Ablation of Red Stable Transfected Prostate Cancer Cell Lines by C-CPE Gold-Nanoparticle Mediated Laser Intervention

Author(s):  
Suhayla Alnajjar ◽  
Ingo Nolte ◽  
Annegret Becker ◽  
Tina Kostka ◽  
Jan Torben Schille ◽  
...  

Abstract Background: Claudin (CLDN) proteins have been described to be found and accordingly targeted to evaluate novel therapeutic approaches. C-terminus of Clostridium perfringens enterotoxin (C-CPE) binds efficiently several claudins and thus recombinant C-CPE conjugated to gold nanoparticles (AuNPs) has been used for cancer cell targeting using gold nanoparticle- mediated laser perforation (GNOME-LP). Cancer cells inoculation is routinely used to generate in vivo models to evaluate novel therapeutic approaches in prostate cancer. However, detailed characterization of cancer spreading and early tumor development and therapeutic response is often limited as conventional cell lines do not allow advanced deep tissue imaging.Methods: two canine prostate cancer cell lines were stably transfected with red fluorescent protein (RFP), followed by G418 selection. RFP marker as well as CLDN3, -4 and -7 expression was comparatively confirmed by flow cytometry, qPCR and immunofluorescences. For cancer cells targeting, GNOME-LP at a laser fluence of 72 mJ/cm² and a scanning speed of 0.5 cm/s was used. Statistical analysis was performed using SAS software 7.1, Dunnett´s Multiple Comparison Test and Student´s two-sided t-test. Differences were considered statistically significant for p<0.05.Results: we established two canine prostate carcinoma cell lines, stably expressing RFP allowing perspective deep tissue imaging. Directed C-CPE-AuNP binding to native and RFP transfected cells verified the capability to specifically target CLDN receptors. Cancer cell ablation was demonstrated in vitro setting using a combination of gold nanoparticle mediated laser perforation and C-CPE-AuNPs treatment reducing tumor cell viability to less than 10 % depending on cell line. Conclusion: the results confirm that this therapeutic approach can be used efficiently to target prostate carcinoma cells carrying a marker protein allowing deep tissue imaging. The established cell lines and the verified proof of concept in vitro study provide the basis for perspective Xenograft model in vivo studies. The introduce red fluorescence enables deep tissue imaging in living animals and therefore detailed characterization of tumor growth and subsequently possible tumor ablation through C-CPE-AuNPs treatment.

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 474 ◽  
Author(s):  
Muhammad Altaf ◽  
Naike Casagrande ◽  
Elena Mariotto ◽  
Nadeem Baig ◽  
Abdel-Nasser Kawde ◽  
...  

We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (C1–C8) and tested them in a panel of human cancer cell lines. We used osteosarcoma (MG-63), lung (A549), prostate (PC3 and DU145), breast (MCF-7), ovarian (A2780 and A2780cis, cisplatin- and doxorubicin-resistant), and cervical (ME-180 and R-ME-180, cisplatin resistant) cancer cell lines. We found that C2, C3, C6, and C7 were more cytotoxic than cisplatin in all cell lines tested and overcame cisplatin and doxorubicin resistance in A2780cis and R-ME-180 cells. In the PC3 prostate cancer cell line, the gold (III) complex C6 ([Au2(BPM)(DMDTC)2]Cl4) induced apoptosis and double-stranded DNA breaks, modified cell cycle phases, increased Reactive Oxigen Species (ROS) generation, and reduced thioredoxin reductase and proteasome activities. It inhibited PC3 cell migration and was more cytotoxic against PC3 cells than normal human adipose-derived stromal cells. In mice bearing PC3 tumor xenografts, C6 reduced tumor growth by more than 70% without causing weight loss. Altogether, our results demonstrate the anticancer activity of these new gold (III) complexes and support the potential of C6 as a new agent for prostate cancer treatment.


