Aspirin and metformin exhibit antitumor activity in murine breast cancer

Zhao, Maoyuan; Wang, Yuyi; Du, Chi; Liu, Yanyang; Zhang, Nan; Luo, Feng

doi:10.3892/or.2018.6190

Cited by 9 publications

(7 citation statements)

References 61 publications

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“…Investigation of the literature for a possible explanation revealed tha metformin has a positive role on the secretion of TGF-β in supernatants of 4T1 triple-negative breast cancer cells. 130 …”

Section: Resultsmentioning

confidence: 99%

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Ezzeldeen¹,

Swidan²,

ElMeshad³

et al. 2021

IJN

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Background: Honokiol (HK) is a natural bioactive compound with proven antineoplastic properties against melanoma. However, it shows very low bioavailability when administered orally. Alternatively, topical administration may offer a promising route. The objective of the current study was to fabricate HK transfersomes (HKTs) for topical treatment of melanoma. As an ultradeformable carrier system, transfersomes can overcome the physiological barriers to topical treatment of melanoma: the stratum corneum and the anomalous tumor microenvironment. Moreover, the immunomodulatory and stemness-regulation roles of HKTs were the main interest of this study. Methods: TFs were prepared using the modified scalable heating method. A three-factor, three-level Box-Behnken design was utilized for the optimization of the process and formulation variables. Intracellular uptake and cytotoxicity of HKTs were evaluated in nonactivated and stromal cell-activated B16F10 melanoma cells to investigate the influence of the complex tumor microenvironment on the efficacy of HK. Finally, ELISA and Western blot were performed to evaluate the expression levels of TGF-β and clusters of differentiation (CD47 and CD133, respectively). Results: The optimized formula exhibited a mean size of 190 nm, highly negative surface charge, high entrapment efficiency, and sustained release profile. HKTs showed potential to alleviate the immunosuppressive characteristics of B16F10 melanoma in vitro via downregulation of TGF-β signaling. In addition, HKTs reduced expression of the "do not eat me" signal -CD47. Moreover, HKTs possessed additional interesting potential to reduce the expression of the stem-like cell marker CD133. These outcomes were boosted upon combination with metformin, an antihyperglycemic drug recently reported to possess different functions in cancer, while combination with collagenase, an extracellular matrix-depleting enzyme, produced detrimental effects. Conclusion: HKTs represent a promising scalable formulation for treatment of the aggressive B16F10 melanoma, which is jam-packed with immunosuppressive and stem-like cell markers.

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Section: Resultsmentioning

confidence: 99%

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Ezzeldeen¹,

Swidan²,

ElMeshad³

et al. 2021

IJN

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“…The culture environment has been previously described elsewhere. 16 We purchased cisplatin from Hansoh Pharmaceutical Group Co Ltd (Lianyungang, Jiangsu, China). The recombinant plasmids of CD133 and CD44 were constructed with open reading frames of CD133 and CD44 digested with HindIII and BamHI and subcloned into pcDNA3.1 (+) plasmids for overexpression, and the CD133 and CD44 short hairpin (shRNA) were contained in liposomes for the knockdown.…”

Section: Methodsmentioning

confidence: 99%

“…H460R cells were treated and measured as previously described, 16 double‐stained using fluorescein isothiocyanate (APC)‐conjugated Annexin‐V and propidium iodide (PI) (BD Biosciences, San Jose, CA, USA). PE‐CD133, PE‐CD44, FITC‐CD24 were obtained from eBioscience (Vienna, Austria).…”

Section: Methodsmentioning

confidence: 99%

“…We obtained the human lung cancer cell line H460 cisplatin‐sensitive (H460S) and H460 cisplatin‐resistant (H460R) cells from the National experimental cell resource collection of Chinese Academy of Medical Sciences/Peking Union Medical College (CRC‐PUMC, Beijing, China). The culture environment has been previously described elsewhere 16 . We purchased cisplatin from Hansoh Pharmaceutical Group Co Ltd (Lianyungang, Jiangsu, China).…”

