Dose and drug changes in chronic lymphocytic leukemia cell response in�vitro: A comparison of standard therapy regimens with two novel cyclin‑dependent kinase inhibitors

Kubczak, Małgorzata; Szustka, Aleksandra; Błoński, Jerzy Z.; Gucký, Tomáš; Misiewicz, Małgorzata; Kryštof, Vladimír; Robak, Paweł; Rogalińska, Małgorzata

doi:10.3892/mmr.2019.10007

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…In lower concentration, it can protect neurons from apoptosis (Figures 2 and 3). Quercetin was also able to induce caspase-dependent apoptosis through an inhibition of activator of transcription and HER2 overexpression in BT-474 breast cancer cells [167][168][169][170]. Additionally, other data suggest that quercetin can also inhibit PI3K/AKT, Wnt/β-catenin and STAT3 pathways (Figure 2) [159].…”

Section: Quercetinmentioning

confidence: 90%

Molecular Targets of Natural Compounds with Anti-Cancer Properties

Kubczak

Szustka

Rogalińska

2021

IJMS

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Cancer is the second leading cause of death in humans. Despite rapid developments in diagnostic methods and therapies, metastasis and resistance to administrated drugs are the main obstacles to successful treatment. Therefore, the main challenge should be the diagnosis and design of optimal therapeutic strategies for patients to increase their chances of responding positively to treatment and increase their life expectancy. In many types of cancer, a deregulation of multiple pathways has been found. This includes disturbances in cellular metabolism, cell cycle, apoptosis, angiogenesis, or epigenetic modifications. Additionally, signals received from the microenvironment may significantly contribute to cancer development. Chemical agents obtained from natural sources seem to be very attractive alternatives to synthetic compounds. They can exhibit similar anti-cancer potential, usually with reduced side effects. It was reported that natural compounds obtained from fruits and vegetables, e.g., polyphenols, flavonoids, stilbenes, carotenoids and acetogenins, might be effective against cancer cells in vitro and in vivo. Several published results indicate the activity of natural compounds on protein expression by its influence on transcription factors. They could also be involved in alterations in cellular response, cell signaling and epigenetic modifications. Such natural components could be used in our diet for anti-cancer protection. In this review, the activities of natural compounds, including anti-cancer properties, are described. The influence of natural agents on cancer cell metabolism, proliferation, signal transduction and epigenetic modifications is highlighted.

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Section: Quercetinmentioning

confidence: 90%

Molecular Targets of Natural Compounds with Anti-Cancer Properties

Kubczak

Szustka

Rogalińska

2021

IJMS

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“…CDK1 modulation may therefore represent a novel therapeutic approach for CLL. However, CDKs inhibitors have severe side effects such as tumor lysis syndrome, secretory diarrhea, and other [21]. and their clinical use should be performed by experienced haematologists.…”

Section: Introductionmentioning

confidence: 99%

Indirubin in Vitro Apoptotic Effect Towards Chronic Lymphocytic Leukaemia (CLL) Lineage

Jafarinejad,

Yarmohammadi,

Piccin

et al. 2023

Preprint

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Chronic lymphocytic leukemia (CLL) is a chronic condition that usually affects elderly people. The etiology is unknown, however the current hypothesis is that over time the haematopoietic stem cells may acquire mutations that will lead to irregularity in apoptotic mechanism (e.g. BCL2 mutation). Dangui Luhui Wan consist in mix of 11 herbs used by the Chinese Medicine. This herbal compound has proven to have antitumoral activities on various types of cancer cells. A derivate from Dangui Luhui Wan is indirubin-3'-monoxime (I3M). This substance act as selective inhibitor of cyclin-dependent kinases (CDKs) and can induce cell apoptosis. The aim of this study was to test the efficacy of I3M against CLL cells in vitro. We evaluated the expression of apoptotic proteins Bcl2/Bax and CDK1/2 using real-time PCR. Peripheral mononuclear cells (PBMCs) obtained from 14 patients were treated with 20 μM of I3M for 48hrs. After treatment a reduced Bcl-2 expression was noticed. No significant changes were seen for Bax. However, an increased Bax/Bcl-2 ratio was documented, suggesting that mitochondrial pathway is involved in I3M apoptotic-mechanism of action. Interestingly, I3M could inhibit the expression of CDK2, while it does not affect the expression of CDK1. These results indicated that I3M exerts anti-tumor effects through induction apoptosis and inhibition of CDK2. Further studies are now needed to clarify the exact mechanism of action of I3M in CLL and possibly in other tumoral cell lines.

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“…Moreover, during leukemic cell incubation with drugs, we are able to check also patients' cell sensitivity to in vitro incubation conditions. If in control untreated cells, cell viability decreases similarly like in treated ones, it is an indication that patient might need a reduction in drug dose in vivo [15]. Moreover, we need more knowledge on this topic to be able precisely to transform drug doses obtained in patient's blood into in vitro conditions.…”

Section: Introductionmentioning

confidence: 99%

New Perspectives in Personalization of Therapy for Hematological Cancers

Rogalińska¹

2021

Methods in Molecular Medicine

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A progress in treatment of hematological cancers was achieved. Unfortunately, some youngsters, because of rare genetic alterations that are not easy to detect, as well as heavily pretreated old patients, because of coexisting diseases that lead to changes in patient metabolism, do not respond to therapy. Moreover, sometimes familiar diversities and alterations on genetic or epigenetic level that could be transferred on diversities in metabolism or cell signaling might be a reason why patients do not respond to therapy. Interestingly, for older patients a resistance to therapy could also occur as a reason of drug cross-reactivity. For designing of effective anticancer therapy for patient with chronic lymphocytic leukemia before drug administration, patient's leukemic cell response to anticancer drug(s) should be checked. Moreover, for patient response to treatment, also drugs prescribed previously by other medical doctors or even patients' diet could be important for achieving therapeutic success of therapy. Therefore it is important to choose the effective drugs before their administration to patient that will improve treatment efficacy and exclude resistance to therapy. It must be stated that the special attention for personalized therapy tests should be focused on patients previously resistant to therapy, more sensitive to drugs or heavily pretreated.

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Dose and drug changes in chronic lymphocytic leukemia cell response in�vitro: A comparison of standard therapy regimens with two novel cyclin‑dependent kinase inhibitors

Cited by 4 publications

References 37 publications

Molecular Targets of Natural Compounds with Anti-Cancer Properties

Molecular Targets of Natural Compounds with Anti-Cancer Properties

Indirubin in Vitro Apoptotic Effect Towards Chronic Lymphocytic Leukaemia (CLL) Lineage

New Perspectives in Personalization of Therapy for Hematological Cancers

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