Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells

Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca2+-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma.

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The ATP-Competitive mTOR Inhibitor INK128 Enhances In Vitro and In Vivo Radiosensitivity of Pancreatic Carcinoma Cells

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-13-2136 ◽

2013 ◽

Vol 20 (1) ◽

pp. 110-119 ◽

Cited By ~ 29

Author(s):

Thomas J. Hayman ◽

Amy Wahba ◽

Barbara H. Rath ◽

Heekyong Bae ◽

Tamalee Kramp ◽

...

Keyword(s):

Pancreatic Carcinoma ◽

Mtor Inhibitor ◽

Carcinoma Cells

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Elevated pressure enhanced TRAIL-induced apoptosis in hepatocellular carcinoma cells via ERK1/2-inactivation

Cellular & Molecular Biology Letters ◽

10.1515/cmble-2015-0030 ◽

2015 ◽

Vol 20 (4) ◽

Cited By ~ 5

Author(s):

Eunyoung Hong ◽

Eunil Lee ◽

Joonhee Kim ◽

Daeho Kwon ◽

Yongchul Lim

Keyword(s):

Specific Inhibitor ◽

Underlying Mechanism ◽

Elevated Pressure ◽

Mitochondrial Pathway ◽

Carcinoma Cells ◽

Intrinsic Resistance ◽

Hep3b Cells ◽

Induced Apoptosis

AbstractThe high frequency of intrinsic resistance to TNF-related apoptosisinducing ligand (TRAIL) in tumor cell lines has necessitated the development of strategies to sensitize tumors to TRAIL-induced apoptosis. We previously showed that elevated pressure applied as a mechanical stressor enhanced TRAIL-mediated apoptosis in human lung carcinoma cells in vitro and in vivo. This study focused on the effect of elevated pressure on the sensitization of TRAIL-resistant cells and the underlying mechanism. We observed elevated pressure-induced sensitization to TRAIL-mediated apoptosis in Hep3B cells, accompanied by the activation of several caspases and the mitochondrial signaling pathway. Interestingly, the enhanced apoptosis induced by elevated pressure was correlated with suppression of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) phosphorylation and CREB without any change to other MAPKs. Phosphorylation of Bcl-2-associated death promoter (BAD) also decreased, leading to inhibition of the mitochondrial pathway. To confirm whether the activation of pERK1/2 plays a key role in the TRAIL-sensitizing effect of elevated pressure, Hep3B cells were pre-treated with the ERK1/2-specific inhibitor PD98059 instead of elevated pressure. Co-treatment with PD98059 and TRAIL augmented TRAIL-induced apoptosis and decreased BAD phosphorylation. The inhibition of ERK1/2 activation by elevated pressure and PD98059 also reduced BH3 interacting-domain death agonist (BID), thereby amplifying apoptotic stress at the mitochondrial level. Our results suggest that elevated pressure enhances TRAIL-induced apoptosis of Hep3B cells via specific suppression of ERK1/2 activation among MAPKs.

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Vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro

British Journal of Cancer ◽

10.1038/bjc.1997.501 ◽

1997 ◽

Vol 76 (8) ◽

pp. 1017-1020 ◽

Cited By ~ 58

Author(s):

KW Colston ◽

SY James ◽

EA Ofori-Kuragu ◽

L Binderup ◽

AG Grant

Keyword(s):

Vitamin D ◽

Pancreatic Carcinoma ◽

Carcinoma Cells ◽

Vitamin D Receptors

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In vitro susceptibility to dexamethasone- and doxorubicin-induced apoptotic cell death in context of maturation stage, responsiveness to interleukin 7, and early cytoreduction in vivo in childhood T-cell acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v99.11.4109 ◽

2002 ◽

Vol 99 (11) ◽

pp. 4109-4115 ◽

Cited By ~ 26

Author(s):

Christian Wuchter ◽

Velia Ruppert ◽

Martin Schrappe ◽

Bernd Dörken ◽

Wolf-Dieter Ludwig ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Apoptotic Cell ◽

Lymphoblastic Leukemia ◽

Therapy Response ◽

Drug Induced ◽

In Vitro Susceptibility ◽

Interleukin 7 ◽

Induced Apoptosis

Within childhood T-cell acute lymphoblastic leukemia (T-ALL), patients with a cortical (CD1a+) immunophenotype have been identified as a subgroup with favorable outcome in the acute lymphoblastic leukemia–Berlin-Frankfurt-Münster (ALL-BFM), Cooperative study group for childhood acute lymphoblastic leukemia (COALL) and Pediatric Oncology Group studies. We investigated in leukemic samples of children with T-ALL (n = 81) whether the different in vivo therapy response could be linked to differential in vitro susceptibility to apoptotic cell death. The extent of dexamethasone- as well as doxorubicin-induced apoptosis, detected by annexin V staining, positively correlated with the expression levels of CD1a (Spearman correlation coefficient, rs = 0.3 and 0.4, respectively; P < .01). When compared to cortical T-ALL, mature (CD1a− , surface CD3+) T-ALL were significantly more resistant to doxorubicin, and immature, pro–/pre–T-ALL were more resistant to both drugs (P < .05). Apoptosis-related parameters (Bax, Bcl-2, CD95, and CD95-induced apoptosis) did not account for differential susceptibility to drug-induced apoptosis. By contrast, an interleukin 7–induced rescue of leukemic cells from spontaneous apoptosis, recently proposed to reflect distinct developmental stages and apoptotic programs in T-ALL, was highly associated with susceptibility to dexamethasone- but not doxorubicin-induced apoptosis (P < .001 versus P = .08). Analysis of clinical data showed that in vitro susceptibility to dexamethasone (but not to doxorubicin) closely correlated with early in vivo therapy response characterized by percentages of blast cells in bone marrow on day 15 (rs = −0.46, P = .001). Taken together, the in vitro assessment of drug-induced apoptosis revealed maturation-dependent differences within childhood T-ALL. The enhanced sensitivity to both drugs in cortical T-ALL might account for the better in vivo treatment response of this prognostically favorable T-ALL subgroup.

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