Modulation of VP-16 cytotoxicity by carboplatin and 41.8°C hyperthermia

Katschinski, Dörthe M.; Jacobson, Elaine L.; Wiedemann, G. J.; Robins, H. Ian

doi:10.1007/s004320000223

Cited by 21 publications

(18 citation statements)

References 15 publications

(21 reference statements)

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“…2). The proton-proton correlations observed in the 1 3.15), together with 1 H-13 C long-range couplings in HMBC spectrum from 2-H, 12-H and 15,17-H to C-13 (d C 136.6) and 14,18-H to C-12 (d C 37.7) established a phenethyl residue. The protons of two singlet methyl groups 32-H (d H 1.42) and 33-H (d H 1.25) were each long-range coupled to an ester carbonyl carbon C-10 (d C 171.6), a quaternary carbon C-11 (d C 54.0) and a ketone carbonyl carbon C-1 (d C 203.7), which in turn were coupled to 2-H.…”

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confidence: 87%

Novel GRP78 Molecular Chaperone Expression Down-regulators JBIR-04 and -05 Isolated from Streptomyces violaceoniger

et al. 2007

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In the course of our screening program for regulators of the expression of GRP78 molecular chaperone, JBIR-04 (1) and -05 (2) were isolated from Streptomyces violaceoniger 4541-SVS3 as congeners of prunustatin A (3). The structures of 1 and 2 were determined by the analyses of the spectroscopic data. These compounds mainly consist of an amino acid and amino acid derived a -hydroxy acid residues. 1 and 2 inhibited the expression of GRP78 induced by 2-deoxyglucose in human fibrosarcoma HT1080 cells, but their activities were highly reduced compared with those of 3 and SW-163A.

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confidence: 87%

Novel GRP78 Molecular Chaperone Expression Down-regulators JBIR-04 and -05 Isolated from Streptomyces violaceoniger

et al. 2007

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“…GRP78 is a molecular chaperone in the endoplasmic reticulum (ER) induced by ER stress that promotes protein folding and plays an important role as a survival factor in solid tumors by providing resistance to both chemotherapy and hypoglycemic stress [1]. Therefore, specific downregulators of GRP78 transcription can reasonably be expected to become promising drugs in cancer chemotherapy.…”

Section: Abstract Streptomyces Versipellis Versipelostatin Moleculamentioning

confidence: 99%

A Novel Versipelostatin Analogue, Versipelostatin F Isolated from Streptomyces versipellis 4083-SVS6

et al. 2008

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A novel versipelostatin (1) analogue, versipelostatin F (2) was isolated from Streptomyces versipellis 4083-SVS6. The structure of 2 was determined by the analyses of the spectroscopic data. Compound 2 inhibited the expression of GRP78 induced by 2-deoxyglucose with an IC 50 value of 0.3 mM, which is 10-times more potent compared with that of 1. Keywords Streptomyces versipellis, versipelostatin, molecular chaperone, GRP78GRP78 is a molecular chaperone in the endoplasmic reticulum (ER) induced by ER stress that promotes protein folding and plays an important role as a survival factor in solid tumors by providing resistance to both chemotherapy and hypoglycemic stress [1]. Therefore, specific downregulators of GRP78 transcription can reasonably be expected to become promising drugs in cancer chemotherapy. In the course of our screening program for down-regulators of GRP78 molecular chaperone expression, we have isolated versipelostatin (1) Compound 1 is the first compound which has been found to down-regulate GRP78 expression induced by ER stress. Although the biological activities of 1, namely its inhibitory effects against GRP78 expression, were investigated in detail [9], its target is still unknown. Further investigation for congeners of 1 resulted in the isolation of a novel derivative, versipelostatin F (2), which showed stronger inhibitory activity against GRP78 expression than that of 1. In this paper, we report herein the isolation, structure elucidation and its brief biological activity of 2.The versipelostatin-producing strain, S. versipellis 4083-SVS6 was cultured at 27°C for 5 days in 50-liter jar fermentors containing 30 liters of a medium consisting of 2.5% starch, 1.5% soy bean meal, 0.2% dry yeast and 0.4% CaCO 3 (pH 6.2 before sterilization). The fermentation broth (60 liters) was centrifuged and the supernatant was extracted with EtOAc. The organic layer was dried over Na 2 SO 4 , and concentrated in vacuo. The dried residue was subjected to normal-phase MPLC (Purif-Pack SI-60, Moritex) by stepwise elution with a CHCl 3 -MeOH (5.0%, 10%, 20% MeOH, successively) solvent system. The 10% MeOH eluate (210 mg) was separated by reversed-phase MPLC (Purif-Pack ODS-100, Moritex) with a H 2 O -MeOH linear gradient system and further purified by preparative reversed-phase HPLC using a XBridge Prep C18 column (5.0 mm OBD, 19 i.d.ϫ150 mm, Waters) with 60% aqueous MeOH containing 0.4% diethylamine (flow rate, 10 ml/minute) to yield versipelostatin F (2, 31 mg; Rt, 23.2 minutes). The structure of 2 (Fig. 1) was mainly elucidated by NMR spectral analysis as follows.The physico-chemical properties of 2 are summarized in Table 1. Compound 2 was obtained as a colorless amorphous solid and its molecular formula was determined

