Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells

Hiss, Donavon C; Gabriels, Gary; Folb, Peter I.

doi:10.1186/1475-2867-7-5

Cited by 48 publications

(42 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BI is a much simpler and straightforward way of measuring interactions than Loewe additivity, which requires examination of interactions across a gradient of concentrations for each of the drugs. Although Loewe integrates more information about interactions, the ease of measurement and calculation of BI has led to its use in a huge number of studies [8,14,21,29,[45][46][47][48][49], including our present one.…”

Section: Discussionmentioning

confidence: 99%

Enhanced identification of synergistic and antagonistic emergent interactions among three or more drugs

Tekin

Beppler

White

et al. 2016

J. R. Soc. Interface.

100

View full text Add to dashboard Cite

Interactions among drugs play a critical role in the killing efficacy of multidrug treatments. Recent advances in theory and experiment for three-drug interactions enable the search for emergent interactions-ones not predictable from pairwise interactions. Previous work has shown it is easier to detect synergies and antagonisms among pairwise interactions when a rescaling method is applied to the interaction metric. However, no study has carefully examined whether new types of normalization might be needed for emergence. Here, we propose several rescaling methods for enhancing the classification of the higher order drug interactions based on our conceptual framework. To choose the rescaling that best separates synergism, antagonism and additivity, we conducted bacterial growth experiments in the presence of single, pairwise and triple-drug combinations among 14 antibiotics. We found one of our rescaling methods is far better at distinguishing synergistic and antagonistic emergent interactions than any of the other methods. Using our new method, we find around 50% of emergent interactions are additive, much less than previous reports of greater than 90% additivity. We conclude that higher order emergent interactions are much more common than previously believed, and we argue these findings for drugs suggest that appropriate rescaling is crucial to infer higher order interactions.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced identification of synergistic and antagonistic emergent interactions among three or more drugs

Tekin

Beppler

White

et al. 2016

J. R. Soc. Interface.

100

View full text Add to dashboard Cite

show abstract

“…TNM enhances the sensitivity of not only drug-resistant NIH-3T3-MDR cells but also drugsensitive NIH-3T3 cells to P-gp substrates (such as DOX and VCR) or to cisPt, a P-gp-untransportable drug (Hiss et al 1996). These pharmacomodulatory effects of TNM are assumed to be mediated by global inhibition of protein and glycoprotein synthesis and synergistic interaction with antineoplastic drugs (Hiss et al 2007). Hiss et al (2007) also concluded that the ability of TNM to enhance the sensitivity of drug-resistant tumor cells may impact the design and optimization of novel resistance modifiers for combination treatment of intractable neoplasms.…”

Section: Discussionmentioning

confidence: 99%

“…These pharmacomodulatory effects of TNM are assumed to be mediated by global inhibition of protein and glycoprotein synthesis and synergistic interaction with antineoplastic drugs (Hiss et al 2007). Hiss et al (2007) also concluded that the ability of TNM to enhance the sensitivity of drug-resistant tumor cells may impact the design and optimization of novel resistance modifiers for combination treatment of intractable neoplasms. Application of TNM increases the cellular level of UDP-N-acetylglucosamine, which was associated with distention of the endoplasmic reticulum and the nuclear membranes (Morin and Bernacki 1983).…”

Section: Discussionmentioning

confidence: 99%

The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin

Pavlíková

Šereš²,

Imrichova³

et al. 2016

gpb

View full text Add to dashboard Cite

Abstract. In P-gp-positive cell variants obtained from L1210 cells either by selection with vincristine (L1210/R) or by transfection with the human gene encoding P-gp (L1210/T), we have previously described cross-resistance to tunicamycin (TNM), a protein N-glycosylation inhibitor. Here we studied whether this cross-resistance also underlies P-gp-positive variants of human acute myeloid leukemia cells (AML) derived from SKM-1 and MOLM-13 cells (SKM-1/VCR, SKM-1/LEN, MOLM-13/ VCR) by selection with vincristine (VCR) and lenalidomide (LEN). While SKM-1/LEN cells were P-gp positive, no P-gp was detected in MOLM-13/LEN cells. P-gp-positive cells could be repeatedly passaged in medium containing TNM. In contrast, more than 90% of P-gp-negative cells were entering and progressing through cell death mechanisms after the third passage in medium containing TNM. Combined apoptosis/necrosis cell death was detected in L1210 cells after exposure to TNM. Passaging of P-gp-negative AML cells in medium containing TNM induced preferentially apoptosis. Damage to P-gp-negative cells induced with TNM was associated with arrest in the G1 phase of the cell cycle. P-gp-positive leukemia cells differed from P-gp-negative cells in the composition of plasma membrane glycoproteins, which we monitored with the aid of different lectins. The application of TNM to cells induced additional changes in membrane-linked glycosides.

show abstract

“…Even if using the relatively sensitive drug, such as gemcitabine, doxorubicin, tunicamycin and ifosfamide, the clinical remission rate is only about 10%-20% (Hiss et al, 2007;Chumworathayi, 2013;Pitakkarnkul et al, 2013;Su et al, 2013). Because this group of patients have treated with multiple cycles of chemotherapy, causing hematological and non hematological toxicity accumulation, we chosed only single gemcitabine combined with 125 I-seed implantation treatment as the therapy for patients.…”

Section: Adverse Reactionsmentioning

confidence: 99%

Efficacy of Permanent Iodine-125 Seed Implants and Gemcitabine Chemotherapy in Patients with Platinum-Resistant Recurrent Ovarian Carcinoma

Yang

Liu²,

Xu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: The aim of this study was to explore the efficacy and adverse reactions of CT-guided radioactive 125I-seed implantation treatment combined with chemotherapy for platinum-resistant recurrent ovarian carcinoma. Materials and Methods: From September 2010 to December 2012, 23 patients with platinum-resistant recurrent ovarian carcinoma were enrolled. All the patients refused, could not bear, or were not suitable for surgery. They all had no more than 3 lesions, which were detected and could also be measured by CT. All were clarified as single-lesion or multiple-lesion groups. A total of 41 lesions underwent implantation of from 8 to 106 125I seeds (median=43). Multi-plane implanting was adopted and 125I-seeds of (0.4-0.7)mCi were placed at intervals of (0.5-1.0) cm. After implantation treatment, all patients underwent 4 cycles of chemotherapy with gemcitabine 800 mg/m2 (days 1, 8 and 15). Results: The outcome was evaluated with CT 3 weeks and every 3 months after implantation treatment. After 6 months, the volume of 32 out of 41 lesions (78.0%) was reduced at least 30%, within which 9 lesions completely disappeared(22.0%). Complete response was observed in 7 cases (30.4%), with a partial response in 4 cases (17.4%),4 cases stable(17.4%)and 8 cases showing progression (34.8%). The total clinical remission rate was 47.8% (11/23). The clinical remission rate was 77.8% (7/9) in the single-lesion group and 28.6% (4/14) in the multiple-lesion group with a significant difference between the two(P=0.036). The common side effects observed were mild gastrointestinal reactions. Conclusions: 125I-seed implantation combined with chemotherapy applies an effective way in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma with the advantages of high local control rates, good short-term effects, little trauma and less side effects.

show abstract

Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells

Cited by 48 publications

References 94 publications

Enhanced identification of synergistic and antagonistic emergent interactions among three or more drugs

Enhanced identification of synergistic and antagonistic emergent interactions among three or more drugs

The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin

Efficacy of Permanent Iodine-125 Seed Implants and Gemcitabine Chemotherapy in Patients with Platinum-Resistant Recurrent Ovarian Carcinoma

Contact Info

Product

Resources

About