A Novel MMP-2 Inhibitor 3-azidowithaferin A (3-azidoWA) Abrogates Cancer Cell Invasion and Angiogenesis by Modulating Extracellular Par-4

Rah, Bilal; Amin, Hina; Yousuf, Khalid; Khan, Sheema; Jamwal, Gayatri; Mukherjee, Debaraj; Goswami, Anindya

doi:10.1371/journal.pone.0044039

Cited by 96 publications

(101 citation statements)

References 46 publications

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“…The colorimetric readout was measured by TECAN microplate reader (Infinite M200 PRO) at 570 nm. The percent cell viability was determined according to the protocol described earlier (Rah et al 2012), and the characteristic sigmoid curve was obtained by using GraphPad Prism software.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21waf-1

Chakraborty

Rasool

Kumar

et al. 2016

AGE

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Stress-induced premature senescence (SIPS) is quite similar to replicative senescence that is committed by cells exposed to various stress conditions viz. ultraviolet radiation (DNA damage), hydrogen peroxide (oxidative stress), chemotherapeutic agents (cytotoxic threat), etc. Here, we report that cristacarpin, a natural product obtained from the stem bark of Erythrina suberosa, promotes endoplasmic reticulum (ER) stress, leading to sub-lethal reactive oxygen species (ROS) generation and which eventually terminates by triggering senescence in pancreatic and breast cancer cells through blocking the cell cycle in the G1 phase. The majority of cristacarpin-treated cells responded to conventional SA-β-gal stains; showed characteristic p21 waf1 upregulation along with enlarged and flattened morphology; and increased volume, granularity, and formation of heterochromatin foci-all of these features are the hallmarks of senescence. Inhibition of ROS generation by N-acetyl-L-cysteine (NAC) significantly reduced the expression of p21 waf1 , confirming that the modulation in p21 waf1 by anti-proliferative cristacarpin was ROS dependent. Further, the elevation in p21 waf1 expression in PANC-1 and MCF-7 cells was consistent with the decrease in the expression of Cdk-2 and cyclinD1. Here, we provide evidence that cristacarpin promotes senescence in a p53-independent manner. Moreover, cristacarpin treatment induced p38MAPK, indicating the ROS-dependent activation of the MAP kinase pathway, and thus abrogates the tumor growth in mouse allograft tumor model.

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Section: Cell Viability Assaymentioning

confidence: 99%

Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21waf-1

Chakraborty

Rasool

Kumar

et al. 2016

AGE

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“…As the parent molecule withaferin A is a known cytotoxic agent, and therefore we examined the effect of 3-AWA (a potential derivative of a-b-unsaturated functionality of ring A of withaferin A) treatment in CaP cells. 9 The a-b-unsaturated carbonyl moiety is present in a plethora of natural products exhibiting effective chemopreventive and chemoprotective activities. 9 Thus, inclusion of an a-b-unsaturated carbonyl group renders a high degree of specificity to overcome drug resistance (see ref 8 and additional references within).…”

Section: A Lower Concentration Of 3-awa Induces Autophagy In Prostatementioning

confidence: 99%

“…9 The a-b-unsaturated carbonyl moiety is present in a plethora of natural products exhibiting effective chemopreventive and chemoprotective activities. 9 Thus, inclusion of an a-b-unsaturated carbonyl group renders a high degree of specificity to overcome drug resistance (see ref 8 and additional references within). Recently, we have reported 3-AWA as a promising cytotoxic and anti-invasive molecule that is superior over its parent compound withaferin A, 9 previously described to promote autophagy in breast cancer cells.…”

Section: A Lower Concentration Of 3-awa Induces Autophagy In Prostatementioning

confidence: 99%

“…9 Thus, inclusion of an a-b-unsaturated carbonyl group renders a high degree of specificity to overcome drug resistance (see ref 8 and additional references within). Recently, we have reported 3-AWA as a promising cytotoxic and anti-invasive molecule that is superior over its parent compound withaferin A, 9 previously described to promote autophagy in breast cancer cells. 7 Therefore, experiments were set up to examine whether 3-AWA could also promote and sustain autophagy in aggressive hormone-independent CaP cells.…”

Section: A Lower Concentration Of 3-awa Induces Autophagy In Prostatementioning

confidence: 99%

“…9 As a dietary constituent, withanolides from Withania somnifera are considered promising anticancer candidates and induced PAWR/Par-4 (PRKC, apoptosis, WT1, regulator) in prostate cancer cells. 10 PAWR, on the other hand is an ubiquitously expressed (in all tissues and organs) tumor suppressor, exhibiting diverse physiological functions in normal and cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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PAWR-mediated suppression of BCL2 promotes switching of 3-azido withaferin A (3-AWA)-induced autophagy to apoptosis in prostate cancer cells

Rah¹,

Rasool²,

Nayak³

et al. 2015

Autophagy

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Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth

Yan

et al. 2019

Cancer Medicine

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Transmembrane serine proteases have been implicated in the development and progression of solid and hematological cancers. Human airway trypsin‐like protease 4 (HAT‐L4) is a transmembrane serine protease expressed in epithelial cells and exocrine glands. In the skin, HAT‐L4 is important for normal epidermal barrier function. Here, we report an unexpected finding of ectopic HAT‐L4 expression in neutrophils and monocytes from acute myeloid leukemia (AML) patients. Such expression was not detected in bone marrow cells from normal individuals or patients with chronic myeloid leukemia, acute lymphocytic leukemia and chronic lymphocytic leukemia. In AML patients who underwent chemotherapy, persistent HAT‐L4 expression in bone marrow cells was associated with minimal residual disease and poor prognostic outcomes. In culture, silencing HAT‐L4 expression in AML–derived THP‐1 cells by short hairpin RNAs inhibited matrix metalloproteinase‐2 activation and Matrigel invasion. In mouse xenograft models, inhibition of HAT‐L4 expression reduced the proliferation and growth of THP‐1 cell–derived tumors. Our results indicate that ectopic HAT‐L4 expression is a pathological mechanism in AML and that HAT‐L4 may be used as a cell surface marker for AML blast detection and targeting.

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A Novel MMP-2 Inhibitor 3-azidowithaferin A (3-azidoWA) Abrogates Cancer Cell Invasion and Angiogenesis by Modulating Extracellular Par-4

Cited by 96 publications

References 46 publications

Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21waf-1

Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21waf-1

PAWR-mediated suppression of BCL2 promotes switching of 3-azido withaferin A (3-AWA)-induced autophagy to apoptosis in prostate cancer cells

Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth

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