2010 ◽  
Vol 183 (4S) ◽  
Author(s):  
Chang-Deng Hu ◽  
Bennett Elzey ◽  
Jean Poulson ◽  
Wallace Morrison ◽  
Xuehong Deng ◽  
...  

Planta Medica ◽  
2020 ◽  
Vol 86 (18) ◽  
pp. 1401-1410
Author(s):  
Qi Zeng ◽  
Yun Zeng ◽  
Yonghua Zhan ◽  
Xu Nie ◽  
Yingying Guo

AbstractBritanin, a natural pseudoguaiacane sesquiterpene lactone, has significant antioxidant and anti-inflammatory activity, but little is known about its tumor inhibitory activity and the underlying mechanism. Here, we demonstrated in vitro and in vivo that britanin inhibited the growth of human prostate cancer cell lines (PC-3, PC-3-LUC, and DU-145). Through in vitro study, the results showed that britanin significantly decreased cell proliferation, migration, and motility. The moderate toxicity of britanin was determined with an acute toxicity study. A luciferase-labeled animal tumor xenograft model and bioluminescence imaging were applied, combining with biological validation for assessing the tumor progression. In vivo results demonstrated that britanin inhibited the growth of PC-3-LUC. The interleukin-2 level in mice was upregulated by britanin, which indicated that britanin induced antitumor immune activation. In addition, britanin downregulated the expression of nuclear factor (NF)-κB p105/p50, pp65, IκBα, pIκBα, phosphoinositide 3-kinase, pPI3k, Akt (protein kinase B, PKB), and pAkt proteins and upregulated expression of Bax. We discovered that britanin inhibits the growth of prostate cancer cells both in vitro and in vivo by regulating PI3K/Akt/NF-κB-related proteins and activating immunity. These findings shed light on the development of britanin as a promising agent for prostate cancer therapy.


Urology ◽  
2005 ◽  
Vol 66 (6) ◽  
pp. 1239-1244 ◽  
Author(s):  
Katsumi Shigemura ◽  
Toshiro Shirakawa ◽  
Yoshitaka Wada ◽  
Sadao Kamidono ◽  
Masato Fujisawa ◽  
...  

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 236-236
Author(s):  
Ferenc Rick ◽  
Andrew Abi-Chaker ◽  
Luca Szalontay ◽  
Norman L. Block ◽  
Gabor Halmos ◽  
...  

236 Background: Management of castration-resistant prostate cancer (CRPC) is challenging because of limitations in efficacy of current therapies. Somatostatin receptors are expressed in human CRPC. Here we tested targeted somatostatin AN-162 analog consisting of doxorubicin (DOX) conjugated to octapeptide RC-121, acting as a carrier, in human androgen-independent prostate cancer cell lines in vitro and in vivo. Methods: Expression of mRNA for the five subtypes of the somatostatin receptor in PC-3 and DU-145 human prostate cancer cell lines was evaluated by RT-PCR. Somatostatin receptor binding was measured with radioligand assays. The effect of AN-162 and DOX on the viability of PC-3 and DU-145 cells was assessed by MTS assay. Nude mice bearing PC-3 and DU-145 tumors were randomized to 5 groups (control, AN-162, DOX, somatostatin analog RC-160 as a control, and DOX + RC-160). Treatment consisted i.v. injections of AN-162, DOX, RC-160, DOX + RC-160, or vehicle once a week for 4 weeks. Tumor volume was measured every week; the study lasted 28 days. The doses of AN-162 were equivalent to 1.45 mg/kg DOX (2.5 μmol/kg). Results: The PC-3 and DU-145 cell lines were positive for the five subtypes of the somatostatin receptor. AN-162 and DOX (0.10–10 µM) inhibited the proliferation of PC-3 and DU-145 prostate cancer cells in a dose-dependent manner. AN-162 exerted a stronger inhibition of proliferation than DOX alone, but in vitro the difference was not significant. In vivo, AN-162 significantly inhibited growth of both tumor models’ compared with the controls and the groups given equimolar doses of doxorubicin, RC-160, or doxorubicin unconjugated to RC-160. Conclusions: Our work demonstrates potent inhibitory effects of AN-162 on somatostatin receptor positive androgen-independent prostate cancers, which were greater than any of the components of AN-162. The mechanisms of action of targeted cytotoxic analog of somatostatin AN-162 in CRPC should be explored. Our findings suggest the possible use of AN-162 in patients with CRPC.


