Phthoxazolin A inhibits prostate cancer growth by modulating tumor–stromal cell interactions

Kawada, Manabu; Inoue, Hiroyuki; Usami, Ihomi; Ikeda, Daishiro

doi:10.1111/j.1349-7006.2008.00996.x

Cited by 31 publications

(33 citation statements)

References 33 publications

(46 reference statements)

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“…These genetically altered fibroblasts also produce elevated TGF- β [49]. In retrospect, it becomes apparent that these CAF cells not only produced an increased level of TGF- β , but also produced an increased level of IGF-I [50, 51]. We hypothesize that under the combined influence of elevated TGF- β and IGF-I, along with the input from androgen/estrogen signaling, the adjacent epithelial cells eventually developed into prostate cancer.…”

Section: Role Of the Adjacent Stroma In Prostate Carcinogenesismentioning

confidence: 99%

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Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-βand IGF Signaling

Lee

Jia

Rahmatpanah

et al. 2014

BioMed Research International

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This review postulates the role of transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between TGF-β and IGF signaling occupies a central part in this stromal-epithelial interaction. An increase in TGF-β and IGF signaling will set off the imbalance of this relationship and will lead to cancer development. A continuous input from TGF-β and IGF in the tumor microenvironment will result in cancer progression. Understanding of these events can help prevention, diagnosis, and therapy of prostate cancer.

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Section: Role Of the Adjacent Stroma In Prostate Carcinogenesismentioning

confidence: 99%

“…Prostate CAF cells are able to produce IGF-I in response to TGF- β [50, 51]. Likewise, CAF cells are able to produce TGF- β 1 in response to IGF-I [53].…”

Section: Role Of the Adjacent Stroma In Prostate Carcinogenesismentioning

confidence: 99%

Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-βand IGF Signaling

Lee

Jia

Rahmatpanah

et al. 2014

BioMed Research International

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“…Although the study of the precise mechanism is going on, 1 and 2 are considered to modulate the tumor-stromal cell interactions similar to other compounds reported previously. [6][7][8] As we obtained a new compound with potency of antitumor effect in vivo, we thought that our screening concept and program would be beneficial for the innovation of new antitumor drugs. …”

Section: Discussionmentioning

confidence: 99%

“…3,5 Using the assay method as a screening system for antitumor compounds, we have been finding several compounds that exert antitumor effects through modulation of the tumor-stromal cell interactions. 6,7 We have recently reported that leucinostatin A, a fungus natural compound, showed antitumor effect against xenograft models of human prostate cancer cells in vivo through the downregulation of insulin-like growth factor-I secretion from PrSCs. 8 By continuing the screening system, we have found new natural compounds from a fungal strain Perisporiopsis melioloides Mer-f16716.…”

Section: Introductionmentioning

confidence: 99%

NBRI16716A, a new antitumor compound against human prostate cancer cells, produced by Perisporiopsis melioloides Mer-f16716

et al. 2010

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Prostate stroma can regulate the growth and metastasis of prostate cancer through the tumor-stromal cell interactions. Thus, small molecules that modulate the tumor-stromal cell interactions will have a chance to become new antitumor drugs. In the course of our screening of the modulators, we isolated three new natural compounds, NBRI16716A (1), NBRI16716B (2) and NBRI16716C (3), from the fermentation broth of Perisporiopsis melioloides Mer-f16716, although compound 2 was already reported as a chemical degradation product of isotriornicin. Compounds 1 and 2 inhibited the growth of human prostate cancer DU-145 cells in the coculture with human prostate stromal cells (PrSCs) more strongly than that of DU-145 cells alone. Furthermore, both compounds showed antitumor effect against xenograft models of DU-145 cells and PrSCs in vivo.

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“…Natural products were used as the major source for our screening platform; the structural variety of natural products is expected to bait a diverse array of counterpart proteins. In fact, several natural products exhibit the desired activity and selectivity, including phthoxazolin A, 10) NBRI23477 A and B, 11) leucinostatins, 12) and intervenolin. 13,14) Two of NBRI16716s 15) (Fig.…”

mentioning

confidence: 99%

Synthesis and Structure–Activity Relationship Study of NBRI16716B, an Antitumor Natural Product

Abe

Sakashita

Kawada

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The total synthesis of NBRI16716B (2), a naturally occurring modulator of tumor-stroma interactions, was successfully achieved. Using this synthetic route, a dehydroxy analogue (21) and a derivative lacking the 5-hydroxy-3-methylpentenoyl side chain (22) became accessible. A preliminary structure-activity relationship study to unveil the structural requirements for selective inhibition of tumor cells cocultured with stromal cells revealed that both of the hydroxamate structures of 2 are indispensable, whereas the 5-hydroxy-3-methylpentenoyl side chain is not essential.

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Phthoxazolin A inhibits prostate cancer growth by modulating tumor–stromal cell interactions

Cited by 31 publications

References 33 publications

Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-βand IGF Signaling

Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-βand IGF Signaling

NBRI16716A, a new antitumor compound against human prostate cancer cells, produced by Perisporiopsis melioloides Mer-f16716

Synthesis and Structure–Activity Relationship Study of NBRI16716B, an Antitumor Natural Product

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