Curcumin in combination with homoharringtonine suppresses lymphoma cell growth by inhibiting the TGF-β/Smad3 signaling pathway

Xiang, Jingjing; Zhu, Ni; Ge, Hangping; Sheng, Xianfu; Deng, Shu; Chen, Junfa; Yu, Lei; Zhou, Yan; Shen, Jianping

doi:10.18632/aging.203319

Cited by 7 publications

(6 citation statements)

References 45 publications

(42 reference statements)

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“…Here we detected that the activator (procaspase-9) and executioner (procaspase-3 and procaspase-7) were upregulated in a permissive temperature group but show a differential pattern when cells are cultured at the non-permissive temperature. When mitochondrial-mediated apoptosis is induced and caspase-9 and caspase-3 are activated, the expression of Bax and Bcl-2 has been reported to show different levels to maintain their balance ( Zhang et al, 2021 ). Irradiation-induced senescence is accompanied by an upregulation of procaspase-3, -7, and -9 ( Chang et al, 2016 ; Baar et al, 2017 ) but a downregulation of activated caspase-3 ( Chang et al, 2016 ), in line with our results.…”

Section: Discussionmentioning

confidence: 99%

A Human Conditionally Immortalized Proximal Tubule Epithelial Cell Line as a Novel Model for Studying Senescence and Response to Senolytics

et al. 2022

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Accumulating evidence suggests that senescence of kidney tubule epithelial cells leads to fibrosis. These cells secrete senescence-associated secretory phenotype (SASP) factors that are involved in diverse signaling pathways, influencing kidney fibrosis. Here, we investigated whether our previously established conditionally immortalized proximal tubule epithelial cell line overexpressing the organic anion transporter 1 (ciPTEC-OAT1) can be used as a valid in vitro model to study kidney senescence and senolytics response. CiPTEC-OAT1 proliferates rapidly at 33°C and exhibits a “senescence-like” arrest at 37°C, most likely due to suppression of SV40T expression and subsequent reactivation of the p53 and Rb pathways. To understand how permissive (33°C) and non-permissive (37°C) temperatures of the cell culture affect the senescence phenotype, we cultured ciPTEC-OAT1 for up to 12 days and evaluated the apoptosis and SASP markers. Day 0 in both groups is considered as the non-senescence group (control). Further, the potential of navitoclax, dasatinib, quercetin, and the combination of the latter two to clear senescent cells was evaluated. Maturation of ciPTEC-OAT1 at non-permissive temperature affected mRNA and protein levels of senescence markers. A remarkable upregulation in p21 gene expression was found in the non-permissive temperature group, whereas expression of Lamin B1 decreased significantly. SASP factors, including PAI-1A, IL-1β, CTGF, and IL-6 were upregulated, but no significant difference in Bcl-2 and Bcl-xl were found in the non-permissive temperature group. After culturing ciPTEC-OAT1 up to 12 days, cells in the non-permissive temperature group showed an upregulation in the apoptosis-associated proteins Bcl-2, BID, and Bax, and a downregulation in Mcl-1, Bad, Bak, and Bim at various time points. Further, Bcl-xl, Puma, Caspase 3, Caspase 7, and Caspase 9 showed initial upregulations followed by downregulations at later time points. The loss of Lamin B1, upregulation of SA-β-gal expression and increase in its activity, upregulation of p21 levels and downregulation of p53, along with the upregulation of SASP factors, confirmed that maturation at 37°C promotes senescence features. Finally, the senolytics response was evaluated by testing cell viability following exposure to senolytics, to which cells appeared dose-dependently sensitive. Navitoclax was most effective in eliminating senescent cells. In conclusion, culturing ciPTEC-OAT1 at 37°C induces a senescence phenotype characterized by increased expression of cell cycle arrest and anti-apoptosis markers, SASP factors, and responsiveness to senolytics treatment. Therefore, ciPTEC-OAT1 represents a valid model for studying kidney senescence by simply adjusting culture conditions.

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Section: Discussionmentioning

confidence: 99%

A Human Conditionally Immortalized Proximal Tubule Epithelial Cell Line as a Novel Model for Studying Senescence and Response to Senolytics

et al. 2022

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“…Here we detected that the activator (procaspase-9) and executioner (procaspase-3 and procaspase-7) were upregulated at permissive temperature, but showed a differential pattern when cells were cultured at non-permissive temperature. When mitochondrial-mediated apoptosis is induced and caspase-9 and caspase-3 are activated, the expression of Bax and Bcl-2 has been reported to show different levels to maintain their balance (Zhang et al, 2021). Irradiation-induced senescence is accompanied by an upregulation of procaspase-3, -7 and -9 but a downregulation of activated caspase-3 , in line with our results.…”

