Increased sensitivity of African American triple negative breast cancer cells to nitric oxide-induced mitochondria-mediated apoptosis

Martinez, Luis; Thames, Easter C.; Kim, Jinna; Chaudhuri, Gautam; Singh, Rajan; Pervin, Shehla

doi:10.1186/s12885-016-2547-z

Cited by 13 publications

(12 citation statements)

References 48 publications

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“…A dose-dependent elevation of nitrosative stress in the MDA-MB-231 cells has been observed with the treatment of LMWF in each time-point, and it is positively correlated to the dosage of LMWF. Although the increase in NO was consistent with the dose-dependent inhibitory effect by LMWF on the MDA-MB-231 cells, these cells were functionally unable to carry out the NO-mediated apoptosis [54]. The NO resistance in the MDA-MB-231 cells and the protective role of the low-concentration of NO, in cells [55], may explain why the cell viability of the MDA-MB-231 cells that was inhibited by a LMWF in lower concentrations (<150 µg/mL), was slowly reversed in the methylthiazol-diphenyl-tetrazolium (MTT) assays of this study.…”

Section: Resultsmentioning

confidence: 65%

Fucoidan Extracted from the New Zealand Undaria pinnatifida—Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines

Shi

Chen

et al. 2018

Marine Drugs

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Fucoidan, the complex fucose-containing sulphated polysaccharide varies considerably in structure, composition, and bioactivity, depending on the source, species, seasonality, and extraction method. In this study, we examined five fucoidans extracted from the same seaweed species Undaria pinnatifida but from different geological locations, and compared them to the laboratory-grade fucoidan from Sigma (S). The five products differed in molecular composition. The amount of over 2 kDa low molecular weight fraction (LMWF) of the New Zealand crude fucoidan (S1) was larger than that of S, and this fraction was unique, compared to the other four fucoidans. The difference of molecular compositions between S and S1 explained our previous observation that S1 exhibited different anticancer profile in some cancer cell lines, compared with S. Since we observed this unique LMWF, we compared the cytotoxic effects of a LMWF and a high molecular weight fucoidan (HMWF) in two breast cancer cell lines—MCF-7 and MDA-MB-231. Results indicated that the molecular weight is a critical factor in determining the anti-cancer potential of fucoidan, from the New Zealand U. pinnatifida, as the LMWF exhibited a dose-dependent inhibition on the proliferation of breast cancer cells, significantly better than the HMWF, in both cell lines. A time-dependent inhibition was only observed in the MCF-7. Induction of caspase-dependent apoptosis was observed in the MDA-MB-231 cells, through the intrinsic apoptosis pathway alone, or with the extrinsic pathway. LMWF stimulated a dose-dependent NOS activation in the MDA-MB-231 cells. In conclusion, the fucoidan extracted from the New Zealand U. pinnatifida contains a unique LMWF, which could effectively inhibit the growth of breast cancer cell lines. Therefore, the LMWF from New Zealand U. pinnatifida could be used as a supplement cancer treatment.

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Section: Resultsmentioning

confidence: 65%

Fucoidan Extracted from the New Zealand Undaria pinnatifida—Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines

Shi

Chen

et al. 2018

Marine Drugs

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“…Nitric oxide (NO) has both pro- and anti-apoptotic effects on cancer cells, mainly depending on its concentration [27-30]. Physiological level of NO signaling is essential for cell survival and proliferation, and depletion of NO inhibits proliferation and induces apoptosis in various cancer cells [31, 32].…”

