Decisive role of cyclooxygenase-2 and lipocalin-type prostaglandin D synthase in chemotherapeutics-induced apoptosis of human cervical carcinoma cells

Eichele, Karin; Ramer, Robert; Hinz, Burkhard

doi:10.1038/sj.onc.1210962

Cited by 29 publications

(42 citation statements)

References 27 publications

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“…In fact, recent studies indicate a COX-2-dependent pathway underlying apoptosis elicited by the cannabinoid compounds anandamide and its analog R(þ)-methanandamide (18,19). In addition, COX-2 upregulation has been reported to be involved in the proapoptotic action of stearoylethanolamide (20), the alkylphospholipids edelfosin and perifosin (21,22), as well as the chemotherapeutics cisplatin, 5-fluorouracil, and paclitaxel (23,24). About the mechanism underlying COX-2-dependent apoptosis, several studies provided evidence for an activation of the transcription factor PPAR-g by COX-2-dependent PGs of the D-and Jseries (19,(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

“…Proteins were isolated and analyzed as described (18,19,24). Antibodies were from BD Biosciences (COX-2), Santa Cruz (PPAR-g), and Calbiochem (b-actin).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Mol Cancer Ther; 12(1) January 2013 Molecular Cancer Therapeutics 70 PPAR-g mRNA levels were determined by real-time reverse transcriptase PCR (RT-PCR) using the TaqMan RNA-to-C T 1-Step Kit and TaqMan Gene Expression Assays (Applied Biosystems) as described (18,19,24).…”

Section: Quantitative Real-time Rt-pcrmentioning

confidence: 99%

“…In addition, COX-2 upregulation has been reported to be involved in the proapoptotic action of stearoylethanolamide (20), the alkylphospholipids edelfosin and perifosin (21,22), as well as the chemotherapeutics cisplatin, 5-fluorouracil, and paclitaxel (23,24). About the mechanism underlying COX-2-dependent apoptosis, several studies provided evidence for an activation of the transcription factor PPAR-g by COX-2-dependent PGs of the D-and Jseries (19,(24)(25)(26). This view is further corroborated by investigations indicating a pivotal role of PPAR-g activation in eliciting apoptosis of different tumor cells including non-small cell lung cancer cells (NSCLC; refs.…”

Section: Introductionmentioning

confidence: 99%

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COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells

Ramer

Heinemann

Merkord

et al. 2013

Molecular Cancer Therapeutics

178

150

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The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-g in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-g antagonist), and siRNA targeting COX-2 and PPAR-g. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-g mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-g mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD 2 and 15-deoxy-D 12,14 -PGJ 2 (15d-PGJ 2 ) caused a translocation of PPAR-g to the nucleus and induced a PPAR-g-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-g in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-g and a subsequent nuclear translocation of PPAR-g by COX-2-dependent PGs. Mol Cancer Ther; 12(1); 69-82. Ó2012 AACR.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Proteins were isolated and analyzed as described (18,19,24). Antibodies were from BD Biosciences (COX-2), Santa Cruz (PPAR-g), and Calbiochem (b-actin).…”

Section: Western Blot Analysismentioning

confidence: 99%

Section: Quantitative Real-time Rt-pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells

Ramer

Heinemann

Merkord

et al. 2013

Molecular Cancer Therapeutics

178

150

View full text Add to dashboard Cite

show abstract

“…On the other hand, NS-398 at low dose protected HeLa cells against the cytotoxic action of cisplatin, paclitaxel and 5-FU [26]. It is worth mentioning, that Shestopal et al demonstrated that HeLa cells showed the lowest DPD mRNA level among five investigated cell lines [27].…”

Section: Discussionmentioning

confidence: 94%