Role of COX-2 in Tumorospheres Derived from a Breast Cancer Cell Line

Singh, Balraj; Cook, Kendra R.; Vincent, Laura; Hall, Carolyn; Martín, C. Campos; Lucci, Anthony

doi:10.1016/j.jss.2010.03.003

Cited by 51 publications

(45 citation statements)

References 37 publications

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“…According to the ICC assay, COX-2 expression was reduced significantly in MCF-7 cells, with no reduction in their CSC-LCs. It has also been observed that celecoxib, at 10 µM, dramatically suppressed the tumorsphere and colony-forming capacity of MCF-7 cells, which is a hallmark of CSCs in vitro (Singh et al, 2011). It was recently demonstrated that celecoxib can effectively harness MDR-1 expression in the doxorubicinresistant MCF-7 cell line, which is mediated by inhibiting AP-1 and NF-κB transcription factors, suggesting the use of a selective COX-2 inhibitor in combination therapy as a promising avenue for successful breast cancer treatment (Chen et al, 2011).…”

Section: Discussionmentioning

confidence: 94%

Effects of celecoxib and L-NAME on apoptosis and cell cycle ofMCF-7 CD44+/CD24–/low subpopulation

Majdzadeh¹,

Aliebrahimi²,

Vatankhah³

et al. 2017

Turk J Biol

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IntroductionBreast cancer is the primary cause of death in malignancies among females (Regulski et al., 2016). It is suggested that a major population of breast tumor was incapable of further growth but only a minute fraction was able to seed new cancers, called cancer stem cells (CSCs) (Al-Hajj et al., 2003). During recent years, studies have identified CSCs as the subpopulation of tumor cells with a unique capacity for self-renewal and the ability to give rise to a heterogeneous population of cancer cells to form tumors. Genomic instability via several gene mutations has been reported to form CSCs from normal stem cells, progenitor cells, or differentiated cells. Cancer development could be due to the fact that CSCs are associated with tumor initiation, progression, and metastasis as well as treatment resistance. Thus, CSCs have been discovered to be a suitable therapeutic target for prevention and treatment of cancer (Soltanian and Matin, 2011;Sotiropoulou et al., 2014). Breast CSCs are multiple, distinct, and nonoverlapping populations coexisting within the tumor mass (Wright et al., 2008). In 2003, breast CSCs with CD44 + /CD24 -/low / ESA + cell surface markers were isolated for the first time by Al-Hajj et al. (2003). Additionally, ALDH1, which belongs to the aldehyde dehydrogenase family, is a putative CSC marker, including breast cancer. To date, several breast cancer stem cell markers have been proposed (CD133, CD29, and CD49f), of which CD44 + /CD24 -/low and ALDH1 are used exclusively to identify these highly tumorigenic cells (Carrasco et al., 2014).The cyclooxygenase enzyme, which mediates prostaglandin production, consists of three isoforms, COX-1, COX-2, and COX-3. COX-1, a house-keeping enzyme, has a crucial role for internal homeostasis. Conversely, COX-2 is undetectable in normal tissues while it is inducible in the setting of neoplasia and inflammation (Regulski et al., 2016). COX-2 upregulation by modulating various signaling pathways can enhance production of prostaglandins, which promote tumor growth, invasion, angiogenesis, and apoptosis resistance. Recent studies have also attributed the overexpression of COX-2 to breast cancer stem-like cell (CSC-LCs) properties and cancer development (Jeong et al., 2010;Singh et al., 2011).

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Section: Discussionmentioning

confidence: 94%

Effects of celecoxib and L-NAME on apoptosis and cell cycle ofMCF-7 CD44+/CD24–/low subpopulation

Majdzadeh¹,

Aliebrahimi²,

Vatankhah³

et al. 2017

Turk J Biol

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“…COX-2 expression has been implicated in CSC proliferation and CSC-assisted metastasis [45,56,57]. As 3 possesses two tolfenamic acid molecules, which are well-known COX-2 inhibitors, flow cytometric studies were conducted to determine if the mechanism of action of 3 involved COX-2 inhibition.…”

Section: Methodsmentioning

confidence: 99%

A Cancer Stem Cell Potent Cobalt(III)–Cyclam Complex Bearing Two Tolfenamic Acid Moieties