Section: Introductionmentioning

confidence: 99%

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Zhu

Wang

Zhou

et al. 2017

Cell Physiol Biochem

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Background/Aims: The effects of zinc signaling on proliferation or apoptosis of leukemia cells remain elusive. In the present study, we used N, N, N’, N’-tetrakis-(2-pyridylmethyl)-ethylene-diamine (TPEN), a membrane-permeable zinc chelator, to evaluate the effect of zinc depletion on survival and apoptosis of NB4 acute promyelocytic leukemia (APL) cells. Methods: The pro-apoptotic effects of TPEN on NB4 cells were examined by flow cytometry, and observed using an optical microscope. Intracellular labile zinc, nitric oxide (NO) or reactive oxygen species (ROS) changes caused by TPEN were measured by flow cytometry. We then explored possible roles of the crosstalk between intracellular labile zinc signaling and nitric oxide signaling in TPEN-triggered apoptosis. Results: we found that TPEN induced apoptosis in NB4 APL cells in a dosage-dependent manner. We further demonstrated that TPEN triggered apoptosis by attenuating intracellular zinc and nitric oxide signaling in NB4 cells. Both exogenous zinc supplement and the nitric donor sodium nitroprusside (SNP) pre-incubation reversed TPEN-mediated inhibition of intracellular NO and Zn²⁺ signaling, and rescued NB4 cells from apoptosis. Conclusion: These results suggest for the first time that crosstalk between zinc signaling and nitric oxide pathway is essential for the survival of NB4 cells. TPEN induces apoptosis in NB4 cells via negatively regulating intracellular NO and Zn²⁺ signaling. Our in vitro data suggest that zinc depletion by TPEN may be a potential therapeutic strategy for APL.

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“…The treatment options for TBNC are limited to surgery, radiation, or conventional chemotherapy because few targeted therapies are available [ 15 ]. TNBC is a very heterogeneous disease and can be divided into different molecular subtypes: immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), basal-like 1 and 2 (BL1 and BL2), and luminal androgen receptor (LAR) or African American (AA) type and Caucasian (CA) type [ 6 , 7 ]. Each TNBC subtype has its own unique ontology and responds differently to standard of care (SOC) treatments [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…TNBC is a very heterogeneous disease with at least six molecular subtypes: immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), basal-like 1 and 2 (BL1 and BL2), and luminal androgen receptor (LAR) [ 6 ]. TNBC can also be divided according to race into African American (AA) type and Caucasian (CA) type [ 7 ]. These TNBC subtypes have different responses to standard of care (SOC) treatments, because each of them has its own unique ontology [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Triterpenoid Saponin AG8 from Ardisia gigantifolia stapf. Induces Triple Negative Breast Cancer Cells Apoptosis through Oxidative Stress Pathway

Wang

Tang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Triple-negative breast cancers (TNBCs) are associated with poor patient survival because of the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions. Our previous studies have shown that the triterpenoid saponin AG8 from Ardisia gigantifolia stapf. inhibits the proliferation of MDA-MB-231 cells. In this study, the effects of AG8 were further analyzed in different TNBC cell types: MDA-MB-231, BT-549, and MDA-MB-157 cells. AG8 inhibited the viability of MDA-MB-231, BT-549, and MDA-MB-157 cells in a dose-dependent manner and showed stronger cytotoxicity to African American (AA) and mesenchymal (M) subtypes than Caucasian (CA) and mesenchymal stem-like (MSL) subtypes, respectively. AG8 impaired the uptake of MitoTracker Red CMXRos by the mitochondria of TNBC cells in a dose-dependent manner, and this was recovered by N-acetyl-l-cysteine (NAC). AG8 affected GSH, SOD, and MDA levels of TNBC cells, but different TNBC subtypes had different sensitivities to AG8 and NAC. In addition, we found that AG8 increased the Bax/Bcl-2 ratio and the levels of cytoplasmic cytochrome c and significantly decreased phosphorylation of ERK and AKT in BT549 and MDA-MB-157 cells. AG8 elicited its anticancer effects through ROS generation, ERK and AKT activation, and by triggering mitochondrial apoptotic pathways in TNBC cells. AG8 had selective cytotoxic effects against the AA and M TNBC subtypes and markedly induced MDA-MB-157 (AA subtype) cell apoptosis through pathways that were not associated with ROS, which was different from the other two subtypes. The underlying mechanisms should be further investigated.

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Increased sensitivity of African American triple negative breast cancer cells to nitric oxide-induced mitochondria-mediated apoptosis

Cited by 13 publications

References 48 publications

Fucoidan Extracted from the New Zealand Undaria pinnatifida—Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines

Fucoidan Extracted from the New Zealand Undaria pinnatifida—Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Triterpenoid Saponin AG8 from Ardisia gigantifolia stapf. Induces Triple Negative Breast Cancer Cells Apoptosis through Oxidative Stress Pathway

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