scholarly journals Anti-cancer potential of cannabis terpenes in a taxol-resistant model of breast cancer

2021 ◽  
Author(s):  
Andre M Tomko ◽  
Erin G Whynot ◽  
Lauren F O'Leary ◽  
Denis J Dupre
Keyword(s):  
Breast Cancer ◽  
Therapeutic Potential ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Effects ◽  
Cellular Invasion ◽  
Breast Cancer Outcomes ◽  
Anti Cancer ◽  
Resistant Breast Cancer Cell ◽  
Apoptotic Cascade

Chemotherapeutic resistance can limit breast cancer outcomes; therefore, the exploration of novel therapeutic options is warranted. Isolated compounds found in cannabis have previously been shown to exhibit anti-cancer effects, but little is known about their effects in resistant breast cancer. Our study aims to evaluate the effects of terpenes found in cannabis in in vitro chemotherapy-resistant model of breast cancer. We aimed to identify whether five terpenes found in cannabis produced anti-cancer effects, and if their effects were improved upon co-treatment with cannabinoids and flavonoids also found in cannabis. Nerolidol and β-caryophyllene produced the greatest cytotoxic effects, activated the apoptotic cascade and reduced cellular invasion. Combinations with the flavonoid kaempferol potentiated the cytotoxic effects of ocimene, terpinolene, and β-myrcene. Combinations of nerolidol and δ9-tetrahydrocannabinol or cannabidiol produced variable responses ranging from antagonism and additivity to synergy, depending on concentrations used. Our results indicate that cannabis terpenes, alone or combined with cannabinoids and flavonoids, produced anti-cancer effects in chemotherapy-resistant breast cancer cell lines. This study is a first step in the identification of compounds that could have therapeutic potential in the treatment of resistant breast cancer.

Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents

2019 ◽  
Vol 19 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Faeze Khalili ◽  
Sara Akrami ◽  
Malihe Safavi ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Mina Saeedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
High Yield ◽  
Breast Cancer Cell Lines ◽  
Pyridine Derivatives ◽  
One Pot ◽  
Standard Drug ◽  
Three Component Reaction ◽  
Anti Cancer

Background: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives. Objective: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated. Methods: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death. Results: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods. Conclusion: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.

scholarly journals Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+ Metastasic Breast Cancer

Nanomaterials ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1793 ◽  
Author(s):  
Enrique Niza ◽  
María del Mar Noblejas-López ◽  
Iván Bravo ◽  
Cristina Nieto-Jiménez ◽  
José Antonio Castro-Osma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Breast Cancer Cell Lines ◽  
Her2 Positive ◽  
Multikinase Inhibitor ◽  
Biodegradable Nanoparticles

Dasatinib (DAS) is a multikinase inhibitor that acts on several signaling kinases. DAS is used as a second-line treatment for chronic accelerated myeloid and Philadelphia chromosome-positive acute lymphoblastic leukemia. The therapeutic potential of DAS in other solid tumours is under evaluation. As for many other compounds, an improvement in their pharmacokinetic and delivery properties would potential augment the efficacy. Antibody-targeted biodegradable nanoparticles can be useful in targeted cancer therapy. DAS has shown activity in human epidermal growth factor receptor 2 (HER2) positive tumors, so conjugation of this compound with the anti-HER2 antibody trastuzumab (TAB) with the use of nanocarriers could improve its efficacy. TAB-targeted DAS-loaded nanoparticles were generated by nanotechnology. The guided nanocarriers enhanced in vitro cytotoxicity of DAS against HER2 human breast cancer cell lines. Cellular mechanistic, release studies and nanoparticles stability were undertaken to provide evidences for positioning DAS-loaded TAB-targeted nanoparticles as a potential strategy for further development in HER2-overexpressing breast cancer therapy.

