scholarly journals Mathematical model of STAT signalling pathways in cancer development and optimal control approaches

2021 ◽  
Vol 8 (9) ◽  
Author(s):  
Jonggul Lee ◽  
Donggu Lee ◽  
Yangjin Kim
Keyword(s):  
Mathematical Model ◽  
Optimal Control ◽  
Cell Death ◽  
Cancer Cells ◽  
Tumour Volume ◽  
Intracellular Signalling ◽  
Mathematical Framework ◽  
Administrative Costs ◽  
Signalling Network ◽  
Cell Death Program

In various diseases, the STAT family display various cellular controls over various challenges faced by the immune system and cell death programs. In this study, we investigate how an intracellular signalling network (STAT1, STAT3, Bcl-2 and BAX) regulates important cellular states, either anti-apoptosis or apoptosis of cancer cells. We adapt a mathematical framework to illustrate how the signalling network can generate a bi-stability condition so that it will induce either apoptosis or anti-apoptosis status of tumour cells. Then, we use this model to develop several anti-tumour strategies including IFN-β infusion. The roles of JAK-STATs signalling in regulation of the cell death program in cancer cells and tumour growth are poorly understood. The mathematical model unveils the structure and functions of the intracellular signalling and cellular outcomes of the anti-tumour drugs in the presence of IFN-β and JAK stimuli. We identify the best injection order of IFN-β and DDP among many possible combinations, which may suggest better infusion strategies of multiple anti-cancer agents at clinics. We finally use an optimal control theory in order to maximize anti-tumour efficacy and minimize administrative costs. In particular, we minimize tumour volume and maximize the apoptotic potential by minimizing the Bcl-2 concentration and maximizing the BAX level while minimizing total injection amount of both IFN-β and JAK2 inhibitors (DDP).

scholarly journals The “ARTS” of Cell Death in Service of Life: How Do We Force Cancer Cells to Commit Suicide?

2021 ◽  
Vol 9 ◽  
Author(s):  
Sarit Larisch
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Novel Therapy ◽  
The Arts ◽  
Wide Range ◽  
Cell Death Program ◽  
Cancerous Cells ◽  
Critical Process ◽  
Cells Death ◽  
Commit Suicide

Every cell in our body contains a “self-destruction” program. This cell death is a critical process allowing replacement of damaged cells with healthy ones to prevent wide range of diseases. When the cell’s death mechanism gets “stuck” and is not activated, cancer can result. In healthy cells there is a balanced system of proteins, some of which activate the normal death mechanism, and some of which inhibit this process. This is like the system of gas and brakes in a car. Researchers have found that cancer cells lack a protein, called ARTS, which is crucial for activating the cells’ death mechanism. The lack of ARTS causes cancer cells to escape death and become “immortal.” Small ARTS-like molecules have been discovered that can penetrate cancerous cells and reactivate the cell death program, effectively making the cancer cells “commit suicide.” We envision that these ARTS-like molecules will provide novel therapy for cancer.

scholarly journals Future Therapeutic Directions for Smac-Mimetics

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 406 ◽  
Author(s):  
Emma Morrish ◽  
Gabriela Brumatti ◽  
John Silke
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Inhibitor Of Apoptosis ◽  
Growth Strategies ◽  
Promote Tumor Growth ◽  
Cell Death Program ◽  
Smac Mimetics ◽  
Promote Cell Death

It is well accepted that the ability of cancer cells to circumvent the cell death program that untransformed cells are subject to helps promote tumor growth. Strategies designed to reinstate the cell death program in cancer cells have therefore been investigated for decades. Overexpression of members of the Inhibitor of APoptosis (IAP) protein family is one possible mechanism hindering the death of cancer cells. To promote cell death, drugs that mimic natural IAP antagonists, such as second mitochondria-derived activator of caspases (Smac/DIABLO) were developed. Smac-Mimetics (SMs) have entered clinical trials for hematological and solid cancers, unfortunately with variable and limited results so far. This review explores the use of SMs for the treatment of cancer, their potential to synergize with up-coming treatments and, finally, discusses the challenges and optimism facing this strategy.

scholarly journals Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells

Oncogene ◽  
1999 ◽  
Vol 18 (13) ◽  
pp. 2281-2290 ◽  
Author(s):  
Shunji Chi ◽  
Chifumi Kitanaka ◽  
Kohji Noguchi ◽  
Toshihiro Mochizuki ◽  
Yohji Nagashima ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Oncogenic Ras ◽  
Cell Death Program ◽  
Cell Suicide

BAMLET Activates a Lysosomal Cell Death Program in Cancer Cells

2010 ◽  
Vol 9 (1) ◽  
pp. 24-32 ◽  
Author(s):  
Paul Rammer ◽  
Line Groth-Pedersen ◽  
Thomas Kirkegaard ◽  
Mads Daugaard ◽  
Anna Rytter ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cell Death Program

Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

2013 ◽  
Vol 3 (3) ◽  
pp. 66 ◽  
Author(s):  
Vanessa Hörmann ◽  
Sivanesan Dhandayuthapani ◽  
James Kumi-Diaka ◽  
Appu Rathinavelu
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Treatment Options ◽  
Attractive Alternative ◽  
Intrinsic Apoptotic Pathway ◽  
Prostate Cancer Cells ◽  
Apoptotic Pathway ◽  
Combination Treatments

Background: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments. Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency) at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i) growth inhibition through trypan blue exclusion assay and microphotography, ii) classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii) activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients. Key words: topotecan; genistein; intrinsic apoptotic cell death

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