The simultaneous inhibition of the mTOR and MAPK pathways with Gnetin-C induces apoptosis in acute myeloid leukemia

Espinoza, J. Luis; El-Badry, Mahmoud; Taniwaki, Masafumi; Harada, Kenichi; Trung, Ly Quoc; Nakagawa, Noboru; Takami, Akiyoshi; Ishiyama, Ken; Yamauchi, Takuji; Takenaka, Katsuto; Nakao, Shinji

doi:10.1016/j.canlet.2017.04.027

Cited by 28 publications

(31 citation statements)

References 34 publications

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“…As mentioned above, only a few resveratrol oligomers have been investigated in animal studies, and only the oligomers derived from MSE have been tested in pharmacokinetic studies in humans. Gnetin C, a major constituent of MSE, is a well‐characterized resveratrol dimer with very promising antitumor potential, as demonstrated in mouse models of highly aggressive leukemia, although its efficacy in humans has yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the antileukemia effects of gnetin‐C, which were also confirmed in a mouse model harboring human AML cells, are mediated via the simultaneous inhibition of the ERK1/2 and AKT/mTOR pathways (Fig. ), two signals that are critical for the survival and growth of AML …”

Section: Gnetin‐cmentioning

confidence: 99%

“…On the basis of the above‐mentioned data, although no studies have been conducted to test the effects of pure gnetin‐C, gnetin‐C is expected to be safe for humans. The strongly synergistic effect between gnetin‐C and low doses of chemotherapeutic drugs, such as l ‐asparaginase, Ara‐C, and hydroxyurea, in killing leukemia cells suggests that this compound has considerable therapeutic potential and is likely a good candidate for neoadjuvant or adjuvant treatment or as part of a chemotherapeutic regimen to be tested in clinical trials.…”

Section: Gnetin‐cmentioning

confidence: 99%

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Gnetin‐C and other resveratrol oligomers with cancer chemopreventive potential

Espinoza

Inaoka

2017

Annals of the New York Academy of Sciences

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Resveratrol has been extensively studied to investigate its biological effects, including its chemopreventive potential against cancer. Over the past decade, various resveratrol oligomers, both naturally occurring and synthetic, have been described. These resveratrol oligomers result from the polymerization of two or more resveratrol units to form dimers, trimers, tetramers, or even more complex derivatives. Some oligomers appear to have antitumor activities that are similar or superior to monomeric resveratrol. In this review, we discuss resveratrol oligomers with anticancer potential, with emphasis on well-characterized compounds, such as the dimer gnetin-C and other oligomers from Gnetum gnemon, whose safety, pharmacokinetic, and biological activities have been studied in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Gnetin‐cmentioning

confidence: 99%

Section: Gnetin‐cmentioning

confidence: 99%

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Gnetin‐C and other resveratrol oligomers with cancer chemopreventive potential

Espinoza

Inaoka

2017

Annals of the New York Academy of Sciences

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“…The mAbs used for this study are listed in supplemental Table 7. The engraftment of human cells was assessed by PCR for the a-satellite region of human chromosome 17 as described previously 16 or by detecting human CD45 and HLA genes using genomic DNA from the BM and spleens of transplanted mice as templates. PCR was carried out with HotstarTaq Plus Master Mix (QIAGEN, Venlo, The Netherlands) using the primer sets listed in supplemental Table 6.…”

Section: Transplantation Of Human Icd34mentioning

confidence: 99%

“…In some experiments, adult mice (4-5 months of age) were used instead of young mice (5-6 weeks of age). The animals were maintained as described previously 16 and were euthanized at 9, 10, or 12 weeks after transplantation. The peripheral blood (PB), BM, spleens, and thymus were obtained and prepared for FCM and immunohistochemical analyses.…”

Section: Transplantation Of Human Icd34mentioning

confidence: 99%

Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack

et al. 2018

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Molecular Efficacy of Gnetin C as Dual‐Targeted Therapy for Castrate‐Resistant Prostate Cancer

Campanelli,

Deabel,

Puaar

et al. 2023

Molecular Nutrition Food Res

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ScopeResistance of castrate‐resistant prostate cancer (CRPC) to enzalutamide (Enz) involves the expression of constitutively active androgen receptor splice variant (AR‐V7). In addition to altered AR pathways, CRPC is characterized by “non‐AR‐driven” signaling, which includes an overexpression of metastasis‐associated protein 1 (MTA1). Combining natural compounds with anticancer drugs may enhance drug effectiveness while reducing adverse effects. In this study, the in vitro and in vivo anticancer effects of Gnetin C (GnC) alone and in combination with Enz against CRPC are examined.Methods and resultsThe effects of GnC alone and in combination with Enz are assessed by cell viability, clonogenic survival, cell migration, and AR and MTA1 expression using 22Rv1 cells. The tumor growth in vivo is assessed by bioluminescent imaging, western blots, RT‐PCR, and IHC. GnC alone and in combined treatment inhibit cell viability, clonogenic survival and migration, and AR and MTA1 expression in 22Rv1 cells. The underlying AR‐ and MTA1‐targeted anticancer mechanisms of treatments in vivo involve inhibition of proliferation and angiogenesis, and induction of apoptosis.ConclusionThe findings demonstrate that GnC alone and GnC combined with Enz effectively inhibits AR‐ and MTA1‐promoted tumor‐progression in advanced CRPC, which indicates its potential as a novel therapeutic approach for CRPC.

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The simultaneous inhibition of the mTOR and MAPK pathways with Gnetin-C induces apoptosis in acute myeloid leukemia

Cited by 28 publications

References 34 publications

Gnetin‐C and other resveratrol oligomers with cancer chemopreventive potential

Gnetin‐C and other resveratrol oligomers with cancer chemopreventive potential

Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack

Molecular Efficacy of Gnetin C as Dual‐Targeted Therapy for Castrate‐Resistant Prostate Cancer

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