Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells

Siddiqui, Rafat A.; Zérouga, Mustapha; Wu, Min; Castillo, Alicia; Harvey, Kevin; Zaloga, Gary P.; Stillwell, William

doi:10.1186/bcr1036

Cited by 117 publications

(72 citation statements)

References 45 publications

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“…However, these data seemed to contradict those obtained by means of the caspase-3 assay, which displayed activation after 24 h. This implies that a more significant number of condensed nuclei would have been visible at 24 and 48 h. It is probable that the cells, having reacted to DHA by activating caspase-3, had completely disappeared by 48 h, and this might explain the low incidence of condensed nuclei; several hours were generally needed to ensure that a cell went through the phenomenon of complete apoptosis once it had undergone the action of caspase-3. Indeed, the increasing numbers of condensed nuclei, which under our conditions reached their highest level of 11% after a longer incubation time, was consistent with the study reported by Siddiqui et al (20), in which the percentage of cells undergoing apoptosis leveled off at 15%. It is also possible that DHA can induce several different pathways leading to apoptosis, and in particular, the Bax pathway that has been described for the HL60 cell line (13).…”

Section: Discussionsupporting

confidence: 81%

Docosahexaenoic acid intake decreases proliferation, increases apoptosis and decreases the invasive potential of the human breast carcinoma cell line MDA-MB-231

Blanckaert

Ulmann²,

Mimouni³

et al. 2010

Int J Oncol

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Abstract. Breast cancer is the most common cancer in women in industrialized countries. Environmental factors, such as differences in diet are likely to have an important influence on cancer emergence. Among these factors, n-3 polyunsaturated-fatty acids, such as docosahexaenoic acid (DHA), are good candidates for preventing breast cancer. Here we investigate the effect of DHA on the human breast cancer cell line MDA-MB-231 and show that DHA incorporation i) has an anti-proliferative effect, ii) induces apoptosis via a transient increase in caspase-3 activity and the promotion of nuclear condensation, and iii) reduces the invasive potential of MDA-MB-231 cells. To conclude, DHA may have beneficial effects as a result of slowing the proliferation of tumor cells, and minimizing their metastatic potential. IntroductionFor several decades, genetic and environmental factors have been explored in order to elucidate the appearance of tumors. Genetic factors are obviously involved in carcinogenesis, but diet is an environmental factor that is likely to have an influence on health (1), and particularly on tumor emergence (2-4). It has been shown that n-3 polyunsaturated, long-chain fatty acids (PUFAs), such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), are able to play an important preventive role in cardiovascular disease (5) and cancer (6). This conclusion is based partly on the observation that the incidence of these diseases is lower in Japanese people, whose diet is seafood based, resulting in a more balanced ratio between n-3 and n-6 PUFA than that of the Western diet (7). Even though this resource may be depleted in the future by the overharvesting of n-3 PUFA rich fish, it could be replaced by using marine microalgae, which have been identified as an important alternative source of DHA and EPA (8,9). Breast cancer is one of the cancers most frequently observed in industrialized countries, and the one with the highest incidence in women. Epidemiological studies have shown that the rate of breast cancer is 4 to 5 times higher in Western countries than in Japan (1,10). The mechanism by which DHA and EPA could provide protection against the appearance of a tumor, or directly influence cancer cells by reducing their malignancy, remains unclear, since cohort studies do not reveal any correlation between fat intake and breast cancer (1). Nevertheless, some evidence hints that DHA not only acts as an anti-proliferative agent by lengthening the cell cycle between the G2/M transition (11), but is also a proapoptotic factor, increasing caspase-3 and Bax (12,13). In addition, DHA has been shown to affect cell proliferation, whatever its source (i.e., fish oil or microalgae) (14). It has also been shown that the n-3 PUFAs and DHA, in particular, can act on lipid peroxidation as well as on the proteins implicated in the ROS mechanism leading to cell death (15,16).In this study, the effects of two concentrations of DHA (20 and 100 μM) were investigated on the human breast cancer cell line MDA-MB-231. DHA incorpo...

