Histone Deacetylase Inhibitors Enhance Cytotoxicity Towards Breast Tumors While Preserving the Wound-Healing Function of Adipose-Derived Stem Cells

Koko, Kiavash R.; Chang, Shaohua; Hagaman, Ashleigh L.R.; Fromer, Marc W.; Nolan, Ryan S.; Gaughan, John; Zhang, Ping; Carpenter, Jeffrey P.; Brown, Spencer A.; Matthews, Martha S.; Bird, Dorothy

doi:10.1097/sap.0000000000001066

Cited by 9 publications

(6 citation statements)

References 46 publications

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“…Other researchers suggested that stem cells work through two mechanisms of action, firstly they attenuate the general inflammatory response and secondly, they transform into mature native cell types involved in wound healing such as fibroblasts, antigen presenting cells and endothelial progenitor cells [33,40] . The significant increase in VEGF immunoreactivity in subgroup Va (ADSCs treated) in comparison with subgroups IIIa and IVa could be explained by some authers who reported that ADSCs have angiogenic effects on both endothelial cells and keratinocytes which are sources of VEGF contributing to the acceleration of re-epithelization and wound closure [29,41] .…”

Section: Discussionmentioning

confidence: 99%

A Histological and Immuno-histchemical study on the Effect of Atorvastatin versus Adipose Derived Stem Cells on Cutaneous Wound Healing in Diabetic Male Albino Rats

Elmohsen

Salama

Abdelaziz

et al. 2020

Egyptian Journal of Histology

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Background: About 15% of the 150 million people with diabetes worldwide suffer from foot ulcerations, which often become non-healing chronic wounds. Atorvastatin has anti-inflammatory, fibro proliferative, microvascular pleiotropic properties and able to control wound healing process. Adipose-derived stem cells (ADSCs) provide an attractive source of cell therapy for regeneration of damaged skin being able to self-renewal and differentiating into various cells. Aim of the Work: To evaluate and compare the effect of atorvastatin versus ADSCs on cutaneous wound healing in diabetic rats. Materials and Methods: 85 adult male albino rats one for ADSCs preparation and others were divided into six groups each of them was subdivided into subgroups a & b as follow: Subgroup a was sacrificed after 7 days of wounding. Subgroup b was sacrificed after 14 days of wounding. GI control, GII (wounded, non-diabetic rats), GIII (non-treated, wounded diabetic group), GIV (Vaseline and lanoline treated wounded diabetic), GV (ADSCs treated, wounded diabetic rats) injected with single intradermal ADSCs at the edge of the wound one day post wounding. GVI (atorvastatin treated wounded diabetic rats) .Skin specimens were taken from the wound site, processed and stained with H&E, Masson's trichrome and immunohistochemical stain for vascular endothelial growth factor (VEGF). Results: Wounds of diabetic groups (III &IV) showed delayed healing of wound as compared to the non diabetic group II with failure of re-epithelization and weak to moderate positive VEGF immunoreactions.Whereas, groups treated with atorvastatin or ADSCs exhibited better healing of the wound. However ADSCs group (V) showed better organization of collagen together with reappearance of skin appendages which were missed in atorvastatin group (VI). Conclusion: Both atorvastatin and ADSCs proved a definite ameliorating effect on the wound healing of diabetic rats. However, ADSCs administration denoted a more remarkable therapeutic healing effect compared to Atorvastatin.

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Section: Discussionmentioning

confidence: 99%

A Histological and Immuno-histchemical study on the Effect of Atorvastatin versus Adipose Derived Stem Cells on Cutaneous Wound Healing in Diabetic Male Albino Rats

Elmohsen

Salama

Abdelaziz

et al. 2020

Egyptian Journal of Histology

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“…Histone acetylation and deacetylation are catalyzed by HATs and HDACs. Accumulating evidence suggests that reduced histone acetylation is associated with increased histone deacetylase (HDAC) and plays an important role in the pathogenesis of many complex human diseases 18–24 .…”

Section: Discussionmentioning

confidence: 99%

“…Notably, decreased histone acetylation can be restored or upregulated by the application of HDAC inhibitors (HDACis). Research has shown that HDACis can be used to treat numerous clinical diseases in human and animal models, including inflammation, angiogenesis, tumorigenesis, aging, degenerative diseases and regeneration 18–24 . Interestingly, inhibition of histone deacetylation as novel anti-fungal therapy has been shown to be an option in the treatment of fungal infection 25 , However, the effect of the HDAC inhibitors on the experimental fungal keratitis has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitor attenuates experimental fungal keratitis in mice