Synthesis and Evaluation of 198Au/PAMAM-MPEG-FA against Cancer Cells

2020 ◽  
Vol 20 (10) ◽  
pp. 1250-1265
Author(s):  
Reza Rezaei ◽  
Simin Janitabar Darzi ◽  
Mahnaz Yazdani
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Therapeutic Potential ◽  
Analytical Techniques ◽  
Cell Uptake ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Clinical Investigations ◽  
Anti Cancer

Background: There is a significant dearth of clinical biochemistry researches to evaluate the facility of exploitation of folate targeted radioactive gold-labeled anti-cancer drugs against various cancer cell lines. Objective: The aim of this paper was to develop a gold-based compound with an efficient therapeutic potential against breast cancer. To this end, the synthesis of the 198Au/PAMAM-MPEG-FA composite was considered here. Methods: The radioactive gold (198Au) nanoparticles were encapsulated into Folic acid (FA)-targeted Polyamidoamine dendrimer (PAMAM) modified with Maleimide-Polyethylene glycol Succinimidyl Carboxymethyl ester (MPEG). After that, anticancer assessments of the prepared 198Au/PAMAM-MPEG-FA hybrid mater against breast cancer were investigated. : Further studies were also devised to compare the anticancer capabilities of the 198Au/PAMAM-MPEG-FA composite with the synthesized P-MPEG, 197Au/P-MPEG, 197Au/P-MPEG-FA, 197Au/P-FA and 198Au/P-MPEG-FA conjugates. The prepared drugs were characterized by means of various analytical techniques. The radionuclidic purity of the 198Au/P-MPEG-FA solution was determined using High Purity Germanium (HPGe) spectroscopy and its stability in the presence of human serum was studied. The cell uptake and toxicity of the prepared drugs were evaluated in vitro, and some comparative studies of the toxicity of the drugs were conducted towards the MCF7 (Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell). Results: The results showed that cell uptake of 198Au/P-MPEG-FA nanoparticles is high in the 4T1 cell line and the order of uptake is as 4T1> MCF7> C2C12. Moreover, of the tested compounds, 198Au/P-MPEG-FA had the highest toxicity towards the cancerous 4T1 and MCF7 in all concentrations after 24, 48 and 72h (P < 0.001). Furthermore, the cytotoxicity of the drugs was concentration-dependent. Conclusion: On the basis of the present research, 198Au/P-MPEG-FA has been proposed as a good candidate for the induction of cell death in breast cancer, although further experimental and clinical investigations are required.

scholarly journals Characterization of SN38-Resistant T47D Breast Cancer Cell Sublines Overexpressing BCRP, MRP1, MRP2, MRP3, and MRP4

2021 ◽  
Author(s):  
Hee-Jeong Lee ◽  
Cheol-Hee Choi
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Drug Accumulation ◽  
Breast Cancer Cell Lines ◽  
Wild Type ◽  
T47d Breast Cancer Cell ◽  
Anti Cancer ◽  
Resistant Breast Cancer Cell

Abstract BackgroundAlthough several novel resistant breast cancer cell lines have been established, only a few resistant breast cancer cell lines overexpress breast cancer resistance proteins (BCRP). The aim of this study was to establish new resistant breast cancer cell lines overexpressing BCRP using SN38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of irinotecan and was to discover genes and mechanisms associated with multidrug resistance.MethodsSN38-resistant T47D breast cancer cell sublines were selected from the wild-type T47D cells by gradually increasing SN38 concentration. The sensitivity of the cells to anti-cancer drugs was assessed by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Expression profiles of the resistance-related transporters were examined using the resistance diagnostic kit (Drugsporter®), real time RT-PCR, and western blot analysis. Intracellular drug accumulation in the resistant cells was determined using flow cytometry.ResultsThe SN38-resistant T47D breast cancer cell sublines T47D/SN120 and T47D/SN150 were established after long-term exposure (more than 16 months) of wild-type T47D cells to 120 nM and 150 nM SN38, respectively. T47D/SN120 and T47D/SN150 cells were more resistant to SN38 (14.5 and 59.1 times, respectively), irinotecan (1.5 and 3.7 times, respectively), and topotecan (4.9 and 12 times, respectively), than the wild-type parental cells. Both T47D/SN120 and T47D/SN150 sublines were cross-resistant to various anti-cancer drugs. These resistant sublines overexpressed mRNAs of MRP1, MRP2, MRP3, MRP4, and BCRP. The DNA methylase inhibitor 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor trichostatin A increased the expression levels of BCRP, MRP1, MRP2, MRP3, and MRP4 transcripts in T47D/WT cells. Drug accumulation was found to be lower in T47D/SN120 and T47D/SN150 cells, compared to that in T47D/WT cells. However, treatment with known chemosensitizers increased the intracellular drug accumulation and sensitivity of anti-tumor agents.ConclusionT47D/SN120 and T47D/SN150 cells overexpressed MRP1, MRP2, MRP3, MRP4, and BCRP due to the suppression of epigenetic gene silencing via DNA hypermethylation and histone deacetylation. Although these resistant cells present a higher resistance to various anti-cancer drugs than their parental wild-type cells, multidrug resistance was overcome by treatment with chemosensitizers. These SN38 resistant T47D breast cancer cell sublines expressing resistance proteins can be useful for the development of new chemosensitizers.