1990 ◽  
Vol 143 (2) ◽  
pp. 381-385 ◽  
Author(s):  
Harold N. Keer ◽  
James M. Kozlowski ◽  
Yvonne C. Tsai ◽  
Chung Lee ◽  
Robert N. McEwan ◽  
...  

2021 ◽  
Author(s):  
Adriana Albini ◽  
Marco M. G. Festa ◽  
Nadja Ring ◽  
Denisa Baci ◽  
Michael Rehman ◽  
...  

Background. Cardiovascular toxicities still remain one of the most undesirable side effects in cancer patients receiving chemotherapy, and cardiotoxicity has been detected associated with many therapeutic regimens. A number of mechanisms are reported for these effects, some of which are related to inflammation, oxygen radical generation, mitochondrial damage. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, antioxidant activities which could exert protective effects on the heart cells. One very interesting derivative of EVOO preparation is represented by purified extract form waste waters. Here, we investigated the anti-cancer activity when combined with chemotherapeutics as well as potential cardioprotective activities of a polyphenol-rich extract from waste product of the EVOO, named A009. Methods and Results. Mice bearing prostate cancer (PCa) xenografts were treated with cisplatin with and without A009. Tumor cell growth was reduced by cis and by A009 and further hindered by the combination. The effects of the A009 extract on cardiovascular toxicities was investigated in vivo. The hearts of mice were analyzed, and the mitochondria were studied by transmission electron microscopy. A protection activity by A009 was observed. To confirm the in vivo data obtained with cisplatin therapy, tumor cell lines and rat cardiomyocytes were treated with cisplatin in vitro with and without A009. A009 enhanced cisplatin and 5FU reduced cancer cell growth while did not further affect co-treated rat cardiomyocytes. Another frequently used chemotherapeutic agent 5-fluorouracil (5FU), was also tested in this assay similar effects were observed. The cardioprotective effects of the A009 extract towards 5 FU chemotherapy were further investigated in a second system of in vitro cultures, on cardiomyocytes freshly isolated from mice pups. These cells were treated with 5-fluorouracil and A009. Wastewater extract mitigated the toxicity of the fluoropyrimidine. Conclusions. In vivo, we found synergisms of A009 and cisplatin in prostate cancer treatment. Hearts of mice xenografted with PCa cell lines and receiving co-treatment of A009 extracts along with cisplatin had reduced mitochondria damage compared to chemotherapy alone, indicating a cardioprotective role. A009 in vitro was additive to cisplatin and 5FU to reduce cancer cell growth while did not further affect rat cardiomyocytes cell cultures treated with cisplatin and 5FU. The A009 extract also rescued the proliferation rate of neonatal murine cardiomyocytes treated with 5-Fluorouracil. Our study demonstrates that the polyphenol-rich purified A009 extracts enhances the effect of chemotherapy in vitro and in vivo but mitigates effects on heart and heart cells. It could therefore represent a potential candidate for cardiovascular prevention in patients undergoing cancer chemotherapy.


2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3268
Author(s):  
Katja S. Håheim ◽  
Emil Lindbäck ◽  
Kah Ni Tan ◽  
Marte Albrigtsen ◽  
Ida T. Urdal Helgeland ◽  
...  

A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC50 = 24 nM) than Puromycin (IC50 = 270 nM) and Doxorubicin (IC50 = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).


Sign in / Sign up

Export Citation Format

Share Document