Cannabis sativa L. Extracts can reverse drug resistance in colorectal carcinoma cells in vitro

Synergy ◽  
2019 ◽  
Vol 9 ◽  
pp. 100056 ◽  
Author(s):  
Innocensia Mokgohlwe Mangoato ◽  
Chandrashekara Puthanapura Mahadevappa ◽  
Motlalepula Gilbert Matsabisa
1997 ◽  
Vol 25 (2) ◽  
pp. 264S-264S ◽  
Author(s):  
ROBERT BREW ◽  
JOHN S. ERIKSON ◽  
DAVID C. WEST ◽  
BRIAN F. FLANAGAN ◽  
STEPHEN E. CHRISTMAS

2021 ◽  
Author(s):  
Andjela Franich ◽  
◽  
Milica Dimitrijević Stojanović ◽  
Snežana Rajković ◽  
Marina Jovanović ◽  
...  

Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is anion of malonic (mal, Pt1), 2-methylmalonic (Me-mal, Pt2), 2,2-dimethylmalonic (Me2-mal, Pt3) or 1,1- cyclobutanedicarboxylic (CBDCA, Pt4) acid while 5,6-epoxy-1,10-phen is bidentately coordinated 5,6-epoxy-5,6-dihydro-1,10-phenanthroline were synthesized and characterized by elemental microanalysis, IR, UV-Vis and NMR (1H and 13C) spectroscopic techniques. In vitro anticancer activity of novel platinum(II) complexes have been investigated on human and murine cancer cell lines, as well as normal murine cell line by MTT assay. The obtained results indicate that studied platinum(II) complexes exhibited strong cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. Complex Pt3 display stronger selectivity toward carcinoma cells in comparison to other tested platinum(II) complexes exhibiting beneficial antitumor activity mainly via the induction of apoptosis, as well as inhibition of cell proliferation and migration. Further study showed that Pt3 complex also carry significant in vivo antitumor activity in orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All results imply that these novel platinum(II) complexes have a good anti-tumor effect on breast and colorectal cancer in vivo and in vitro and the affinity to become possible candidates for treatment in anticancer therapy.


2006 ◽  
Vol 12 (20) ◽  
pp. 6194-6202 ◽  
Author(s):  
Manjinder Kaur ◽  
Rana P. Singh ◽  
Mallikarjuna Gu ◽  
Rajesh Agarwal ◽  
Chapla Agarwal

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Lin Wang ◽  
Xueting Wang ◽  
Tong Wang ◽  
Yingping Zhuang ◽  
Guan Wang

AbstractCervical cancer is a serious health problem in women around the globe. However, the use of clinical drug is seriously dampened by the development of drug resistance. Efficient in vitro tumor model is essential to improve the efficiency of drug screening and the accuracy of clinical application. Multicellular tumor spheroids (MTSs) can in a way recapitulates tumor traits in vivo, thereby representing a powerful transitional model between 2D monolayer culture and xenograft. In this study, based on the liquid overlay method, a protocol for rapid generation of the MTSs with uniform size and high reproducibility in a high-throughput manner was established. As expected, the cytotoxicity results showed that there was enhanced 5-fluorouracil (5-FU) resistance of HeLa carcinoma cells in 3D MTSs than 2D monolayer culture with a resistance index of 5.72. In order to obtain a holistic view of the molecular mechanisms that drive 5-FU resistance in 3D HeLa carcinoma cells, a multi-omics study was applied to discover hidden biological regularities. It was observed that in the 3D MTSs mitochondrial function-related proteins and the metabolites of the tricarboxylic acid cycle (TCA cycle) were significantly decreased, and the cellular metabolism was shifted towards glycolysis. The differences in the protein synthesis, processing, and transportation between 2D monolayer cultures and 3D MTSs were significant, mainly in the heat shock protein family, with the up-regulation of protein folding function in endoplasmic reticulum (ER), which promoted the maintenance of ER homeostasis in the 3D MTSs. In addition, at the transcript and protein level, the expression of extracellular matrix (ECM) proteins (e.g., laminin and collagen) were up-regulated in the 3D MTSs, which enhanced the physical barrier of drug penetration. Summarizing, this study formulates a rapid, scalable and reproducible in vitro model of 3D MTS for drug screening purposes, and the findings establish a critical role of glycolytic metabolism, ER hemostasis and ECM proteins expression profiling in tumor chemoresistance of HeLa carcinoma cells towards 5-FU. Graphical Abstract


2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Alfina Grasso ◽  
Margherita Ferrante ◽  
Massimo Libra ◽  
Rossella Salemi ◽  
Angelo Dimartino ◽  
...  

