5-Fluorouracil induces apoptosis of colorectal cancer cells

Zhang, J T; Zhou, Wenli; He, Chuan; Liu, T; Li, C Y; Wang, L

doi:10.4238/gmr.15017326

Cited by 3 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 24 h, the cells were treated with OSR at different concentrations (100, 50, and 25 mg/l) for 1 to 7 days. The control group was incubated in a drug-free medium, and the positive group was exposed to 5-Fu (20 mg/l) ( 21 ). The number of surviving cells from each group was counted daily using Trypan Blue staining assay, according to the directions below.…”

Section: Methodsmentioning

confidence: 99%

Inï¿½vivo and inï¿½vitro induction of the apoptotic effects of oxysophoridine on colorectal cancer cells via the Bcl‑2/Bax/caspase-3 signaling pathway

Jin

Yang

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

Oxysophoridine (OSR) is a major active alkaloid extracted from Sophoraalopecuroides L. The aim of the present study was to investigate the induction of the apoptotic effects of OSR on colorectal cancer cells in vivo and in vitro. The results of the MTT and colony formation assays demonstrated that the proliferation of HCT116 cells was inhibited by OSR in vitro. The characteristics of cellular apoptosis in OSR-treated HCT116 cells were analyzed by Hoechst 33258 staining. It was also observed that the expression of caspase-3, B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and cytochrome c increased significantly upon OSR treatment. However, the expression of Bcl-2 and poly ADP-ribose polymerase-1 (PARP-1) was downregulated in OSR-treated cells compared with untreated cells. The in vivo experiments identified that OSR significantly inhibited the growth of the transplanted mouse CT26 tumor tissue, upregulated the expression of caspase-3, Bax and cytochrome c and downregulated the expression of Bcl-2 and PARP-1, as detected by reverse transcription-quantitative polymerase chain reaction and western blotting. It may be concluded that OSR significantly induced apoptotic effects on colorectal cancer cells in vivo and in vitro, and that its mechanism may be associated with the Bcl-2/Bax/caspase-3 signaling pathway.

show abstract

Section: Methodsmentioning

confidence: 99%

Inï¿½vivo and inï¿½vitro induction of the apoptotic effects of oxysophoridine on colorectal cancer cells via the Bcl‑2/Bax/caspase-3 signaling pathway

Jin

Yang

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…Around 500,000 people in China died from it just in 2015[3]. Although 5-Fu is often employed as chemotherapy against gastric cancer, its effect varies, likely due to the drug resistance of gastric tumors[10,11,27]. To overcome the problem of increasing drug resistance, 5-Fu is usually used with other compounds to enhance cancer cell sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…With a broad spectrum of activity against malignant cells, 5-ﬂuorouracil (5-Fu) is commonly employed against gastric, liver and colorectal cancers[6-8]. As a prevalent chemotherapeutic drug in clinical practice, 5-Fu can inhibit cancer cell proliferation and DNA replication, including gastric, breast and colorectal cancer cells, by inhibiting thymidylate synthase from synthesizing thymine, which ultimately induces apoptosis[9-11].…”

Section: Introductionmentioning

confidence: 99%

Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-ﬂuorouracil on gastric cancer cells through the AKT-mTOR pathway