2017

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Cancer stem cells (CSCs) are thought to be responsible for cancer relapse. CSCs are a subtype of cancer cells with the ability to differentiate, self-renew, and form secondary or tertiary tumors. Current cancer treatments-including chemotherapy, radiation, and surgery-effectively remove bulk cancer cells but are unable to eliminate CSCs. Here, we present the synthesis, characterization, and anti-CSC properties of a cobalt(III)-cyclam complex bearing two tolfenamic acid moieties, 3. Notably, 3 displays sub-micromolar potency towards breast CSCs and bulk breast cancer cells. Detailed mechanistic studies show that 3 is taken up readily by breast CSCs, enters the nucleus, causes DNA damage, and induces caspase-dependent apoptosis. Furthermore, 3 inhibits cyclooxygenase-2 (COX-2) expression in CSCs. The mechanism of action of 3 is similar to that of a naproxen-appended cobalt(III)-cyclam complex, 1 recently reported by our group. The advantage of 3 over 1 is that it has the potential to remove whole tumor populations (bulk cancer cells and CSCs) with a single dose.

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“…[137][138][139][140][141] In murine models of breast cancer, COX-2 has been shown to be involved in osteoclastogenesis (via IL-11) [138] and stimulation of osteoclasts to resorb bone (via PGE2 and IL-8). [139] It has also been associated with increased tumourgenicity and clonogenicity, conferring genomic instability and changes in cell cycle regulation, including resistance to anoikis, as well as resistance to chemotherapeutic agents ( including doxorubicin).…”

Section: How Nsaids May Influence Cancer Recurrencementioning

confidence: 99%

Does regional anaesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence

Ash

Buggy

2013

Best Practice & Research Clinical Anaesthesiology

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Cancer continues to be a key cause of morbidity and mortality worldwide and its overall incidence continues to increase. Anaesthetists are increasingly faced with the challenge of managing cancer patients, either for surgical resection to debulk or excise the primary tumour, surgical emergencies in patients on chemotherapy, or for the analgesic management of disease-or treatmentrelated chronic pain. Metastatic recurrence is a concern. Surgery and a number of perioperative factors are suspected to accelerate tumour growth and potentially increase the risk of metastatic recurrence. Retrospective analyses have suggested an association between anaesthetic technique and cancer outcomes, and anaesthetists have sought to ameliorate the consequences of surgical trauma and minimize the impact of anaesthetic interventions. Just how anaesthesia and analgesia impact cancer recurrence and consequent survival is very topical, as understanding the potential mechanisms and interactions impacts on the anaesthetist's ability to contribute to the successful outcome of oncological interventions . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 ABSTRACT Cancer continues to be a key cause of morbidity and mortality worldwide and its overall incidence continues to increase. Anaesthetists are increasingly faced with the challenge of managing cancer patients, either for surgical resection to debulk or excise the primary tumour, surgical emergencies in patients on chemotherapy, or for the analgesic management of disease-or treatment-related chronic pain. Metastatic recurrence is a concern. Surgery and a number of perioperative factors are suspected to accelerate tumour growth and potentially increase the risk of metastatic recurrence. Retrospective analyses have suggested an association between anaesthetic technique and cancer outcomes, and anaesthetists have sought to ameliorate the consequences of surgical trauma and minimize the impact of anaesthetic interventions. Just how anaesthesia and analgesia impact cancer recurrence and consequent survival is very topical, as understanding the potential mechanisms and interactions impacts on the anaesthetist"s ability to contribute to the successful outcome of oncological interventions.

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Role of COX-2 in Tumorospheres Derived from a Breast Cancer Cell Line

Abstract: Background-Cyclooxygenase-2 (COX-2) expression in primary breast cancer predicts tumor cell dissemination to bone marrow, which is a risk factor for recurrence and distant metastasis. "Stem-like" phenotype may be important in cancer metastasis.

Cited by 51 publications

References 37 publications

Effects of celecoxib and L-NAME on apoptosis and cell cycle ofMCF-7 CD44+/CD24–/low subpopulation

Effects of celecoxib and L-NAME on apoptosis and cell cycle ofMCF-7 CD44+/CD24–/low subpopulation

A Cancer Stem Cell Potent Cobalt(III)–Cyclam Complex Bearing Two Tolfenamic Acid Moieties

Does regional anaesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence

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