Telomerase inhibitor MST-312 induces apoptosis of multiple myeloma cells and down-regulation of anti-apoptotic, proliferative and inflammatory genes

Ameri, Zahra; Ghiasi, Saeedeh; Farsinejad, Alireza; Hassanshahi, Gholamhossein; Ehsan, Mohsen; Fatemi, Ahmad

doi:10.1016/j.lfs.2019.04.060

Cited by 23 publications

(12 citation statements)

References 41 publications

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“…Aside from synthetic compound, various naturally occurring compounds, such as allicin (from garlic), curcumin (from turmeric), silibinin (from thistle), and epigallocathechin gallate (EGCG, from tea) were found to have telomerase inhibitory properties ( 202 ). A synthetic, more stable derivative of EGCG, MST-312, was shown to inhibit telomerase in various cancer, although its mechanism of action remains unknown ( 203 – 205 ).…”

Section: Tert As a Potential Therapeutic Targetmentioning

confidence: 99%

TERT—Regulation and Roles in Cancer Formation

et al. 2020

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Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase. Telomerase complex plays a key role in cancer formation by telomere dependent or independent mechanisms. Telomere maintenance mechanisms include complex TERT changes such as gene amplifications, TERT structural variants, TERT promoter germline and somatic mutations, TERT epigenetic changes, and alternative lengthening of telomere. All of them are cancer specific at tissue histotype and at single cell level. TERT expression is regulated in tumors via multiple genetic and epigenetic alterations which affect telomerase activity. Telomerase activity via TERT expression has an impact on telomere length and can be a useful marker in diagnosis and prognosis of various cancers and a new therapy approach. In this review we want to highlight the main roles of TERT in different mechanisms of cancer development and regulation.

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Section: Tert As a Potential Therapeutic Targetmentioning

confidence: 99%

TERT—Regulation and Roles in Cancer Formation

et al. 2020

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“…MST‐312, major catechin of green tea, is a chemically modified analogue of green tea epigallocatechin gallate 135 . MST‐312 competitively binds to the active site of hTERT and possesses two different effects.…”

Section: Telomerase Targeting In Haematological Malignanciesmentioning

confidence: 99%

“…expression of regulated genes such as survivin, Bcl-2, Mcl-1, c-Myc and hTERT by inhibiting NF-κB activity 137. The treatment with MST-312 in pre-B ALL multiple myeloma cells promotes the suppression of cell growth and induction of apoptosis by up-regulation of Bax/Bcl-2 ratio, and down-regulation of c-Myc, hTERT, IL-6 and TNF-α genes 135,138. 6.4 | AzidothymidineNucleoside Analogs are the first compounds used for the treatment of viral infections.…”

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confidence: 99%

Telomerase‐based therapies in haematological malignancies

Rafat

Asl

Mazloumi

et al. 2022

Cell Biochemistry & Function

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Telomeres are specialized genetic structures present at the end of all eukaryotic linear chromosomes. They progressively get shortened after each cell division due to end replication problems. Telomere shortening (TS) and chromosomal instability cause apoptosis and massive cell death. Following oncogene activation and inactivation of tumour suppressor genes, cells acquire mechanisms such as telomerase expression and alternative lengthening of telomeres to maintain telomere length (TL) and prevent initiation of cellular senescence or apoptosis. Significant TS, telomerase activation and alteration in expression of telomere‐associated proteins are frequent features of different haematological malignancies that reflect on the progression, response to therapy and recurrence of these diseases. Telomerase is a ribonucleoprotein enzyme that has a pivotal role in maintaining the TL. However, telomerase activity in most somatic cells is insufficient to prevent TS. In 85‐90% of tumour cells, the critically short telomeric length is maintained by telomerase activation. Thus, overexpression of telomerase in most tumour cells is a potential target for cancer therapy. In this review, alteration of telomeres, telomerase and telomere‐associated proteins in different haematological malignancies and related telomerase‐based therapies are discussed.

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“…It also acts as a factor of growth and differentiation of B cells and stimulates their immunoglobulin production. IL-6 is involved in the pathogenesis of myeloma, and it is used as a prognostic factor for the disease (16,(20)(21)(22).…”

Section: Cytokine Profilesmentioning

confidence: 99%

Modern markers for evaluating bone disease in multiple myeloma (Review)

et al. 2021

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Multiple myeloma (MM) is a bone marrow neoplasia with increasing incidence compared to previous years. Although new therapeutic molecules have been introduced, it remains an incurable disease with severe repercussions to patients. For many patients, bone disease represents a severe problem often causing pain, pathological bone fractures, and spinal cord compression, which affects the quality of life. This article analyzes the main markers of bone destruction in MM as well as risk factors for severe bone damage. Bone complications have a negative impact on the quality of life of patients with MM, along with other associated complications (renal failure, hypogammaglobulinemia, osteolytic bone disease, hypercalcemia, anemia). The markers of bone destruction described in this article include: interleukin (IL)-6, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), amino-and carboxy-terminal cross-linking telopeptide of type I collagen (NTX, CTX), human bone sialoprotein (BSP) and dickkopf-1 secreted glycoprotein (DKK1). The future practical applicability of this literature review would be the large-scale determination of markers of bone destruction that correlate with the negative evolution to complications of bone disease or the implications that these markers have in regards to treatment.

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Telomerase inhibitor MST-312 induces apoptosis of multiple myeloma cells and down-regulation of anti-apoptotic, proliferative and inflammatory genes

Cited by 23 publications

References 41 publications

TERT—Regulation and Roles in Cancer Formation

TERT—Regulation and Roles in Cancer Formation

Telomerase‐based therapies in haematological malignancies

Modern markers for evaluating bone disease in multiple myeloma (Review)

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