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Section: Discussionsupporting

confidence: 81%

Docosahexaenoic acid intake decreases proliferation, increases apoptosis and decreases the invasive potential of the human breast carcinoma cell line MDA-MB-231

Blanckaert

Ulmann²,

Mimouni³

et al. 2010

Int J Oncol

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“…12,34,39 These approaches were designed either to increase efficacy or enhance the specificity of targeted cells. Wang et al combined the use of DHA with the anticancer drug etoposide (VP16) to induce apoptosis in medulloblastoma cell lines, Daoy and D283, and glioblastoma cell lines, U87 and U138.…”

mentioning

confidence: 99%

Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines

Harvey

Saaddatzadeh

et al. 2015

JNS

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abbreviatioNs BCA = bicinchoninic acid; CSC = Cell Systems Corporation; DHA = docosahexaenoic acid; DMEM = Dulbecco's modified essential medium; DPA = docosapentaenoic acid; ED 50 = median effective dose; EMEM = Eagle's minimum essential medium; EPA = eicosapentaenoic acid; FBS = fetal bovine serum; HBMEC = human brain microvascular endothelial cell; HCCMEC = human cerebral cortex microvascular endothelial cell; OD = optical density; PARP = poly (ADP-ribose) polymerase; PBS = phosphate-buffered saline; PUFA = polyunsaturated fatty acid. obJect Glioblastoma is a rapidly infiltrating tumor that consistently rematerializes despite various forms of aggressive treatment. Brain tumors are commonly treated with alkylating drugs, such as lomustine, which are chemotherapeutic agents. Use of these drugs, however, is associated with serious side effects. To reduce the side effects, one approach is to combine lower doses of chemotherapeutic drugs with other nontoxic anticancer agents. In this study, using glioblastoma cell lines, the authors investigated the anticancer effects of lomustine, alone and in combination with docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid normally abundant in the brain and known for its anticancer potential. methods Cells were cultured from 3 human-derived tumor cell lines (U87-MG, DB029, and MHBT161) and supplemented with either DHA or lomustine to determine the growth inhibitory potential using WST-1, a mitochondrial functional indicator. Human-derived cerebral cortex microvascular endothelial cells served as a normal phenotypic control. Cellular incorporation of DHA was analyzed by gas chromatography. Using flow cytometric analysis, the DHA and/or lomustine effect on induction of apoptosis and/or necrosis was quantified; subsequently, the DHA and lomustine effect on cell cycle progression was also assessed. Western blot analysis confirmed the role of downstream cellular targets. results U87-MG growth was inhibited with the supplementation of either DHA (ED 50 68.3 mM) or lomustine (ED 50 68.1 mM); however, growth inhibition was enhanced when U87-MG cells were administered equimolar doses of each compound, resulting in nearly total growth inhibition at 50 mM. Gas chromatography analysis of the fatty acid profile in DHA-supplemented U87-MG cells resulted in a linear dose-dependent increase in DHA incorporation (< 60 mM). The combination of DHA and lomustine potently induced U87-MG apoptosis and necrosis as indicated by flow cytometric analysis. Activation of caspase-3 and poly (ADP-ribose) polymerase (PARP) was evident in lomustine-treated U87-MG cells, although this activation did not appear to be dependent on DHA supplementation. Additionally, lomustine-treated cells' growth arrested in the G 2 /M cell cycle stage, regardless of the presence of DHA. Similar to the U87-MG observations, the combination of DHA and lomustine resulted in growth inhibition of 2 additional human-derived glioblastoma cell lines, DB029 and MHBT161. Importantly, in primary human-derived cerebral corte...

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“…Mammoto et al showed that clinically relevant concentrations of propofol (1-5 μg/ml) decreased the invasion ability of human cancer cells (HeLa, HT1080, HOS and RPMI-7951) in vitro, and furthermore, propofol induced lung metastasis of tumor cells in a mouse model of osteosarcoma (12). Siddiqui RA et al showed that the propofol-DHA or propofol-EPA conjugates significantly inhibit adhesion, migration and induced apoptosis of breast cancer cells, implying that these conjugates may be useful for the treatment of breast cancer (6). However, there are some different results, demonstrating that propofol could enhance the migration of human breast cancer cell lines (13).…”

Section: Discussionmentioning

confidence: 99%

Effects of Sevoflurane or Propofol on Immune Function in Patients Undergoing Hepatectomy

Gao¹,

Song²,

Zhang³

et al. 2017

J Anesth Perioper Med

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Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells

Cited by 117 publications

References 45 publications

Docosahexaenoic acid intake decreases proliferation, increases apoptosis and decreases the invasive potential of the human breast carcinoma cell line MDA-MB-231

Docosahexaenoic acid intake decreases proliferation, increases apoptosis and decreases the invasive potential of the human breast carcinoma cell line MDA-MB-231

Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines

Effects of Sevoflurane or Propofol on Immune Function in Patients Undergoing Hepatectomy

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