Effects of differentiation-inducing factors of Dictyostelium discoideum on human leukemia K562 cells: DIF-3 is the most potent anti-leukemic agent

Kubohara, Yuzuru

doi:10.1016/s0014-2999(99)00548-8

Cited by 66 publications

(87 citation statements)

References 18 publications

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“…Indeed, upregulated Drp1 activity is essential for the induction of apoptosis by Benzil isothiocyanate (BITC), Differentiation -Inducing -Factor 3 (DIF-3), Micheliolide (MCL) and CGP37157 [154][155][156][157].…”

Section: Mitochondrial Dynamics As Possible Therapeutic Targetsmentioning

confidence: 99%

The mitochondrial dynamics in cancer and immune-surveillance

Simula

Nazio

Campello

2017

Seminars in Cancer Biology

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A B S T R A C TMitochondria-shaping proteins control the dynamic equilibrium between fusion and fission of the mitochondrial network. Their balance is strictly required to regulate various processes, including the quality of mitochondria, cell metabolism, cell death, proliferation and cell migration. Alterations in these processes are frequently encountered in cancer, during both its onset and later progression, as evidence emerge connecting alterations in mitochondrial dynamics with cancer development. In recent years, novel therapeutic approaches to fight against different human tumors aim at exploiting the immune system's ability to specifically recognize tumor antigens, thus killing malignant cells in a process named immune-surveillance. Interestingly, data are accumulating on the role that mitochondrial dynamics play also for the correct function of both the innate and the adaptive immune system. By this review, we overview how mitochondrial dynamics can affect various processes during cancer development, acting directly on tumor cells or indirectly on cells responsible for tumor aggression and defence.

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Section: Mitochondrial Dynamics As Possible Therapeutic Targetsmentioning

confidence: 99%

The mitochondrial dynamics in cancer and immune-surveillance

Simula

Nazio

Campello

2017

Seminars in Cancer Biology

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“…In the DIF family (DIF-1, DIF-2, and DIF-3), DIF-3 is the most potent inhibitor of proliferation in mammalian cells (81). However, the target molecule of DIFs is unknown, even in Dictyostelium.…”

Section: -4 Potential Drug Targetsmentioning

confidence: 99%

The Wnt/β-Catenin Signaling Pathway as a Target in Drug Discovery

2007

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Abstract. The cell signaling cascades provoked by Wnt proteins (the Wnt signaling pathways), which are well conserved through evolution, play crucial roles to maintain homeostasis of a variety of tissues such as skin, blood, intestine, and brain, as well as to regulate proliferation, morphology, motility, and fate of cells during embryonic development. Among these pathways, the signal transduction through β-catenin (the Wnt / β-catenin signaling pathway) has been most intensively studied because this signal regulates the expression of a number of genes essential for cell proliferation and differentiation and also this pathway is perturbed in a number of diseases such as cancers, bone diseases, and cardiovascular diseases. However, there is no therapeutic agents that can selectively modulate the Wnt / β-catenin signaling pathway, although some existing drugs (e.g., non-steroidal anti-inflammatory drugs, vitamins, and imatinib mesylate) have been suggested to inhibit this pathway. Here we provide an overview of the Wnt / β-catenin signaling pathway: its roles in physiology and pathology and the possibility as a target in development of new drugs.

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“…To date, we and others have shown that DIF-1, DIF-3, and their derivatives suppress cell growth and occasionally induce or promote cell differentiation in both cancer cells and non-transformed (normal) mammalian cells. [6][7][8][9][10][11][12][13][14][15] In addition, some DIF derivatives promote glucose consumption in mammalian cells in vitro and in vivo [16][17][18] ; others regulate interleukin 2 (IL-2) production in human Jurkat T cells [19][20][21] and suppress innate immune responses in Drosophila S2 cells. 21) Furthermore, some derivatives of DIF-3, specifically 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)-heptan-1-one (DIF-3(+2)) and 1-(3-chloro-2,6-dihydroxy-4-ethoxyphenyl)hexan-1-one (Bu-DIF-3) (Fig.…”

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Biological Activities of Novel Derivatives of Differentiation-Inducing Factor 3 from <i>Dictyostelium discoideum</i>

Takahashi

Kikuchi

Nguyen

et al. 2017

Biological & Pharmaceutical Bulletin

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Differentiation-inducing factor-3 (DIF-3; 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one), which is found in the cellular slime mold Dictyostelium discoideum, is a potential candidate compound for the development of new medicines; DIF-3 and its derivatives possess several beneficial biological activities, including anti-tumor, anti-Trypanosoma cruzi, and immunoregulatory effects. To assess the relationship between the biological activities of DIF-3 and its chemical structure, particularly in regard to its alkoxy group and the length of the alkyl chains at the acyl group, we synthesized two derivatives of DIF-3, 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)octan-1-one (DIF-3(+3)) and 1-(3-chloro-2,6-dihydroxy-4-butoxyphenyl)-hexan-1-one (Hex-DIF-3), and investigated their biological activities in vitro. At micro-molar levels, DIF-3(+3) and Hex-DIF-3 exhibited strong anti-proliferative effects in tumor cell cultures, but their anti-T. cruzi activities at 1 µM in vitro were not as strong as those of other known DIF derivatives. In addition, Hex-DIF-3 at 5 µM significantly suppressed mitogen-induced interleukin-2 production in vitro in Jurkat T cells. These results suggest that DIF-3(+3) and Hex-DIF-3 are promising leads for the development of anti-cancer and immunosuppressive agents. Key words anti-tumor agent; Dictyostelium discoideum; interleukin-2; Jurkat cell; Trypanosoma cruziThe characteristic chlorinated alkylphenones differentiationinducing factor-1 (DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-one) and DIF-3 (1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-one) (Fig. 1A) were originally identified as stalk-cell differentiation-inducing factors in the cellular slime mold Dictyostelium discoideum, [1][2][3][4] an excellent model organism for studying cell and developmental biology. 5) Recently, cellular slime molds have attracted interest as potential novel drug resources. To date, we and others have shown that DIF-1, DIF-3, and their derivatives suppress cell growth and occasionally induce or promote cell differentiation in both cancer cells and non-transformed (normal) mammalian cells. [6][7][8][9][10][11][12][13][14][15] In addition, some DIF derivatives promote glucose consumption in mammalian cells in vitro and in vivo [16][17][18] ; others regulate interleukin 2 (IL-2) production in human Jurkat T cells [19][20][21] and suppress innate immune responses in Drosophila S2 cells. 21) Furthermore, some derivatives of DIF-3, specifically 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)-heptan-1-one (DIF-3(+2)) and 1-(3-chloro-2,6-dihydroxy-4-ethoxyphenyl)hexan-1-one (Bu-DIF-3) (Fig. 1A), have potent biological effects against tumors, Trypanosoma cruzi, and inflammation 9,12,15,19,20,22,23) ; the protozoan T. cruzi causes Chagas disease (American trypanosomiasis) in humans. The differing pharmacological activities of various DIF derivatives might reflect specific modifications of their side chains. Taken together, these findings highlight the potential of DIF derivatives in the treatment of ...

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Effects of differentiation-inducing factors of Dictyostelium discoideum on human leukemia K562 cells: DIF-3 is the most potent anti-leukemic agent

Cited by 66 publications

References 18 publications

The mitochondrial dynamics in cancer and immune-surveillance

The mitochondrial dynamics in cancer and immune-surveillance

The Wnt/β-Catenin Signaling Pathway as a Target in Drug Discovery

Biological Activities of Novel Derivatives of Differentiation-Inducing Factor 3 from <i>Dictyostelium discoideum</i>

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