Section: Methodsmentioning

confidence: 99%

“…The tumor volume (major axis) × (minor axis) was monitored every 2–3 days. The mice were sacrificed 21 days after treatment 16 …”

Section: Methodsmentioning

confidence: 99%

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Aspirin overcomes cisplatin resistance in lung cancer by inhibiting cancer cell stemness

2020

Self Cite

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Background Lung cancer is the leading cause of cancer death and is commonly treated by cisplatin. Although cisplatin treatment may initially be successful, its effectiveness usually reduces significantly in disease‐recurrent patients. Aspirin, a nonselective COX inhibitor, has been shown to help reverse the status of cisplatin sensitivity in recurrent human ovarian cancer cells. This study aimed to explore the effect of aspirin on cisplatin resistance through the perspective of cancer cell stemness. Methods We used clustering analysis to predict the H460 cisplatin resistance from the GSE21656 dataset. The increased lung cancer cell stemness may contribute to enhanced tolerance. In this study, we used aspirin, a nonselective COX inhibitor, with cisplatin for several hours in cells and days in vivo, and studied the inhibition against human cisplatin‐resistant H460 cells. H460 cisplatin‐sensitive and H460 cisplatin‐resistant cells were treated with 16 μM aspirin or/and 0.3 μg/mL cisplatin for 72 hours. Results H460 cisplatin‐resistant cells showed stronger resistance, stemness, and invasiveness than H460 cisplatin‐sensitive, and cisplatin significantly reduced the survival of cisplatin‐sensitive cells, while cisplatin with aspirin dramatically reduced the surviving fractions of cisplatin‐resistant cells. Conclusions This study revealed that stemness is a latent inhibitor of the resistance of lung cancer cisplatin‐resistant cells and might be effectively inhibited by aspirin.

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Protective potential of piroxicam on human peripheral blood mononuclear cells against the suppressive capacity of glioblastoma cell lines

Abdesheikhi

Sedghy

Farsinejad

et al. 2022

Sci Rep

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Dexamethasone, a common medication used in the treatment regimen of glioblastoma, has broad inhibitory effects on the immune responses. Here, in an in vitro study, we examined the effects of piroxicam, a potent substitute for dexamethasone, on peripheral blood mononuclear cells (PBMCs) co-cultured with two glioblastoma cell lines, U-87 MG and A-172 cells. MTT assay was used to determine the proliferation of PBMCs treated with piroxicam, or dexamethasone. In addition, to evaluate the effects of drugs on the cell cycle distribution, DNA content per cell was analyzed in PBMCs and A-172 cell lines using flow cytometry. Oxidative parameters, including superoxide dismutase-3 (SOD3) activity and total anti-antioxidant capacity, lactate dehydrogenase (LDH) activity, as well as IFN-γ and TGF-β levels were measured in PBMCs alone or in the presence of cell lines using ELISA. Unlike dexamethasone, piroxicam showed a protective effect on PBMCs against both glioblastoma cell lines. Furthermore, while dexamethasone reduced the proliferation of PBMCs, piroxicam had no adverse effect on the proliferation. Cell cycle analysis showed a reduction in the G2/M phase in piroxicam-treated A-172 cells. Additionally, dexamethasone limited the cell cycle progression by increasing the fraction of PBMCs in G0/G1. Interestingly, after co-culturing piroxicam-treated PBMCs with cell lines, a remarkable rise in the LDH activity was observed. Although not significant, piroxicam partially decreased TGF-β levels in both cell lines. Our findings suggested a protective effect of piroxicam, but not dexamethasone, on PBMCs against inhibitory mechanisms of two glioblastoma cell lines, U-87 and A-172 cells.

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Aspirin and metformin exhibit antitumor activity in murine breast cancer

Cited by 9 publications

References 61 publications

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Aspirin overcomes cisplatin resistance in lung cancer by inhibiting cancer cell stemness

Protective potential of piroxicam on human peripheral blood mononuclear cells against the suppressive capacity of glioblastoma cell lines

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