Nonsteroidal anti‐inflammatory drugs suppress cancer stem cells <i>via</i> inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer

Moon, Chang Mo; Kwon, Ji-Won; Kim, Ji Suk; Oh, Sun Hee; Lee, Kyung Jin; Park, Sung Chul; Hong, Sung Pil; Cheon, Jae Hee; Kim, Tae Il

doi:10.1002/ijc.28381

Cited by 87 publications

(81 citation statements)

References 49 publications

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“…Mechanistically, it has been proposed that the anticancer effect of ASA is mediated through COX-dependent 36,37,57,58 and -independent pathways. 53,54,59 Recent studies have shown that MCF-7 mammospheres are insensitive to the cyclooxygenase pathway, and the COX-2 inhibitor (Indomethacin) was unable to reduce the mammosphere-forming capacity of MDA-MB-231 cells.…”

Section: Discussionmentioning

confidence: 99%

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition

Maity

Das

et al. 2015

Laboratory Investigation

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Acetylsalicylic acid (ASA), also known as aspirin, a classic, nonsteroidal, anti-inflammatory drug (NSAID), is widely used to relieve minor aches and pains and to reduce fever. Epidemiological studies and other experimental studies suggest that ASA use reduces the risk of different cancers including breast cancer (BC) and may be used as a chemopreventive agent against BC and other cancers. These studies have raised the tempting possibility that ASA could serve as a preventive medicine for BC. However, lack of in-depth knowledge of the mechanism of action of ASA reshapes the debate of risk and benefit of using ASA in prevention of BC. Our studies, using in vitro and in vivo tumor xenograft models, show a strong beneficial effect of ASA in the prevention of breast carcinogenesis. We find that ASA not only prevents breast tumor cell growth in vitro and tumor growth in nude mice xenograft model through the induction of apoptosis, but also significantly reduces the self-renewal capacity and growth of breast tumor-initiating cells (BTICs)/breast cancer stem cells (BCSCs) and delays the formation of a palpable tumor. Moreover, ASA regulates other pathophysiological events in breast carcinogenesis, such as reprogramming the mesenchymal to epithelial transition (MET) and delaying in vitro migration in BC cells. The tumor growth-inhibitory and reprogramming roles of ASA could be mediated through inhibition of TGF-β/ SMAD4 signaling pathway that is associated with growth, motility, invasion, and metastasis in advanced BCs. Collectively, ASA has a therapeutic or preventive potential by attacking possible target such as TGF-β in breast carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition

Maity

Das

et al. 2015

Laboratory Investigation

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“…Aspirin may affect apoptosis through prostaglandin-dependent or prostaglandin-independent pathways (44). In prostaglandin-dependent pathways, the inhibition of COX, particularly COX-2, is the primary mechan is minvolved in CRC suppression by aspirin (8)(9)(10)(11). COX-2 is undetectable in the normal epithelium, but is detectable in >80% of patients with CRC and is associated with larger tumor size and deeper tissue invasion (45).…”

Section: Discussionmentioning

confidence: 99%

“…Compared with other types of malignant tumors, CRC is relatively sensitive to aspirin treatment, as revealed by several independent clinical trials (5-7). A number of studies have also demonstrated that COX-2 inhibition is an important strategy for the chemopreventive treatment of colon-associated disorders (8)(9)(10)(11), resulting in a lower risk of cancer. The inhibition of COX-2-dependent signaling pathways is one mechanism involved in the good tumor-suppressive efficacy of aspirin.…”

Section: Introductionmentioning

confidence: 99%

TGF‑β1 mediates the effects of aspirin on colonic tumor cell proliferation and apoptosis

