Therapeutic strategy using phenotypic modulation of cancer cells by differentiation‐inducing agents

Honma, Yoshio; Akimoto, Masumi

doi:10.1111/j.1349-7006.2007.00575.x

Cited by 15 publications

(13 citation statements)

References 46 publications

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“…Combined treatment with IFNα and cotylenin A preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells and significantly inhibited the growth of human lung cancer cells as xenografts without apparent adverse effects, suggesting that this combination may have therapeutic value in treating human cancer (5)(6)(7). These findings suggest that cotylenin A may be useful in the therapy for leukemia and some other malignancies.…”

Section: Introductionmentioning

confidence: 82%

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Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models

Takahashi

Honma

Miyake

et al. 2015

International Journal of Oncology

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Abstract. Multiple myeloma is a malignant proliferative disease of plasma cells in the bone marrow and remains largely incurable. Cotylenin A, a fusicoccane diterpene glycoside with a complex sugar moiety, was isolated as a plant-growth regulator. Cotylenin A has been shown to inhibit the growth of various cancer cells. Herein, we examined the anti-myeloma effects of cotylenin A using five human myeloma cell lines (RPMI-8226, KMS-11, KMS-26, KMS-12 PE and KMS-12 BM) and xenografts in immunodeficient mice. Cotylenin A and vincristine synergistically inhibited the growth and induced apoptosis in myeloma cells. While other microtubule-disturbing agents also showed co-operative effects with cotylenin A, other anticancer agents, such as doxorubicin, cisplatin, camptothecin, methotrexate, gemcitabine and 5-fluorouracil, did not show such co-operation with cotylenin A. These differences might be attributed to the effects on autophagic responses. Combined treatment with cotylenin A and vincristine induced autophagy (formation of LC3-II and degradation of p62 protein). However, doxorubicin did not enhance the autophagy induced by cotylenin A. A colony-forming assay indicated that the combined treatment with cotylenin A and vincristine more effectively suppressed the formation of large colonies, which have higher self-renewal activity than vincristine alone. Expression of pluripotency-associated transcription factor Sox2 mRNA in RPMI-8226 myeloma cells was significantly suppressed by treatment with cotylenin A. Combined treatment with cotylenin A and vincristine significantly inhibited the growth of KMS-26 myeloma cells as xenografts. Our results suggest that the combination of cotylenin A and vincristine may have therapeutic value. Recently, it was reported that cotylenin A modulates the 14-3-3 intracellular signaling pathway. The 14-3-3 proteins may be novel targets in treating myeloma.However, our study could not explain how the sensitization to vincristine is related to the effects of cotylenin A on the 14-3-3 signaling pathway and further studies will be needed.

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Section: Introductionmentioning

confidence: 82%

“…The upper side of the polycarbonate filter of the Transwell chamber was coated with matrigel. Cells (2x10 5 ) were suspended in 800 µl of serum-free medium that contained 1 mg/ml bovine serum albumin to maintain the osmotic pressure, and placed in the upper chamber. The lower chamber was filled with 10% serum-medium (1000 µl).…”

Section: Methodsmentioning

confidence: 99%

Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models

Takahashi

Honma

Miyake

et al. 2015

International Journal of Oncology

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“…Conversely, overexpression of MKP-1 decreases Microphthalmia degradation via ERK dephosphorylation and facilitates melanocyte differentiation (Wellbrock et al, 2002). The finding that MKP-1 overexpression can, under certain circumstances, induce cells to differentiate could be interesting if proven true for tumors, as one of the therapeutic axes for the control of tumors relies on inducing them to differentiate to the cell lineage from which they originate, whether the tumors are of hematological origin (Tsiftsoglou et al, 2003) or solid tumors (Honma and Akimoto, 2007).…”

Section: (Z)-1-[n-(2-aminoethyl)-n-(2-ammonioethyl) Amino]diazen-1-mentioning

confidence: 99%

Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer

Boutros

Chevet²,

Metrakos³

2008

Pharmacol Rev

504

448

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“…1A) and some diterpene glucosides produced by plant-pathogenic fungi are modulators of 14-3-3 proteins, and have been shown to induce the differentiation of human myeloid leukemia cells and apoptosis in human carcinoma cells in the presence of interferon-α [6][7][8] . 1A) and some diterpene glucosides produced by plant-pathogenic fungi are modulators of 14-3-3 proteins, and have been shown to induce the differentiation of human myeloid leukemia cells and apoptosis in human carcinoma cells in the presence of interferon-α [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

“…Cotylenin A also affected the differentiation of leukemic cells that were freshly isolated from acute myeloid leukemia patients in primary culture [6]. Combined treatment with interferon-α and cotylenin A significantly inhibited the growth of human lung cancer cells as xenografts without apparent adverse effects [7,8]. Administration of cotylenin A significantly prolonged the survival of mice that had been inoculated with retinoid-sensitive and -resistant NB4 cells with no appreciable adverse effects [9].…”

Section: Introductionmentioning

confidence: 99%

A Novel Fusicoccin Derivative Preferentially Targets Hypoxic Tumor Cells and Inhibits Tumor Growth in Xenografts

Kawakami¹,

Hattori²,

Inoue³

et al. 2012

ACAMC

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Malignant cells in solid tumors survive under prolonged hypoxia and can be a source of resistance to current cancer therapies. Tumor hypoxia is also associated with a more malignant phenotype and poor survival in cancer patients. Recent progress in our understanding of the biology of tumor cells under hypoxia has led to increased attention on targeting hypoxia for cancer therapy. We report here that a novel fusicoccin derivative (ISIR-042), but not its parent or related compounds such as fusicoccin A and cotylenin A, is more cytotoxic to hypoxic cells than to normoxic cells. The hypoxia-induced accumulation of hypoxia-inducible factor (HIF)-1α and the phosphorylation of Akt were effectively inhibited by treatment with ISIR-042, suggesting that the preferential cytotoxicity toward hypoxic cells is associated with a reduction of HIF-1α and Akt activation. ISIR-042 inhibited the growth of human pancreatic cancer MIAPaCa-2 cells while sparing normal endothelial cells, and significantly inhibited the growth of MIAPaCa-2 cells as xenografts without apparent adverse effects. Pancreatic cancer cells expressing CD24 and CD44 exhibited characteristics of stem cells. Treatment with gemcitabine increased this stem cell-enriched population, and this effect was significantly inhibited by ISIR-042, suggesting that ISIR- 042 preferentially inhibits stem/progenitors in pancreatic cancer cell lines compared with chemotherapeutic agents. These results suggest that ISIR-042 may be a potential therapeutic agent for hypoxic tumors such as pancreatic cancer.

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Therapeutic strategy using phenotypic modulation of cancer cells by differentiation‐inducing agents

Cited by 15 publications

References 46 publications

Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models

Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models

Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer

A Novel Fusicoccin Derivative Preferentially Targets Hypoxic Tumor Cells and Inhibits Tumor Growth in Xenografts

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