scholarly journals Promising activity against NTERA-2 cancer stem cells of malloapelta B compound isolated from the Bum-bup plant in Vietnam

2020 ◽  
Vol 18 (1) ◽  
pp. 117-125
Author(s):  
Do Thi Thao ◽  
Nguyen Thi Nga ◽  
Nguyen Thi Cuc ◽  
Do Thi Phuong ◽  
Trieu Ha Phuong ◽  
...  

Recent studies have revealed that cancer stem cells (CSCs) drive tumor growth, metastasis, therapy resistant and recurrence. Therefore, CSCs are considered as new targets for screening of more effective drugs. The compound malloapelta B, which was isolated from the Bum-bup plant (Mallotus apelta) (Lour.) Muel.-Arg, Euphorbiaceae) in Vietnam, presented very potent and strong anticancer invitro, especially against the activation ofNF-kB (nuclear factor- kappa B). In our research, malloapelta B inhibited the growth of NTERA-2 line, a CSC line, at the value of IC50 = 12.71 ± 0.76 µM. In this study, malloapelta B also had effects on cell cycle of NTERA-2 by significantly reducing the cell number at G0/G1 phase (37.48%), while raising this number of phase G2/M to 31.12% in comparison with those of control (56.81% and 18.6%, respectively). Besides, clonogenic and tumorspheroidal formations are acknowledged as typically renewable characteristics of CSCs. Then, in our studies, malloapelta B significantly prevented NTERA-2 to form clonogens and reduced tumorspheres’ sizes at treatments with 20 and 100 µg/mL. However, malloapelta B did not exhibit any obvious effects on the expression level of CD44+/CD24+, the two typical cell surface markers of CSCs, at 2.5 and 5 µM treatments.

2020 ◽  
Author(s):  
Lucía Benítez ◽  
Lucas Barberis ◽  
Luciano Vellón ◽  
Carlos Alberto Condat

Abstract Background: Cancer stem cells are important for the development of many solid tumors. These cells receive promoting and inhibitory signals that depend on the nature of their environment (their niche) and determine cell dynamics. Mechanical stresses are crucial to the initiation and interpretation of these signals. Methods: A two-population mathematical model of tumorsphere growth is used to interpret the results of a series of experiments recently carried out in Tianjin, China, and extract information about the intraspecific and interspecific interactions between cancer stem cell and differentiated cancer cell populations. Results: The model allows us to reconstruct the time evolution of the cancer stem cell fraction, which was not directly measured. We find that, in the presence of stem cell growth factors, the interspecific cooperation between cancer stem cells and differentiated cancer cells induces a positive feedback loop that determines growth, independently of substrate hardness. In a frustrated attempt to reconstitute the stem cell niche, the number of cancer stem cells increases continuously with a reproduction rate that is enhanced by a hard substrate. For growth on soft agar, intraspecific interactions are always inhibitory, but on hard agar the interactions between stem cells are collaborative while those between differentiated cells are strongly inhibitory. Evidence also suggests that a hard substrate brings about a large fraction of asymmetric stem cell divisions. In the absence of stem cell growth factors, the barrier to differentiation is broken and overall growth is faster, even if the stem cell number is conserved. Conclusions: Our interpretation of the experimental results validates the centrality of the concept of stem cell niche when tumor growth is fueled by cancer stem cells. Niche memory is found to be responsible for the characteristic population dynamics observed in tumorspheres. A specific condition for the growth of the cancer stem cell number is also obtained.