Yuan

Yin

et al. 2019

Sci Rep

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Fungal keratitis is one of the leading causes of blindness of infected corneal diseases, but the pathogenesis of fungal keratitis is not fully understood and therefore the treatment of the disease by medication is still under investigation. In the current study, we sought to study the effect of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on experimental fungal keratitis in mice. SAHA (25 mg/kg) (n = 30) or vehicle (DMSO) (n = 30) was delivered through intraperitoneal injection (IP) 24 hours after the fungal inoculation, and the same amount of SAHA injection or DMSO was followed at day 2. The expression of histone H3 (H3), acetylated histone H3 (AC-H3), histone deacetylase 1 (HDAC)1, tumor necrosis factor-α (TNFα), and Toll-like receptor 4 (TLR4) in surgically excised specimens from the patients and mice with fungal keratitis were detected by immunohistochemistry. The expression of mRNAs for Interleukin-1β (IL-1β), TNFα, and TLR4 were evaluated in the corneas of the mice with fungal infection and the control corneas by real-time PCR. The quantification of IL-1β and TNFα in the corneas of the mice with fungal infection was determined by ELISA. The inhibitory effect of SAHA on mice fungal keratitis was revealed by GMS and H&E staining. We found that the downregulation of histone acetylation and upregulation of HDAC1 expression were associated with the increased inflammation response in fungal keratitis not only in humans but also in experimental animals. SAHA was able to inhibit experimental fungal keratitis in mouse by suppressing TLR4 and inflammatory cytokines such as TNFα and IL-1β; the inhibition of HDAC may be a potential therapeutic approach for the treatment of fungal keratitis.

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“…Omentum lacking areas of sizeable tumor implants was used to isolate OASC‐M. Adipose‐derived stem cells isolation and cell culture was performed as previously described by Koko et al . The stromal vascular fraction (SVF) initial cell count was performed using an automated cell counter (NucleoCounter NC‐200; ChemoMetec, NY, USA) and plated at 1 × 10 6 cells per T75 flask.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic therapy can inhibit growth of ovarian cancer cells and reverse chemoresistant properties acquired from metastatic omentum

Sookram

Zheng

Linden

et al. 2019

Intl J Gynecology & Obste

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Objective To examine the cytotoxicity of epigenetic drugs independently and in combination with chemotherapy on ovarian cancer cells Caov‐3, and to investigate their ability to acquire chemoresistance in omental microenvironments and whether epigenetic drugs can counteract this chemoresistance. Methods A pilot study was conducted in Cooper University Hospital, NJ, USA from August 1 to October 31, 2017, among women undergoing surgeries for uterine and ovarian cancer. Cytotoxicity assays using IC50 values of epigenetic drugs and paclitaxel and cisplatin were performed on Caov‐3. Omental adipose‐derived stem cells (OASCs) were isolated from omentum with/without metastases. Caov‐3 was cultured with OASCs’ conditioned medium and subjected to different drugs. Cell viability and secretome was measured using MTT and Elisa, respectively. Results Three women met the eligibility criteria and were included in the study. Epigenetic drugs alone or in combination with chemotherapy showed 85%–94% increased cytotoxicity against Caov‐3 (P≤0.005). Metastatic OASCs conditioned medium showed up to 27‐fold increase in tumorigenic factors and promoted chemoresistance (28%–35%; P < 0.050) against chemotherapy. Epigenetic therapy resulted in up to a 40‐fold reversal in this chemoresistance. Conclusion Epigenetic therapies could have an important role in treating a subgroup of ovarian cancer patients that demonstrate resistance to first‐line chemotherapy.

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Histone Deacetylase Inhibitors Enhance Cytotoxicity Towards Breast Tumors While Preserving the Wound-Healing Function of Adipose-Derived Stem Cells

Cited by 9 publications

References 46 publications

A Histological and Immuno-histchemical study on the Effect of Atorvastatin versus Adipose Derived Stem Cells on Cutaneous Wound Healing in Diabetic Male Albino Rats

A Histological and Immuno-histchemical study on the Effect of Atorvastatin versus Adipose Derived Stem Cells on Cutaneous Wound Healing in Diabetic Male Albino Rats

Histone deacetylase inhibitor attenuates experimental fungal keratitis in mice

Epigenetic therapy can inhibit growth of ovarian cancer cells and reverse chemoresistant properties acquired from metastatic omentum

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