Cui¹,

Li²,

Ren³

et al. 2019

WJG

View full text Add to dashboard Cite

BACKGROUND Gastric cancer is one of the most common and deadly malignancies worldwide. Despite recent medical progress, the 5-year survival rate of gastric cancer is still unsatisfactory. 5-ﬂuorouracil (5-Fu) is one of the first-line antineoplastic treatments for gastric cancer, as it can effectively induce cancer cell apoptosis. However, the effect of 5-Fu is limited due to drug resistance of the malignant tumor. Previous studies have reported that Sotetsuflavone from Cycas revoluta Thunb. can markedly suppress lung cancer cell proliferation by apoptosis, though its effect on gastric cancer remains unknown. AIM To investigate the inhibitory effect of Cycas revoluta Thunb. and to determine whether it can overcome gastric cancer cell drug resistance to 5-Fu. METHODS Cell viability was examined to determine whether the natural extract of Cycas revoluta Thunb. induced gastric cancer cell death. The half-maximal effective concentration and the half-maximal lethal concentration were calculatede. Wound-healing and transwell assays were performed to examine gastric cancer cell motility. Clonogenic assays were performed to investigate the synergistic effects of Cycas revoluta Thunb. with 5-Fu, and apoptotic bodies were detected by Hoechst staining. Western blotting was performed to examine the expression of related proteins and to investigate the molecular mechanism of Cycas revoluta Thunb.-induced cancer cell apoptosis. The expressions of proteins, including mammalian target of rapamycin (mTOR) and p-AKT, were detected in different combinations of treatments for 48 h, then analyzed by ECL detection. RESULTS Gastric cancer cells were more sensitive to the natural extract of Cycas revoluta Thunb. compared to normal gastric epithelial cells, and the extract effectively inhibited gastric cancer cell migration and invasion. The extract improved the anti-cancer effect of 5-Fu by enhancing the chemosensitization of gastric cancer cells. Extract plus 5-Fu further reduced the expression of the drug-resistance-related proteins p-AKT and mTOR after 48 h compared to 5-Fu alone. Compared to 5-Fu treatment alone, mTOR and p-AKT expression was significantly reduced by about 50% and 75%, respectively. We also found that the natural extract of Cycas revoluta Thunb. further increased 5-Fu-induced gastric cancer cell apoptosis. Expression of apoptosis-related protein X-linked inhibitor of apoptosis protein and apoptosis inducing factor were significantly reduced and increased, respectively, in the 5-Fu-resistant gastric cancer line SGC-7901/R treated with extract plus 5-Fu, while the expression of survivin did not change. CONCLUSION The natural extract of Cycas revoluta Thunb. effectively inhibit...

show abstract

“… 70 , 74 LGR4 is overexpressed in cancer cells, where it increases invasion, proliferation, survival, and resistance to 5-fluorouracil. 75 – 77 …”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance

Vert¹,

Castro²,

Ribó³

et al. 2018

OTT

View full text Add to dashboard Cite

BackgroundOvarian cancer has the highest mortality rate among all the gynecological cancers. This is mostly due to the resistance of ovarian cancer to current chemotherapy regimens. Therefore, it is of crucial importance to identify the molecular mechanisms associated with chemoresistance.MethodsNCI/ADR-RES is a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer. We carried out a microarray-derived transcriptional profiling analysis of NCI/ADR-RES to identify differentially expressed genes relative to its parental OVCAR-8.ResultsGene-expression profiling has allowed the identification of genes and pathways that may be important for the development of drug resistance in ovarian cancer. The NCI/ADR-RES cell line has differential expression of genes involved in drug extrusion, inactivation, and efficacy, as well as genes involved in the architectural and functional reorganization of the extracellular matrix. These genes are controlled through different signaling pathways, including MAPK–Akt, Wnt, and Notch.ConclusionOur findings highlight the importance of using orthogonal therapies that target completely independent pathways to overcome mechanisms of resistance to both classical chemotherapeutic agents and molecularly targeted drugs.

show abstract

5-Fluorouracil induces apoptosis of colorectal cancer cells

Cited by 3 publications

References 19 publications

Inï¿½vivo and inï¿½vitro induction of the apoptotic effects of oxysophoridine on colorectal cancer cells via the Bcl‑2/Bax/caspase-3 signaling pathway

Inï¿½vivo and inï¿½vitro induction of the apoptotic effects of oxysophoridine on colorectal cancer cells via the Bcl‑2/Bax/caspase-3 signaling pathway

Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-ﬂuorouracil on gastric cancer cells through the AKT-mTOR pathway

Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance

Contact Info

Product

Resources

About