scholarly journals A Unique 3D In Vitro Cellular Invasion Assay

2012 ◽  
Vol 17 (8) ◽  
pp. 1088-1095 ◽  
Author(s):  
Daniela F. Quail ◽  
Tamara J. Maciel ◽  
Kem Rogers ◽  
Lynne M. Postovit
Keyword(s):  
Breast Cancer ◽  
Cell Culture ◽  
Cancer Cell ◽  
3D Cell Culture ◽  
Breast Cancer Cell Lines ◽  
Invasion Assay ◽  
Cell Culture Techniques ◽  
Culture Techniques ◽  
Cellular Invasion

Three-dimensional (3D) cell culture techniques using a bioreactor have been used to co-culture various breast cancer cell lines. Comparisons between 3D co-cultures containing different proportions of breast cancer cell lines have been made with respect to cluster size, cell surface marker distribution, and Ki67 expression. Furthermore, an observed difference in invasion through collagen between co-cultures has been briefly reported. However, these assays have not yet been developed into a quantifiable methodology to assess the effects of drugs and/or microenvironments on cellular invasion. From a cancer perspective, two important aspects of cellular invasion that are often left out of in vitro assays are considerations about the 3D structural heterogeneity of the primary tumor and the ability of cells to migrate in all directions. Accordingly, we have taken advantage of the methodology previously described for 3D cell culture techniques and have developed a 3D invasion assay using cell clusters that can be used to assess the effects of different drugs and treatment conditions on cancer cell invasion. We also describe a novel whole-mount technique that permits fluorescence-based immunolocalization of proteins through the entire tumorsphere, without the need for sectioning. Our assay provides a simple, inexpensive, and physiologically relevant context to study cellular invasion in vitro, in a way that recapitulates an in vivo milieu.

Screening of Amodiaquine for its in vitro Anti-cancer Activity on Breast Cancer Cell Lines- a Case Study for Drug Reprofiling

2021 ◽  
Vol 5 (2) ◽  
pp. 263-273
Author(s):  
Kehinde S. Salako
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Flow Cytometry Analysis ◽  
Anti Cancer ◽  
Cancer Activity

Background: Cancer is one of the foremost contributors to global disease bur den and constantly requires new therapeutic options. The development of new drugs has failed to keep up with its incidence. Hence, drug reprofiling strategies are emerging as novel therapeutic options. The study aimed to evaluate the anti-cancer activity of amodiaquine (anti-malarial drug) using a combination of murine and human breast cancer cell lines Methods: Amodiaquine was authenticated by ultra-violet spectrophotometry, high- performance liquid chromatography and 1D nuclear magnetic resonance. In vitro cytotoxicity of amodiaquine was evaluated against three breast cancer cell lines. MDA-MB-453, 4T1 and MDA-MB-231 cells were incubated with the drug at different concentrations (0.78, 1.56, 3.13, 6.25, 12.50, 25.00, 50.00, 100.00 μM) for 72 h, after which cell viability testing was conducted using the cell counting kit-8 assay. Negative control in which no drug was added to the cells was also evaluated. The flow cytometry analysis of MDA-MB-231 cells when treated with amodiaquine was also evaluated by a flow cytometer using annexin V/propidium iodide staining assay. Results: Cell viability studies showed that the IC50 values of amodiaquine on MDA-MB-453, 4T1, and MDAMB-231 cells were 6.48 ± 1.12, 10.50 ± 1.17, and 19.23 ± 1.16 μM, respectively. The flow cytometry analysis of MDA-MB-231 cancer cells treated with amodiaquine showed cancer cell death by necrosis. Conclusion: This study has shown that amodiaquine may be potentially reprofiled as an anti-cancer agent in managing androgen receptor-positive / HER-2 positive and triple-negative breast cancer types. An additional probable mechanism of action of anti-cancer activity of amodiaquine was found to be necrosis .