Wang

Zhang

et al. 2018

Oncol Lett

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Abstract. Previous studies have demonstrated that aspirin serves an important role in chemoprevention and the suppression of colorectal cancer (CRC); however, the underlying mechanisms for this inhibition by aspirin remain unclear. Aspirin is capable of promoting apoptosis through prostaglandin-dependent orprostaglandin-independent signaling pathways. In the prostaglandin-dependent pathways, inhibition of cyclooxygenase (COX), particularly COX-2, is the primary mechanism known to be involved in aspirin-induced CRC suppression. Previous studies have implicated prostaglandin-independent signaling pathways and certain associated proteins, including SOX7, in aspirin-induced CRC suppression. In the present study, a newly-characterized association between aspirin, transforming growth factor (TGF)-β1 and CRC inhibition was identified. Specifically, aspirin triggers CRC cell apoptosis by inducing the secretion of TGF-β1, and the increased TGF-β1 then leads to apoptosis and proliferation inhibition in CRC cells.

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“…Moon и соавт. [19] провели исследование механиз-мов действия НПВС. Авторы установили супрессивное влияние НПВС на стволовые опухолевые клетки, от-ветственные за рецидивы и генерализацию опухолево-го процесса.…”

Section: Abstract: Nonsteroidal Anti-inflammatory Drugs Cyclooxygenaunclassified

Effect of nonsteroidal ant-inflammatory drugs on carcinogenesis

Сергеева¹,

Свиридова²,

Кувшинова³

2015

Onkol. Z. im. P.A. Gercena

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72Традиционно при доклинических испытаниях новых лекарственных средств проводят их тестирование на кан-церогенность, т.е. оценивают возможность вызывать раз-витие злокачественных опухолей, а также, в ряде случаев, изучают их влияние на опухолевые клетки in vitro или раз-витие перевивных опухолей у лабораторных животных. Такие исследования обосновывают ограничения или предостережения при использовании тех или иных лекар-ственных средств у онкологических больных.С другой стороны, в последнее 10-летие накопились клинические и экспериментальные данные и о позитив-ных, ассоциированных с онкологией, действиях лекар-ственных препаратов. В частности, это касается профи-лактического/противоопухолевого действия статинов и антидиабетических средств [цит. по 1], ингибиторов про-тонной помпы [2-4] и нестероидных противовоспали-тельных средств (НПВС).Представленный анализ литературы относительно действия НПВС на опухолевые клетки и на динамику развития опухолевого процесса (в основном в экспери-ментальных исследованиях) необходим для оценки це-лесообразности использования НПВС при применении материалов, предназначенных для имплантации в кост-ные дефекты после удаления метастазов в костной ткани у онкологических больных. Адресная доставка противовос-палительных лекарственных средств в область костного дефекта и их высвобождение при деградации материала, а также с его поверхности непосредственно в зоне дефек-та может существенно снизить частоту воспалительных осложнений и создать благоприятные условия для репа-ративного остеогенеза, если это не будет стимулировать развитие опухолевого процесса.Исторически первым было высказано предполо-жение о том, что длительное применение НПВС как ингибиторов циклооксигеназы-2 (ЦОГ-2) может быть своеобразной «химиопрофилактикой» колоректального рака [5]. Y. Guo и соавт.[6] предположили, что НПВС уменьшают риск рецидивирования колоректального рака за счет существенного снижения способности опухоле-вых клеток к миграции вследствие блокирования ЕGF-опосредованного транспорта кальция в клетки. В двой-ном слепом рандомизированном исследовании [7] было доказано, что использование НПВС при семейном поли-позе кишечника приводит к значимому замедлению роста The review summarizes data on the in vitro effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the expression of a number of genes, the proliferation and apoptosis of a number of tumor cell cultures, and the growth of transplantable human malignant tumor cell lines. of human malignant neoplasms. It gives data on the effect of NSAIDs in colorectal cancer and recurrent breast cancer. There is evidence for the safety and expediency of using NDAIDs in replacement of bone tissue after surgical removal of bony metastases in cancer patients.

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Nonsteroidal anti‐inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer

Cited by 87 publications

References 49 publications

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition

TGF‑β1 mediates the effects of aspirin on colonic tumor cell proliferation and apoptosis

Effect of nonsteroidal ant-inflammatory drugs on carcinogenesis

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