BTYNB, an inhibitor of RNA binding protein IGF2BP1 reduces proliferation and induces differentiation of leukemic cancer cells

Jamal, Alam; Dalhat, Mahmood Hassan; Jahan, Sadaf; Choudhry, Hani; Khan, Mohammad Imran

doi:10.1016/j.sjbs.2023.103569

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…The target cells were subjected to a flow cytometry analysis for the determination of the distribution of the cells across the different phases of the cell cycle. The cell cycle assay was conducted with a sample size of 10,000 cells per event, in triplicate, using an Amnis flow cytometer [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

A comparative <i>in vitro</i> study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

KARIM,

ALGHANMI,

JAMAL

et al. 2024

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Cancer frequently develops resistance to the majority of chemotherapy treatments. This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors, specifically Canagliflozin (CAN), Dapagliflozin (DAP), Empagliflozin (EMP), and Doxorubicin (DOX), using in vitro experimentation. The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin (DOX) in MCF-7 cells. Interestingly, it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth. Notably, when these medications were combined with DOX, there was a considerable inhibition of glucose consumption, as well as reductions in intracellular ATP and lactate levels. Moreover, this effect was found to be dependent on the dosages of the drugs. In addition to effectively inhibiting the cell cycle, the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression. This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications, namely CAN, DAP, and EMP, on the responsiveness to the anticancer properties of DOX. The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

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Section: Methodsmentioning

confidence: 99%

A comparative <i>in vitro</i> study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

KARIM,

ALGHANMI,

JAMAL

et al. 2024

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“…195 Testing on leukaemic cells showed decreased cell viability, increased cell death, and cell cycle arrest at S-phase. 196 In vivo, BTYNB shows promising anti-tumour efficacy in xenograft models of intrahepatic cholangiocarcinoma and ovarian cancer. 197,198 CuB, identified from HTS of 889 compounds from the Medicinal Natural Products Library, allosterically binds IGF2BP1, altering expression of downstream RNA such as c-MYC, Kras, and FSCN1.…”

Section: Alkbh5 Inhibitorsmentioning

confidence: 99%

“…It also impairs cell proliferation and induces apoptosis in Neuroendocrine Neoplasm (NEN) cells 195 . Testing on leukaemic cells showed decreased cell viability, increased cell death, and cell cycle arrest at S‐phase 196 . In vivo, BTYNB shows promising anti‐tumour efficacy in xenograft models of intrahepatic cholangiocarcinoma and ovarian cancer 197,198 …”

Section: Therapeutic Potentialmentioning

confidence: 99%

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

Guan,

Wong

2024

Cancer Medicine

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The N6‐methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising RNA methylation have been identified. Notably, these m6A regulators often exhibit altered expression patterns in cancer, occasionally offering prognostic value. Nonetheless, the complex roles of these regulators in human cancer pathology remain enigmatic, with conflicting outcomes reported in different studies.In recent years, a multitude of inhibitors and activators targeting m6A regulators have been reported. Several of these compounds have demonstrated promising efficacy in both in vitro and in vivo cancer models. These findings collectively underscore the dynamic landscape of m6A regulation in cancer biology, revealing its potential as a therapeutic target and prognostic indicator.

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“…Small-molecule inhibitors of IGF2BP1 and IGF2BP3 are at the preclinical stage. BTYNB destabilizes oncogenic transcripts by disrupting the IGF2BP1–mRNA association ( Müller et al, 2020 ; Jamal et al, 2023 ; Sharma et al, 2023 ). Combining menin inhibitors with depletion of IGF2BP3 impairs cell growth and increases differentiation of KMT2A::AFF1 leukemia ( Lin et al, 2023 ).…”

Section: Targeting Aberrant Stem Cell Programs In Leukemia For Therapymentioning

confidence: 99%

Aberrant stem cell and developmental programs in pediatric leukemia

Ling,

Cross,

Roy

2024

Front. Cell Dev. Biol.

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Hematopoiesis is a finely orchestrated process, whereby hematopoietic stem cells give rise to all mature blood cells. Crucially, they maintain the ability to self-renew and/or differentiate to replenish downstream progeny. This process starts at an embryonic stage and continues throughout the human lifespan. Blood cancers such as leukemia occur when normal hematopoiesis is disrupted, leading to uncontrolled proliferation and a block in differentiation of progenitors of a particular lineage (myeloid or lymphoid). Although normal stem cell programs are crucial for tissue homeostasis, these can be co-opted in many cancers, including leukemia. Myeloid or lymphoid leukemias often display stem cell-like properties that not only allow proliferation and survival of leukemic blasts but also enable them to escape treatments currently employed to treat patients. In addition, some leukemias, especially in children, have a fetal stem cell profile, which may reflect the developmental origins of the disease. Aberrant fetal stem cell programs necessary for leukemia maintenance are particularly attractive therapeutic targets. Understanding how hijacked stem cell programs lead to aberrant gene expression in place and time, and drive the biology of leukemia, will help us develop the best treatment strategies for patients.

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BTYNB, an inhibitor of RNA binding protein IGF2BP1 reduces proliferation and induces differentiation of leukemic cancer cells

Cited by 5 publications

References 39 publications

A comparative <i>in vitro</i> study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

A comparative <i>in vitro</i> study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

Aberrant stem cell and developmental programs in pediatric leukemia

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