Section: Discussionsupporting

confidence: 91%

Senescent cell accumulation & Research-based undergraduate education

Valentijn¹

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Chapter 1 General introduction Chapter 2 Cellular senescence in the aging and diseased kidney Chapter 3 CCN2 aggravates acute DNA damage and the subsequent DDR-Senescence-Fibrosis sequence following renal ischemiareperfusion injury Chapter 4 CCN2 aggravates the immediate Oxidative Stress-DNA Damage Response following renal ischemia-reperfusion injury Chapter 5 Acute kidney injury is aggravated in aged mice by the exacerbation of proinflammatory processes Chapter 6 Oxidative stress and cellular senescence are involved in the aging kidney Chapter 7 A human conditionally immortalized proximal tubule epithelial cell line as a novel model for studying senescence and response to senolytics Chapter 8 Cellular senescence and the kidney: potential therapeutic targets and tools Chapter 9 Cellular senescence in kidney biopsies is associated with tubular dysfunction and predicts CKD progression in childhood cancer patients with KIN Bridging research (part 1) and education (part 2) Chapter 10 Proposal for a research-based bachelor course design to provide insight into underlying mechanisms of the rare, genetic renal disease KIN Part 2. Research-based education in undergraduate biomedicine education Chapter 11 A challenge-based interdisciplinary undergraduate concept fostering translational medicine Chapter 12 A novel undergraduate biomedical laboratory course concept in synergy with ongoing faculty research Chapter 13 Hybrid PhD tracks with synergy between education and research Chapter 14 Summarizing discussion and future perspectives Appendices Nederlandse samenvatting Dankwoord Curriculum vitae CHAPTER 1 General introductionChapter 1. General introduction Chronic kidney disease is a major health burden lacking effective treatment Chronic kidney disease (CKD) is a common, progressive and irreversible disorder. In 2016, the global prevalence of CKD was estimated to be 13.4%. In the Netherlands, the prevalence of CKD is estimated to be around 10%. (Nierstichting-a) People with CKD have an increased risk of end-stage kidney disease (ESKD) and cardiovascular disease. Lifestyle and drug interventions (e.g. ACE inhibition or angiotensin II receptor type 2 inhibition) are currently the cornerstone for treatment for CKD, but do not sufficiently prevent CKD progression. A large number of CKD patients (approximately 2000 patients per year in the Netherlands (Nierstichting-b)) develop ESKD and will need to switch to renal replacement therapy such as dialysis or transplantation. During dialysis, quality of life is poor and morbidity and mortality are high. ESRD patients who start dialysis between the ages of 45 and 65 have a 5-year survival rate of under 50% in the United States and Europe. (Robinson et al. 2016) Donor kidneys are scarce and long-term renal allograft survival is poor. The halflife of kidney transplants is approximately 9 years for deceased donor grafts and 12 years for living donor grafts. (Lamb et al. 2011) Thus, the demand for better treatment options to stop CKD progression and improve survival of a graft kidney i...

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“…We found that the main signaling pathway of this gene is PI3K / AKT / mTOR, and the activation of this pathway is also the main driving force for poor prognosis in lymphoma. In addition to drug inhibition, TGF-signaling was found to inhibit lymphoma growth in a variety of lymphomas(natural killer/ T cell lymphoma, diffuse large B-cell lymphoma), and repeated inactivation occurred in these lymphomas [23,24,25].…”

Section: Discussionmentioning

confidence: 99%

Revealing the clinical impact of MTOR and ARID2 gene mutations on MALT lymphoma of the alimentary canal using targeted sequencing

Huang

Luo

et al. 2022

Preprint

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Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are a group of diseases with marked heterogeneity, including clinical, immunohistochemical, and molecular heterogeneity. The disease remains unspecified in the genetic landscape with only a few sequencing studies to date; however, systematic studies of alimentary canal MALT lymphoma have not been reported. To better understand the genetics of this tumor, targeted sequencing in a group of 31 cases (including 2 esophageal, 2 colonic, 4 small intestinal, and 23 gastric cases) were performed. We found epigenetic regulation (DNMT3A, KMT2D, KMT2A, EP300, TET2, etc.), signaling pathways (APC, CHD8, TNFAIP3, TNFRSF14, ZAP70, NF1,), and tumor suppressor genes (TP53, BCORL1, FOXO1, ATM, etc.) involved. Moreover, we found MTOR gene mutations in 16% of the cases that made these patients more prone to recurrence and metastasis than those with MTOR wild type genes. More interestingly, ARID2 mutations were detected in 32% of all the cases, and the mutation rate was higher and statistically significant in Helicobacter pylori (Hp)-negative patients in the gastric group. Therefore, this study found that MTOR and ARID2 gene mutations have pathogenic and prognostic implications.

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Curcumin in combination with homoharringtonine suppresses lymphoma cell growth by inhibiting the TGF-β/Smad3 signaling pathway

Cited by 7 publications

References 45 publications

A Human Conditionally Immortalized Proximal Tubule Epithelial Cell Line as a Novel Model for Studying Senescence and Response to Senolytics

A Human Conditionally Immortalized Proximal Tubule Epithelial Cell Line as a Novel Model for Studying Senescence and Response to Senolytics

Senescent cell accumulation & Research-based undergraduate education

Revealing the clinical impact of MTOR and ARID2 gene mutations on MALT lymphoma of the alimentary canal using targeted sequencing

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