scholarly journals Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications

2018 ◽  
Vol 19 (9) ◽  
pp. 2752 ◽  
Author(s):  
Ibrahim El Halabi ◽  
Rachelle Bejjany ◽  
Rihab Nasr ◽  
Deborah Mukherji ◽  
Sally Temraz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Ascorbic Acid ◽  
Cancer Cells ◽  
Warburg Effect ◽  
Tumour Regression ◽  
Therapeutic Concept ◽  
Therapeutic Benefits ◽  
Potential Benefits ◽  
The Warburg Effect

Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cancer patients, there is merit in further exploring this therapeutic concept. In this review, we discuss the potential benefits of intravenous AA administration on colorectal cancer and we specifically focus on its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation, BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level, colorectal cancer cells undergo a metabolic shift called the Warburg effect to allow for more glucose absorption and utilization of glycolysis. This shift also allows AA to enter which leads to a disruption in the Warburg effect and a shutdown of the downstream KRAS pathway in mutated KRAS colon cancer cells. At the clinical level, AA is associated with tumour regression in advanced disease and improved tolerability and side effects of standard therapy. Based on these findings, we conclude that further clinical trials are needed on a larger scale to examine the therapeutic benefits of AA in colon cancer.

scholarly journals Positive feedback of DDX6/c-Myc/PTB1 regulated by miR-124 contributes to maintenance of the Warburg effect in colon cancer cells

2015 ◽  
Vol 1852 (9) ◽  
pp. 1971-1980 ◽  
Author(s):  
Kohei Taniguchi ◽  
Nobuhiko Sugito ◽  
Minami Kumazaki ◽  
Haruka Shinohara ◽  
Nami Yamada ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Positive Feedback ◽  
Warburg Effect ◽  
Colon Cancer Cells ◽  
The Warburg Effect

scholarly journals Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Elise Saunier ◽  
Samantha Antonio ◽  
Anne Regazzetti ◽  
Nicolas Auzeil ◽  
Olivier Laprévote ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Warburg Effect ◽  
Pyruvate Dehydrogenase Complex ◽  
Colon Cancer Cells ◽  
Dehydrogenase Complex ◽  
The Warburg Effect

Importance of the Microbiota Inhibitory Mechanism on the Warburg Effect in Colorectal Cancer Cells

2019 ◽  
Vol 51 (3) ◽  
pp. 738-747 ◽  
Author(s):  
Majid Eslami ◽  
Sina Sadrifar ◽  
Mohsen Karbalaei ◽  
Masoud Keikha ◽  
Nazarii M. Kobyliak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Warburg Effect ◽  
Inhibitory Mechanism ◽  
Colorectal Cancer Cells ◽  
The Warburg Effect

Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review

2017 ◽  
Vol 18 (9) ◽  
Author(s):  
Mohadeseh Hasanpourghadi ◽  
Chung Yeng Looi ◽  
Ashok Kumar Pandurangan ◽  
Gautam Sethi ◽  
Won Fen Wong ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
The Warburg Effect

Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect

2018 ◽  
Vol 1870 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Linchong Sun ◽  
Caixia Suo ◽  
Shi-ting Li ◽  
Huafeng Zhang ◽  
Ping Gao
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
Metabolic Reprogramming ◽  
The Warburg Effect

scholarly journals Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1261
Author(s):  
Nurul Fattin Che Rahim ◽  
Yazmin Hussin ◽  
Muhammad Nazirul Mubin Aziz ◽  
Nurul Elyani Mohamad ◽  
Swee Keong Yeap ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Lines ◽  
Curcuma Longa ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Sw620 Cell

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.

scholarly journals Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

scholarly journals Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Helena de Castro e Gloria ◽  
Laura Jesuíno Nogueira ◽  
Patrícia Bencke Grudzinski ◽  
Paola Victória da Costa Ghignatti ◽  
Temenouga Nikolova Guecheva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Mismatch Repair ◽  
Cell Cycle Progression ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Colon ◽  
Human Colon Cancer

Abstract Background The advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved. Methods Human colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed. Results Our results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities. Conclusion Our results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

scholarly journals Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4417
Author(s):  
Rabin Neupane ◽  
Saloni Malla ◽  
Mariam Sami Abou-Dahech ◽  
Swapnaa Balaji ◽  
Shikha Kumari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colon Cancer Cells ◽  
Apoptotic Pathway ◽  
Anticancer Efficacy ◽  
Colon Cell ◽  
Ic50 Values ◽  
Induced Apoptosis

A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

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