2019 ◽  
Vol 20 (8) ◽  
pp. 1917 ◽  
Author(s):  
Yixuan Xia ◽  
Chu Shing Lam ◽  
Wanfei Li ◽  
Md. Shahid Sarwar ◽  
Kanglun Liu ◽  
...  

Natural products, explicitly medicinal plants, are an important source of inspiration of antitumor drugs, because they contain astounding amounts of small molecules that possess diversifying chemical entities. For instance, Isodon (formerly Rabdosia), a genus of the Lamiaceae (formerly Labiatae) family, has been reported as a rich source of natural diterpenes. In the current study, we evaluated the in vitro anti-proliferative property of flexicaulin A (FA), an Isodon diterpenoid with an ent-kaurane structure, in human carcinoma cells, by means of cell viability assay, flow cytometric assessment, quantitative polymerase chain reaction array, Western blotting analysis, and staining experiments. Subsequently, we validated the in vivo antitumor efficacy of FA in a xenograft mouse model of colorectal carcinoma. From our experimental results, FA appears to be a potent antitumor molecule, since it significantly attenuated the proliferation of human colorectal carcinoma cells in vitro and restricted the growth of corresponsive xenograft tumors in vivo without causing any adverse effects. Regarding its molecular mechanism, FA considerably elevated the expression level of p21 and induced cell cycle arrest in the human colorectal carcinoma cells. While executing a non-apoptotic mechanism, we believe the antitumor potential of FA opens up new horizons for the therapy of colorectal malignancy.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3600 ◽  
Author(s):  
Anca Laura Maghiari ◽  
Dorina Coricovac ◽  
Iulia Andreea Pinzaru ◽  
Ioana Gabriela Macașoi ◽  
Iasmina Marcovici ◽  
...  

Aspartame (ASP), an artificial sweetener abundantly consumed in recent years in an array of dietary products, has raised some concerns in terms of toxicity, and it was even suggested a link with the risk of carcinogenesis (colorectal cancer), though the present scientific data are rather inconclusive. This study aims at investigating the potential role of aspartame in colorectal cancer by suggesting two experimental approaches: (i) an in vitro cytotoxicity screening in HT-29 human colorectal carcinoma cells based on cell viability (Alamar blue assay), cell morphology and cell migration (scratch assay) assessment and (ii) an in ovo evaluation in terms of angiogenic and irritant potential by means of the chorioallantoic membrane method (CAM). The in vitro results showed a dose-dependent cytotoxic effect, with a significant decrease of viable cells at the highest concentrations tested (15, 30 and 50 mM) and morphological cellular changes. In ovo, aspartame (15 and 30 mM) proved to have a pro-angiogenic effect and a weak irritant potential at the vascular level. These data suggest new directions of research regarding aspartame’s role in colorectal cancer.


2009 ◽  
Vol 279 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Eleonora Costantino ◽  
Francesca Maddalena ◽  
Serena Calise ◽  
Annamaria Piscazzi ◽  
Virginia Tirino ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Ding ◽  
Mengxiong Li ◽  
Liuzhi Deng ◽  
Tian Li

Objective. To study the biological characteristics of paclitaxel resistant endometrial carcinoma cells and its mechanism of drug resistance.Method. The paclitaxel resistant cell lines were established by high-dose paclitaxel (TAX) injection. The IC50 of paclitaxel was determined by CCK-8 assay in Ishikawa and Ishikawa-TAX. The cell cycle and apoptosis rate were detected by flow cytometry. Western blot was used to detect the expression of p-AKT and p-p70S6K. The expression of drug resistance-related genes Pgp and MDR1 was determined by RT-PCR. Cell viability was determined by soft agarose assay and invasive ability in vitro by transwell assay.Results. Paclitaxel and NVP-BEZ235 cotreatment group can further inhibit the clonogenicity and invasion of Ishikawa and Ishikawa-TAX cells compared with paclitaxel alone and NVP-BEZ235 treatment group. Paclitaxel and NVP-BEZ235 cotreated groups increased the apoptosis rate of Ishikawa and increased G0/G1 phase arrest in both cells. Paclitaxel alone significantly inhibited p-AK and p-p70 S6K protein expression in Ishikawa and Ishikawa-TAX cells and the inhibition was enhanced by NVP-BEZ235 when cotreated with paclitaxel.Conclusion. Paclitaxel can inhibit Ishikawa and Ishikawa-TAX cell via PI3K/Akt/mTOR signaling pathway. Paclitaxel and NVP-BEZ235 cotreatment can enhance the inhibitory effect.


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