2012 ◽  
Vol 227 (6) ◽  
pp. 2686-2693 ◽  
Author(s):  
Alba Rocco ◽  
Eleonora Liguori ◽  
Giuseppe Pirozzi ◽  
Virginia Tirino ◽  
Debora Compare ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Martin H. Maurer

Mesenchymal stem cells (MSCs) are pluripotent cells isolated from the bone marrow and various other organs. They are able to proliferate and self-renew, as well as to give rise to progeny of at least the osteogenic, chondrogenic, and adipogenic lineages. Despite this functional definition, MSCs can also be defined by their expression of a distinct set of cell surface markers. In the current paper, studies investigating the proteome of human MSCs are reviewed with the aim to identify common protein markers of MSCs. The proteomic analysis of MSCs revealed a distinct set of proteins representing the basic molecular inventory, including proteins for (i) cell surface markers, (ii) the responsiveness to growth factors, (iii) the reuse of developmental signaling cascades in adult stem cells, (iv) the interaction with molecules of the extracellular matrix, (v) the expression of genes regulating transcription and translation, (vi) the control of the cell number, and (vii) the protection against cellular stress.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13030-e13030
Author(s):  
Soma Mukhopadhyay ◽  
Sudeshna Gangopadhyay ◽  
Swati Dasgupta ◽  
Saubhik Sengupta ◽  
Ujjal Kanti Ray ◽  
...  

e13030 Background: Simple BRCA screening is insufficient for ‘event-free survival’ as breast cancer is clinically and pathologically an extremely heterogeneous disease. Targeting Breast Cancer Stem Cells (BCSCs) present in bone marrow and breast tissues is a lucrative alternative. Identification of BCSCs is salient aspect of our research. Invasive and mesenchymal property of BCSCs with CD44+/CD24low/ALDH1+ phenotype has made them a promising target for eliminating metastatic capacity of primary tumors. We hypothesize that ability to therapeutically attack stem cell hinges upon identifying unique targets like cell surface markers and this will decide development of specific target therapies. Methods: A total of 10 early chemo-naive patients with biopsy proven triple-negative metastatic breast cancer in the age group of 18-36 yr.s (mean age 28 yr.s) were selected randomly and tested for CD44/CD24 cell surface markers following immunosorting using magnetic cell sorter and immunophenotyping by flowcytometric analysis. Isolated BCSCs were cultured for in vitro drug sensitivity towards platinum, anthracycline and docetaxel. Correlation was drawn between cell differentiation, % of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. % of BCSCs in pre- and post-chemotherapeutic condition was further compared. Results: We have detected BCSCs in 90% of cases. Among positive samples, 89% patients showed platinum sensitivity and rest were found to be anthracycline sensitive. No sensitivity to docetaxel was observed. In lieu of this, cisplatin was applied in vivo and % of BCSCs came down to 6.58% from initial 11.16% (for a representative case). Conclusions: Thus primary aim to target BCSCs at the onset of tumors in breast cancer patients to control metastasis and relapse of disease was somewhat obtained. We further plan to correlate ratio of selected markers present in patients in pre- and post-chemotherapeutic condition with time to recurrence, mortality, morbidity and progression-free survival. Finally, if no BCSCs prevail after chemotherapy, then patients would be kept under observation and if traces are found, we would proceed to targeted therapy trial like PARP inhibitor or autologous stem cell replacement.


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 376
Author(s):  
Monica Marzagalli ◽  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Patrizia Limonta

Tumor relapse and treatment failure are unfortunately common events for cancer patients, thus often rendering cancer an uncurable disease. Cancer stem cells (CSCs) are a subset of cancer cells endowed with tumor-initiating and self-renewal capacity, as well as with high adaptive abilities. Altogether, these features contribute to CSC survival after one or multiple therapeutic approaches, thus leading to treatment failure and tumor progression/relapse. Thus, elucidating the molecular mechanisms associated with stemness-driven resistance is crucial for the development of more effective drugs and durable responses. This review will highlight the mechanisms exploited by CSCs to overcome different therapeutic strategies, from chemo- and radiotherapies to targeted therapies and immunotherapies, shedding light on their plasticity as an insidious trait responsible for their adaptation/escape. Finally, novel CSC-specific approaches will be described, providing evidence of their preclinical and clinical applications.


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