Insulin and novel thioglycosides exert suppressive effect on human breast and colon carcinoma cells

Agrawal, Siddarth; Woźniak, Marta; Łuc, Mateusz; Walaszek, K; Pielka, Ewa; Szeja, W.; Pastuch-Gawołek, Gabriela; Gamian, Andrzej; Ziółkowski, Piotr

doi:10.18632/oncotarget.23170

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…We and others have designed new syntheses for pyridine thioglycosides, which have shown strong cytotoxicity against various human cancer cell lines and block proliferation of various cancer cell lines (Komor et al, 2012;Elgemeie et al, 2015). It has also been shown that thioglycosides involving pyridine and dihydropyridine groups exert inhibitory effects on both DNA-containing viruses and inhibitors of protein glycosylation (Agrawal et al, 2017;Elgemeie et al, 2010;Masoud et al, 2017). Based on these significant biological findings and with the aim of identifying new potent chemotherapeutics as new anticancer agents with improved pharmacological and safety profiles, we have prepared several new non-classical thioglycosides containing the pyridine ring.…”

Section: Chemical Contextmentioning

confidence: 99%

Crystal structure of racemic 2-[(β-arabinopyranosyl)sulfanyl]-4,6-diphenylpyridine-3-carbonitrile

Hammad

Masoud

Elgemeie

et al. 2018

Acta Crystallogr E Cryst Commun

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In the racemic title compound, the sulfur atom is attached equatorially to the sugar ring with unequal S—C bonds. The dihedral angles between the pyridine ring and its attached phenyl groups are 42.24 (8) and 6.37 (14)°. In the crystal, a system of classical O—H⋯O and O—H⋯(O,O) hydrogen bonds links the molecules to form tube-like assemblies propagating parallel to the c-axis direction.

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Section: Chemical Contextmentioning

confidence: 99%

Crystal structure of racemic 2-[(β-arabinopyranosyl)sulfanyl]-4,6-diphenylpyridine-3-carbonitrile

Hammad

Masoud

Elgemeie

et al. 2018

Acta Crystallogr E Cryst Commun

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“…The elevated glucose intake requires the overexpression of glucose transporters (GLUTs), which is frequent in neo-plasms and provide clinical targets for therapy [ 7 , 8 ]. Therefore, glycoconjugation, in which cytotoxic agents or targeted anticancer therapeutics have been linked to glucose, can improve the selective uptake of anticancer drugs [ 9 , 10 , 11 , 12 , 13 , 14 ]. Since the introduction of glufosfamide [ 15 ], the potential of this strategy in diagnosis and therapy has already been realized, yet there is tremendous scope for improvement [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Efficacy of a Novel Glucose–Methotrexate Conjugate in Targeted Cancer Treatment

Woźniak

Pastuch-Gawołek

Makuch

et al. 2021

IJMS

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Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose–methotrexate conjugate (GLU–MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter−1 (GLUT1). GLU–MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU–MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-α-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU–MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU–MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.

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“…Besides, insulin enhances cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells [ 17 ]. Insulin enhances the effects of chemotherapeutic agents on colorectal cancer while single using not showing toxicity [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Insulin reverses choriocarcinoma 5- fluorouracil resistance

Shan

Han

et al. 2021

Bioengineered

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Choriocarcinoma (CC) is a gestational trophoblastic tumor secondary to a gravid or non-gravid pregnancy. It is characterized by rapid growth, high invasion, and high metastatic potential and chemotherapy resistance that significantly affect survival rate of CC patients. Insulin is implicated in alleviation of chemotherapy resistance in CC. However, the mechanism of reversing resistance in CC has not been explored. Our purpose was to explore insulin effect on 5-fluorouracil (5-FU) resistance in CC and elucidate its potential mechanism in vitro and in vivo. CKK-8, colony formation, Transwell, and flow cytometry were used to detect the effect of insulin on 5-FU resistance in CC cells JEG-3 and JARS. Xenograft mice were used to evaluate the effect of insulin on 5-FU resistance. Results showed that insulin combined with 5-FU suppressed cell viability by 30% in JEG-3 and 43% in JAR compared with 5-FU alone in 72 h. What's more, insulin combined with 5-FU promoted cell apoptosis, inhibited cell proliferation, migration, and phosphorylation of survivin at residue threonine 34 (Thr34) and drug resistance-related proteins, P-GP and MRP1 levels (p < 0.05). In vivo experiment showed Insulin combined with 5-FU suppressed tumor volume by 35% compared with 5-FU alone and 73% compared with control in CC xenograft mice. In summary, the findings of this study show that insulin reversed chemoresistance of CC cells to 5-FU by inhibiting phosphorylation of survivin. Development of a therapeutic strategy that combines insulin with the chemotherapeutic agent 5-FU has a great potential in improving survival of CC patients.

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Insulin and novel thioglycosides exert suppressive effect on human breast and colon carcinoma cells

Cited by 6 publications

References 35 publications

Crystal structure of racemic 2-[(β-arabinopyranosyl)sulfanyl]-4,6-diphenylpyridine-3-carbonitrile

Crystal structure of racemic 2-[(β-arabinopyranosyl)sulfanyl]-4,6-diphenylpyridine-3-carbonitrile

In Vitro and In Vivo Efficacy of a Novel Glucose–Methotrexate Conjugate in Targeted Cancer Treatment

Insulin reverses choriocarcinoma 5- fluorouracil resistance

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