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“…GRP78, which is well-known as a molecular chaperone in the endoplasmic reticulum (ER), also plays an important role as a survival factor in solid tumors, due to its acquisition of a resistant mechanism against both chemotherapy and hypoglycemic stress [1]. Thus, specific down-regulators of GRP78 transcription can reasonably be expected to become promising drugs in cancer chemotherapy [2].…”

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confidence: 99%

A Novel Antimycin-like Compound, JBIR-06, from Streptomyces sp. ML55

et al. 2008

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A novel compound of antimycin family, JBIR-06 (1), was isolated from Streptomyces sp. ML55. The structure of 1 was established as a twelve-membered macrocyclic skeleton with a 3-(formylamino)-2-hydroxybenzamide based on the spectroscopic data. Compound 1 inhibited the expression of GRP78 induced by 2-deoxyglucose at the IC 50 value of 250 nM.Keywords antimycin, JBIR-06, molecular chaperone, GRP78, Streptomyces sp. GRP78, which is well-known as a molecular chaperone in the endoplasmic reticulum (ER), also plays an important role as a survival factor in solid tumors, due to its acquisition of a resistant mechanism against both chemotherapy and hypoglycemic stress [1]. Thus, specific down-regulators of GRP78 transcription can reasonably be expected to become promising drugs in cancer chemotherapy [2]. In the course of our screening program for down-regulators of GRP78/Bip molecular chaperone expression, we isolated versipelostatin [3], prunustatin A [4, 5], JBIR-04, -05 [6] and SW-163A [6]. Further screening resulted in the isolation of a novel inhibitor of GRP78 expression, designated as JBIR-06 (1, Fig. 1), a new member of antimycin [7] family from mycelium of Streptomyces sp. ML55 [8]. In this paper, we report the isolation, structure elucidation, and brief biological activities of 1.The Streptomyces sp. ML55 was cultured at 27°C for 5 days in 500-ml Erlenmeyer flasks containing a medium consisting of 2.0% glycerin (Nacalai Tesque), 1.0% molasses (Dai-Nippon Meiji Sugar), 0.5% casein (KANTO CHEMICAL), 0.1% polypepton (NIHON PHARMACEUTICAL), 0.4% CaCO 3 (KOZAKAI PHARMACEUTICAL) (pH 7.2 before sterilization). The mycelium from the culture broth (2.0 liters) was extracted with Me 2 CO (400 ml). After concentrated in vacuo, the residue was extracted with EtOAc for two times. The organic layer was dried over Na 2 SO 4 , and concentrated in vacuo. The dried residue was applied to normal-phase MPLC (Purif-Pack SI-60, Moritex) and developed with a

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Modulation of VP-16 cytotoxicity by carboplatin and 41.8°C hyperthermia

Abstract: These data taken collectively, demonstrate a sequence effect (regarding the aforementioned antineoplastic agents), and provide a framework for future studies directed at the therapeutic optimization of the sequential application of carboplatin, hyperthermia, and VP-16.

Cited by 21 publications

References 15 publications

Novel GRP78 Molecular Chaperone Expression Down-regulators JBIR-04 and -05 Isolated from Streptomyces violaceoniger

Novel GRP78 Molecular Chaperone Expression Down-regulators JBIR-04 and -05 Isolated from Streptomyces violaceoniger

A Novel Versipelostatin Analogue, Versipelostatin F Isolated from Streptomyces versipellis 4083-SVS6

A Novel Antimycin-like Compound, JBIR-06, from Streptomyces sp. ML55

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