cells, the population of cells in the sub-G1 phase of the cell cycle, the level of reactive oxygen species (ROS), Ca 2+ production, mitochondrial membrane potential (ΔΨm) and caspase activity. Western blotting was used to examine the changes in the expression of cell cycle-and apoptosis-associated proteins. Confocal microscopy was used to examine the translocation of apoptosis-associated proteins. The results indicated that DMC significantly induced cell morphological changes and decreased the percentage of viable NCI-H460 cells and DMC induced apoptosis based on the cell distribution in the sub-G1 phase. Moreover, DMC promoted ROS and Ca 2+ production and decreased the level of ΔΨm and promoted the activities of caspase-3, -8 and -9. The Western blotting results showed that DMC promoted the expression of AIF, Endo G and PARP. The levels of Fas ligand (Fas L) and Fas were also upregulated. Furthermore, DMC promoted expression of ER stress-associated proteins such as GRP78, GADD153, IRE1β, ATF-6α, ATF-6β and caspase-4. Based on the findings, we suggest that DMC may be used as a novel anticancer agent for the treatment of lung cancer in the future.

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“…During the last decade, major progress has been made to further understand caspase structure and function, providing a unique basis for drug design (Lavrik et al, 2005;Le et al, 2006;Takai et al, 2012;An et al, 2013, Zou et al, 2013Liu et al, 2014). Caspases belong to the family of cysteinyl aspartate-specific proteases (Chai et al, 2001;Belizario et al, 2008), are activated through proteolysis at specific asparagine residues that are located within the prodomain, the p20 and p10 subunits (Shiozaki et al, 2004;Arockiaraj et al, 2013) This results in the generation of mature active caspases that consist of the heterotetramer p20 2 -p10 2 .…”

Section: Introductionmentioning

confidence: 99%

An in silico Appraisal to Identify High Affinity Anti-Apoptotic Synthetic Tetrapeptide Inhibitors Targeting the Mammalian Caspase 3 Enzyme

Kelotra¹,

Jain²,

Kelotra³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Apoptosis is a general phenomenon of all multicellular organisms and caspases form a group of important proteins central to suicide of cells. Pathologies like cancer, Myocardial infarction, Stroke, Sepsis, Alzheimer's, Psoriasis, Parkinson and Huntington diseases are often associated with change in caspase 3 mediated apoptosis and therefore, caspases may serve as potential inhibitory targets for drug development. In the present study, two series of synthetic acetylated tetrapeptides containing aldehyde and fluromethyl keto groups respectively at the C terminus were proposed. All these compounds were evaluated for binding affinity against caspase 3 structure. In series 1 compound Ac-DEHD-CHO demonstrated appreciable and high binding affinity (Rerank Score: -138.899) against caspase 3. While in series 2 it was Ac-WEVD-FMK which showed higher binding affinity (Rerank Score: -139.317). Further these two compounds met ADMET properties and demonstrated to be nontoxic.

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Distinct Pro-Apoptotic Properties of Zhejiang Saffron against Human Lung Cancer Via a Caspase-8-9-3 Cascade

Cited by 23 publications

References 19 publications

Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells

Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells

Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway

An in silico Appraisal to Identify High Affinity Anti-Apoptotic Synthetic Tetrapeptide Inhibitors Targeting the Mammalian Caspase 3 Enzyme

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