Resveratrol triggers anti-proliferative and apoptotic effects in FLT3-ITD-positive acute myeloid leukemia cells via inhibiting ceramide catabolism enzymes

Ersöz, Nur Şebnem; Adan, Aysun

doi:10.1007/s12032-021-01627-2

Cited by 10 publications

(8 citation statements)

References 37 publications

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“…(122). Moreover, resveratrol also triggers anti-proliferative and apoptotic effects in FLT3-ITDpositive acute myeloid leukemia cells through inhibition of ceramide catabolic enzymes (119,134). Vincristine is a vinca alkaloid that can be obtained from the Madagascar periwinkle Catharanthus roseus (135,136).…”

Section: Natural Products For Sphingolipidbased Anticancer Therapeuticsmentioning

confidence: 99%

“…Resveratrol, extracted from Polygonum cuspidatum Sieb.et Zucc ., induces autophagy in gastric cancer cells (HGC-27) by inhibiting dihydroceramide desaturase and increasing dihydroceramide ( 122 ). Moreover, resveratrol also triggers anti-proliferative and apoptotic effects in FLT3-ITD-positive acute myeloid leukemia cells through inhibition of ceramide catabolic enzymes ( 119 , 134 ). Vincristine is a vinca alkaloid that can be obtained from the Madagascar periwinkle Catharanthus roseus ( 135 , 136 ).…”

Section: Natural Products For Sphingolipid-based Anticancer Therapeuticsmentioning

confidence: 99%

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The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance

Wang

et al. 2022

Front. Oncol.

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Biologically active sphingolipids are closely related to the growth, differentiation, aging, and apoptosis of cancer cells. Some sphingolipids, such as ceramides, are favorable metabolites in the sphingolipid metabolic pathway, usually mediating antiproliferative responses, through inhibiting cancer cell growth and migration, as well as inducing autophagy and apoptosis. However, other sphingolipids, such as S1P, play the opposite role, which induces cancer cell transformation, migration and growth and promotes drug resistance. There are also other sphingolipids, as well as enzymes, played potentially critical roles in cancer physiology and therapeutics. This review aimed to explore the important roles of sphingolipid metabolism in cancer. In this article, we summarized the role and value of sphingolipid metabolism in cancer, including the distribution of sphingolipids, the functions, and their relevance to cancer diagnosis and prognosis. We also summarized the known and potential antitumor targets present in sphingolipid metabolism, analyzed the correlation between sphingolipid metabolism and tumor immunity, and summarize the antitumor effects of natural compounds based on sphingolipids. Through the analysis and summary of sphingolipid antitumor therapeutic targets and immune correlation, we aim to provide ideas for the development of new antitumor drugs, exploration of new therapeutic means for tumors, and study of immunotherapy resistance mechanisms.

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Section: Natural Products For Sphingolipidbased Anticancer Therapeuticsmentioning

confidence: 99%

Section: Natural Products For Sphingolipid-based Anticancer Therapeuticsmentioning

confidence: 99%

The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance

Wang

et al. 2022

Front. Oncol.

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“…248 Resveratrol, an anti-carcinogenic plant-derived polyphenol was shown to inhibit the proliferation of FLT3-ITD mutated MV4-11 and MOLM-13 cells via modulation of sphingolipid metabolism enzymes including anti-apoptotic sphingosine kinase-1 and glucosylceramide synthase and apoptotic serine palmitoyltransferase. 249,250 Although the studies investigating the roles of flavonoids in FLT3 positive AML are limited, natural products or their derivatives seem to possess the potential to develop new therapeutic agents targeting FLT3 or to be used as an integrative medicine in combination with FLT3i.…”

Section: Flavonoids In Flt3 Amlmentioning

confidence: 99%

Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches

Tecik¹,

Adan²

2022

OTT

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FMS-like tyrosine kinase 3 (FLT3) is mutated in approximately 30% of acute myeloid leukemia (AML) patients. The presence of FLT3-ITD (internal tandem duplication, 20–25%) mutation and, to a lesser extent, FLT3-TKD (tyrosine kinase domain, 5–10%) mutation is associated with poorer diagnosis and therapy response since the leukemic cells become hyperproliferative and resistant to apoptosis after continuous activation of FLT3 signaling. Targeting FLT3 has been the focus of many pre-clinical and clinical studies. Hence, many small-molecule FLT3 inhibitors (FLT3is) have been developed, some of which are approved such as midostaurin and gilteritinib to be used in different clinical settings, either in combination with chemotherapy or alone. However, many questions regarding the best treatment strategy remain to be answered. On the other hand, various FLT3-dependent and -independent resistance mechanisms could be evolved during FLT3i therapy which limit their clinical impact. Therefore, identifying molecular mechanisms of resistance and developing novel strategies to overcome this obstacle is a current interest in the field. In this review, recent studies of approved FLT3i and knowledge about major resistance mechanisms of clinically approved FLT3i’s will be discussed together with novel treatment approaches such as designing novel FLT3i and dual FLT3i and combination strategies including approved FLT3i plus small-molecule agents targeting altered molecules in the resistant cells to abrogate resistance. Moreover, how to choose an appropriate FLT3i for the patients will be summarized based on what is currently known from available clinical data. In addition, strategies beyond FLT3i’s including immunotherapeutics, small-molecule FLT3 degraders, and flavonoids will be summarized to highlight potential alternatives in FLT3-mutated AML therapy.

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“…Resveratrol was previously shown to cause apoptosis in HL-60 cells due to the accumulation of ceramides and a reduction in SPHK1 and GCS expression [ 178 ]. Building on this, a recent study assessed the independent and combinatorial effects of SKI-II (SPHK1 inhibitor) and PDMP (GCS inhibitor) with resveratrol in MOLM-13 and MV4-11 leukemic cells [ 179 ]. In line with previous observations, resveratrol decreased SPHK1 protein levels, as well as GCS.…”

Section: Sls In Hematological Malignanciesmentioning

confidence: 99%

“…In line with previous observations, resveratrol decreased SPHK1 protein levels, as well as GCS. Inhibition of these enzymes with SKI-II and PDMP led to an additional decrease in cell viability, as well as increased apoptosis as measured by PARP and caspase-3 cleavage [ 179 ]. One interesting conundrum is the effect of resveratrol on SPT and the role played by SPT in the response to resveratrol treatment.…”

Section: Sls In Hematological Malignanciesmentioning

confidence: 99%

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

Raza

Atallah²,

Luberto³

2022

IJMS

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Dysregulation of sphingolipid metabolism plays a complex role in hematological malignancies, beginning with the first historical link between sphingolipids and apoptosis discovered in HL-60 leukemic cells. Numerous manuscripts have reviewed the field including the early discoveries that jumpstarted the studies. Many studies discussed here support a role for sphingolipids, such as ceramide, in combinatorial therapeutic regimens to enhance anti-leukemic effects and reduce resistance to standard therapies. Additionally, inhibitors of specific nodes of the sphingolipid pathway, such as sphingosine kinase inhibitors, significantly reduce leukemic cell survival in various types of leukemias. Acid ceramidase inhibitors have also shown promising results in acute myeloid leukemia. As the field moves rapidly, here we aim to expand the body of literature discussed in previously published reviews by focusing on advances reported in the latter part of the last decade.

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Resveratrol triggers anti-proliferative and apoptotic effects in FLT3-ITD-positive acute myeloid leukemia cells via inhibiting ceramide catabolism enzymes

Cited by 10 publications

References 37 publications

The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance

The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance

Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

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