Combined 3-O-acetylbetulin treatment and carbonic anhydrase IX inhibition results in additive effects on human breast cancer cells

Petrenko, Marina; Güttler, Antje; Funtan, Anne; Kessler, Jacqueline; Emmerich, Daniel J.; Paschke, Ralf; Vordermark, Dirk; Bache, Matthias

doi:10.1016/j.cbi.2020.109326

Cited by 17 publications

(6 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BA has clearly proven its effectiveness in vitro and in vivo in the treatment of many malignant neoplasms (i.e., melanoma, hepatocellular carcinoma, colorectal, lung, breast, prostate, stomach, pancreas, neck and head, ovary cancers, glioblastoma multiforme, and chronic myeloid leukemia). It has also shown selectivity, with no or very little effect on normal cells even at doses as high as 500 mg/kg body weight [ 46 , 47 , 48 ]. In addition, BA developed for topical application (20% betulinic acid ointment) was assessed in a phase I/II clinical trial for dysplastic lesions that may evolve into melanoma.…”

Section: Discussionmentioning

confidence: 99%

Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines

Wróblewska-Łuczka

Cabaj

Bąk

et al. 2022

IJMS

View full text Add to dashboard Cite

The incidence of melanoma is steadily increasing worldwide. Melanoma is the most lethal skin cancer, and new therapeutic methods are being sought. Our research aimed to investigate the cytotoxic and antiproliferative effects of betulinic acid in vitro, used alone and in combination with taxanes (paclitaxel, docetaxel) in four melanoma cell lines. Isobolographic analysis allowed us to assess the interactions between these compounds. Betulinic acid had no cytotoxic effect on normal human keratinocyte HaCaT cells; the amount of LDH released by them was significantly lower compared to melanoma cell lines. The present study shows that betulinic acid significantly inhibits the growth of melanoma cell lines in vitro. The IC50 values of betulinic acid ranged from 2.21 µM to 15.94 µM against the four melanoma lines. Co-treatment of betulinic acid with paclitaxel or docetaxel generated desirable drug–drug interactions, such as an additive and additive with a tendency to synergy interactions.

show abstract

Section: Discussionmentioning

confidence: 99%

Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines

Wróblewska-Łuczka

Cabaj

Bąk

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…These include the effects on prostate cancer cells of SLC-0111 alone or in combination with daunorubicin 242 , radiobiological effects of CA IX inhibition in human breast cancer cells 243 , microvascular endothelial cell pH regulation 244 , glycolysis and migration suppression in pulmonary microvascular endothelial cells 245,246 , involvement of CA isoforms in mitochondrial biogenesis and in the control of lactate production in human Sertoli cells 246 . Very recently, SLC-0111 was combined with 3-O-acetylbetulin for the treatment of CA IX-positive tumours by Vordermark's group, again with excellent synergistic effects 247 . Dedhar's group recently reported the interconnection between CA IX inhibition and the amino acid and acid/base transporters in hypoxic tumours 248 as well as the possibility to overcome the adaptive resistance to KRAS and MEK inhibitors by using such anticancer agents in combination with SLC-0111 249 .…”

Section: Discussionmentioning

confidence: 99%

Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase

Nocentini

Carta

Winum

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Inorganic anions inhibit the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) generally by coordinating to the active site metal ion. Cyanate was reported as a non-coordinating CA inhibitor but those erroneous results were subsequently corrected by another group. We review the anion CA inhibitors (CAIs) in the more general context of drug design studies and the discovery of a large number of inhibitor classes and inhibition mechanisms, including zinc binders (sulphonamides and isosteres, dithiocabamates and isosteres, thiols, selenols, benzoxaboroles, ninhydrins, etc.); inhibitors anchoring to the zinc-coordinated water molecule (phenols, polyamines, sulfocoumarins, thioxocoumarins, catechols); CAIs occluding the entrance to the active site (coumarins and derivatives, lacosamide), as well as compounds that bind outside the active site. All these new chemotypes integrated with a general procedure for obtaining isoform-selective compounds (the tail approach) has resulted, through the guidance of rigorous X-ray crystallography experiments, in the development of highly selective CAIs for all human CA isoforms with many pharmacological applications.

show abstract

“…As far as current medical knowledge goes, there is no single treatment capable of curing cancer. Recent studies have shown that multi-mode therapy is often more effective than singlemode therapy in inhibiting tumors (39)(40)(41). In our study, we investigated the combined treatment of immunogene therapy and magnetic fluid hyperthermia using Fe 3 O 4 nanoparticles as the medium on cancer, which demonstrated strong synergies.…”

Section: Discussionmentioning

confidence: 99%

The therapeutic effect of PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres combined with magnetic fluid hyperthermia on hepatoma

Zhang

Chen

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent and deadly malignant tumors with serious clinical and socioeconomic consequences. Although gene therapy holds great promise in the treatment of hepatoma, its clinical applications are hindered by uncontrolled gene transmission and transcription.MethodsThe pY-ads-8-5HRE-cfosp-IFNG plasmid was constructed and identified by double enzyme digestion and gene sequencing. The expression of pYr-ads-8-5HRE-cfosp-IFNG in HepG2 cells was detected by quantitative PCR. PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres were prepared and characterized. In vitro heating test of magnetic albumin nanospheres in an alternating magnetic field (AMF) was carried out. The therapeutic effect of PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres on hepatocellular carcinoma was investigated by cell and animal experiments. After treatment, mice blood was collected for clinical biochemical analysis and histopathological evaluation of major organs was performed to assess potential adverse effects of treatment.ResultsDouble enzyme digestion and gene sequencing showed that the pY-ads-8-5HRE-cfosp-IFNG plasmid was constructed successfully. QPCR results showed that the IFNγ transcript level in the PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG group was higher than that in the PEI-Fe3O4/pYr-ads-8-cfosp-IFNG group after being treated with hypoxia (P<0.05). TEM revealed that the self-prepared PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres exhibit an approximately spherical or elliptical shape. The hydrodynamic size of the albumin nanospheres was 139.7 nm. The maximum temperature of 0.25 mg/mL solution is stable at about 44°C, which is suitable for tumor thermal therapy without damaging normal tissues. The relative cell inhibition rate of the radiation-gene therapy and MFH combination group was higher than that of other control groups in CCK8 experiment. (P<0.05) Flow cytometry showed that the apoptosis rate and necrosis rate of the combined treatment group were 42.32% and 35.73%, respectively, higher than those of the other groups. (P<0.05) In animal experiments, the mass and volume inhibition rates of the combined treatment group were 66.67% and 72.53%, respectively, higher than those of other control groups. (P<0.05) Clinical biochemical analysis and histopathological evaluation showed no abnormality.ConclusionsThe results indicated the successful construction of the radiation-induced plasmid and demonstrated that the hypoxia enhancer could augment the expression of INFγ in a hypoxia environment. Gene therapy combined with magnetic fluid hyperthermia (MFH) has exhibited excellent outcomes in both cell and animal studies. Our experiments demonstrated that the PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres system is a comprehensive treatment method for hepatoma, which can effectively combine immune genre therapy with hyperthermia.

show abstract

Combined 3-O-acetylbetulin treatment and carbonic anhydrase IX inhibition results in additive effects on human breast cancer cells

Cited by 17 publications

References 56 publications

Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines

Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines

Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase

The therapeutic effect of PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres combined with magnetic fluid hyperthermia on hepatoma

Contact Info

Product

Resources

About