scholarly journals Synthesis and Anti-Cancer Activity Evaluation of Novel 1,3,4-Oxadiazole Substituted 5-Arylidene/Isatinylidene-2-Iminothiazolidin-4-Ones

2021 ◽  
Vol 12 (1) ◽  
pp. 1161-1173
Keyword(s):  
Breast Cancer ◽  
1H Nmr Spectroscopy ◽  
Knoevenagel Condensation ◽  
Ammonium Thiocyanate ◽  
Aromatic Aldehydes ◽  
Breast Cancer Cell Lines ◽  
Anti Cancer ◽  
Isatin Derivatives ◽  
Cancer Activity

Following the interaction of 2-chloro-N-(5-aryl-1,3,4-oxadiazole-2-yl) acetamides 1a-b with ammonium thiocyanate in dry acetone, the 5-unsubstituted 2-imino-4-thiazolidinones 4a-b have been synthesized. Compounds 4a-b were subsequently utilized in Knoevenagel condensation with aromatic aldehydes or isatin derivatives to synthesize the series of 5-arylidene/isatinylidene substituted 2-(1,3,4-oxadiazol-2-yl)imino-4-thiazolidinones 5a-h and 6a-d. The structures of target compounds were confirmed by using 1H NMR spectroscopy and elemental analysis. Evaluation of anti-cancer activity in vitro for the synthesized compounds was performed following the National Cancer Institute protocol against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines. As a result, the most active compound 5a, namely 2-[5-(4-chlorophenyl)-[1,3,4]oxadiazol-2-ylimino]-5-(4-methoxybenzylidene)thiazolidin-4-one was found to be a highly efficient anti-tumor candidate with average logGI50 and logTGI values of -5.19 and -4.09, respectively.

scholarly journals Chitosan-Modified Silver Nanoparticles Enhance Cisplatin Activity in Breast Cancer Cells

2020 ◽  
Vol 11 (3) ◽  
pp. 10572-10584
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Cancer Drug ◽  
Breast Cancer Cell Lines ◽  
Anti Cancer ◽  
Silver Nps ◽  
Sensitivity Specificity

Cancer therapy has been hindered by treatments lacking sensitivity, specificity, and affordability. The side effects of conventional chemotherapy enforce the need for a treatment strategy that would maximize the anti-cancer activity of the drug while minimizing its’ adverse effects on healthy cells. Nanoparticles (NPs) as carriers for anti-cancer drugs have attracted interest due to their favorable properties, which include the enhanced permeability and retention effect. Silver NPs (AgNPs) have been explored as nanocarriers owing to their good conductivity, chemical stability, and therapeutic potential. In this study, AgNPs were synthesized, functionalized with chitosan (CS), and loaded with the anti-cancer drug cisplatin (CIS). Successful conjugation, size distribution, and morphology of the NPs were assessed by UV-vis and Fourier transform infra-red (FTIR) spectroscopy, NP tracking analysis (NTA), and transmission electron microscopy (TEM). The encapsulated CIS (>80%) was efficiently and rapidly released from the nanocomplex at low pH, favoring delivery to a tumor micro-environment. Cytotoxicity profiles of the CS-AgNP-CIS nanocomplexes exhibited significant cell death in the human breast cancer cell lines, MCF-7 and SKBR-3. They were more effective than the free drug, exhibiting >50% cell death. Our results demonstrate a potentially efficient anti-cancer drug delivery system with selectivity to breast cancer cells.

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