Reversal of boswellic acid analog BA145 induced caspase dependent apoptosis by PI3K inhibitor LY294002 and MEK inhibitor PD98059

Pathania, Anup Singh; Joshi, Amit; Kumar, Suresh; Guru, Santosh Kumar; Bhushan, Shashi; Sharma, Parduman R.; Bhat, Wajid Waheed; Saxena, Ajit Kumar; Singh, Jaswant; Shah, Bhahwal Ali; Andotra, Samar S.; Taneja, Subhash C.; Malik, Fayaz; Kumar, Ajay

doi:10.1007/s10495-013-0889-4

Cited by 15 publications

(22 citation statements)

References 31 publications

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“…It is also well known that agents induced apoptosis via caspase‐dependent and ‐independent pathways (Pathania et al, ; Chen et al, ), herein, our results from Figure (A–C) indicated that α‐PA promoted the activities of caspase‐8, −9, and −3. On the basis of these observations, we suggested that α‐PA induced apoptosis in WEHI‐3 cells through the caspase‐dependent pathway.…”

Section: Resultssupporting

confidence: 75%

Alpha‐phellandrene‐induced apoptosis in mice leukemia WEHI‐3 cells in vitro

Lin

Hsu

et al. 2015

Environmental Toxicology

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Although reports have shown that α-phellandrene (α-PA) is one of the monoterpenes and is often used in the food and perfume industry, our previous studies have indicated that α-PA promoted immune responses in normal mice in vivo. However, there is no available information to show that α-PA induced cell apoptosis in cancer cells, thus, we investigated the effects of α-PA on the cell morphology, viability, cell cycle distribution, and apoptosis in mice leukemia WEHI-3 cells in vitro. Results indicated that α-PA induced cell morphological changes and decreased viability, induced G0/G1 arrest and sub-G1 phase (apoptosis) in WEHI-3 cells. α-PA increased the productions of reactive oxygen species (ROS) and Ca and decreased the levels of mitochondrial membrane potential (ΔΨ ) in dose- and time-dependent manners in WEHI-3 cells that were analyzed by flow cytometer. Results from confocal laser microscopic system examinations show that α-PA promoted the release of cytochrome c, AIF, and Endo G from mitochondria in WEHI-3 cells. These results are the first findings to provide new information for understanding the mechanisms by which α-PA induces cell cycle arrest and apoptosis in WEHI-3 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1640-1651, 2016.

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Section: Resultssupporting

confidence: 75%

Alpha‐phellandrene‐induced apoptosis in mice leukemia WEHI‐3 cells in vitro

Lin

Hsu

et al. 2015

Environmental Toxicology

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“…At present, Mcl‐1 is an attractive target for novel gene therapy strategies in different types of carcinomas and has been related to anti‐apoptosis and increased resistance to chemotherapy in human malignancies . Some studies have shown that expression of Mcl‐1 is regulated by the JAK/STAT, MAPK and PI‐3K signaling pathways and that these signaling pathways are distinct from other signal transduction pathways for the regulation of cell stress, growth, proliferation, differentiation and apoptosis . Moreover, Mcl‐1 knockdown induces cell apoptosis after inhibition of the pro‐survival JAK/STAT, MAPK and PI‐3K signaling pathways .…”

mentioning

confidence: 99%

“…Some studies have shown that expression of Mcl‐1 is regulated by the JAK/STAT, MAPK and PI‐3K signaling pathways and that these signaling pathways are distinct from other signal transduction pathways for the regulation of cell stress, growth, proliferation, differentiation and apoptosis . Moreover, Mcl‐1 knockdown induces cell apoptosis after inhibition of the pro‐survival JAK/STAT, MAPK and PI‐3K signaling pathways . However, the signaling pathways that influence Mcl‐1 expression after MTB infection have not been studied.…”

mentioning

confidence: 99%

Suppression of Mcl‐1 induces apoptosis in mouse peritoneal macrophages infected with Mycobacterium tuberculosis

Wang

et al. 2016

Microbiology and Immunology

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The effect of myeloid cell leukemia-1 (Mcl-1) inhibition on apoptosis of peritoneal macrophages in mice infected with Mycobacterium tuberculosis was investigated and the primary signaling pathway associated with the transcriptional regulation of Mcl-1 was identified. Real-time PCR and western blotting indicated that Mcl-1 transcript and protein expression are upregulated during infection with virulent M. tuberculosis H37Rv and Xinjiang strains but not with attenuated M. tuberculosis strain H37Ra or Bacillus Calmette-Guérin. Mcl-1 transcript and protein expression were downregulated by specific inhibitors of the Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K) pathways (AG490, PD98059 and LY294002, respectively). The strongest inhibitor of Mcl-1 expression was PD98059, the MAPK inhibitor. Flow cytometry demonstrated that the rate of apoptosis in peritoneal macrophages is significantly higher in mice infected with M. tuberculosis and the rate of apoptosis is correlated with the virulence of the strain of M. tuberculosis. Apoptosis was found to be upregulated by AG490, PD98059 and LY294002, whereas inhibition of the MAPK pathway sensitized the infected macrophages to apoptosis. Taken together, these results suggest that specific downregulation of Mcl-1 significantly increases apoptosis of peritoneal macrophages and that the MAPK signaling pathway is the primary mediator of Mcl-1 expression.

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“…Protein content was measured by Bradford reagent (Bio-Rad) and 30–70 µg protein amount were run by using SDS-PAGE followed by western blotting as described earlier [17].…”

Section: Methodsmentioning

confidence: 99%

The Synthetic Tryptanthrin Analogue Suppresses STAT3 Signaling and Induces Caspase Dependent Apoptosis via ERK Up Regulation in Human Leukemia HL-60 Cells

et al. 2014

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Tryptanthrin is a natural product which has been reported to have several medicinal properties. In this study, we tried to investigate the detailed molecular mechanism of its bromo analogue (TBr), a potent cytotoxic agent in the induction of cancer cell death. It was found that TBr primarily targets STAT3 and ERK signaling during the induction of apoptosis in several human leukemia cell lines. In HL-60 cells, TBr treatment caused early down regulation of p-STAT3 with concomitant up regulation of p-ERK which led to the activation of intrinsic and extrinsic pathways of apoptosis. The mechanism of TBr mediated inhibition of p-STAT3 was found to be due to the activation of ubiquitin dependent degradation of tyrosine 705 and serine 727 p-STAT3. As IL-6 is the main driver of the STAT3 pathway, the effect of TBr on cell death was subdued when treated in the combination with IL-6 in HL60 cells. Interestingly, PD98059 significantly reduced the apoptotic effects of TBr, thus showing the direct involvement of p-ERK in TBr mediated cell death. It was further shown that apoptotic protein Bax silencing in HL-60 cells resists TBr mediated ERK dependent apoptosis. In summary, for the first time we report the mechanism of TBr mediated cell death in human leukemia cell lines by targeting STAT3 and ERK pathways.

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Reversal of boswellic acid analog BA145 induced caspase dependent apoptosis by PI3K inhibitor LY294002 and MEK inhibitor PD98059

Cited by 15 publications

References 31 publications

Alpha‐phellandrene‐induced apoptosis in mice leukemia WEHI‐3 cells in vitro

Alpha‐phellandrene‐induced apoptosis in mice leukemia WEHI‐3 cells in vitro

Suppression of Mcl‐1 induces apoptosis in mouse peritoneal macrophages infected with Mycobacterium tuberculosis

The Synthetic Tryptanthrin Analogue Suppresses STAT3 Signaling and Induces Caspase Dependent Apoptosis via ERK Up Regulation in Human Leukemia HL-60 Cells

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