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

Abstract

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).

One Pot Doxorubicin Partitioning and Encapsulation on Silica Nanoparticle, Applying Aqueous Two Phase System for Preparation of pH-Responsive Nanocarriers

“…MTT assay was employed to study the cytotoxic effect of free drug, blank nanocarriers, and drugloaded nanocarrier 111,112 . 10 4 cells of MCF-7 were cultured on each well of 96-well plates and were incubated for 24h.…”

The effects of L-NAME on DU145 human prostate cancer cell line: A cytotoxicity-based study

“…IC50 was determined as being 12.2 mM in DU145 cells. Majdzadeh et al 27 studied the effect of L-NAME on MCF-7 breast cancer cells and their IC50 was between 10 mM and 20 mM in the MTT test. In their study, the viabilities of MCF-7 cells at 10, 20, and 40 mM of L-NAME were nearly 80%, 40%, and <20%, while in the current study, the viabilities of DU145 cells at 8, 16, and 32 mM of L-NAME were 68.4%, 33.3%, and 12%, respectively.…”

“…In our study, we detected a dose-dependent rise in apoptotic markers and also confirmed this result by morphological analysis. In literature, in the study of Majdzadeh et al, 27 L-NAME was suggested to partially lead to apoptosis and proposed to show its effect by another cell death mechanism. In our study, we found increase in CASP3, CYCY, and Bax immunostaining as well as apoptotic hallmarks morphologically.…”

Recent advances in the development of celecoxib analogs as anticancer agents: A review

“…Several studies [ 33–36 ] evaluated the impact of celecoxib on various cancer cell lines to determine their sensitivity to celecoxib alone or in combination with other anticancer agents. For instance, El‐Awady et al [ 34 ] stated the concentration‐dependent effect of celecoxib on five cancer cell lines (HeLa, HCT116, HepG2, MCF‐7, and U251).…”