scholarly journals Newly Obtained Apple Pectin as an Adjunct to Irinotecan Therapy of Colorectal Cancer Reducing E. coli Adherence and β-Glucuronidase Activity

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2952
Author(s):  
Anna Palko-Łabuz ◽  
Jerzy Maksymowicz ◽  
Beata Sobieszczańska ◽  
Agnieszka Wikiera ◽  
Magdalena Skonieczna ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Active Form ◽  
Apple Pectin ◽  
Promising Candidate ◽  
E Coli ◽  
Glucuronidase Activity ◽  
Induced Apoptosis ◽  
Species Production

Colorectal cancer (CRC) is the second cause of cancer death worldwide. The composition and enzymatic activity of colonic microbiota can significantly affect the effectiveness of CRC chemotherapy. Irinotecan is a drug widely used to treat colon cancer. However, the transformation of a drug-glucuronide (SN-38G) back to its active form (SN-38) by bacterial β-glucuronidase (GUS) constitutes the primary reason for the observed intestinal toxicity of irinotecan. It was demonstrated that novel enzymatically extracted apple pectin (PC) might be a promising candidate for an adjunct to irinotecan therapy. PC itself reduced the viability of HCT 116 and Caco-2 colorectal cancer cells, induced apoptosis, and increased intracellular reactive oxygen species production. Moreover, PC enhanced the cytotoxic and proapoptotic effect of irinotecan (at concentrations below its IC50), i.e., synergistic effect was recorded. Additionally, PC exhibited potent anti-inflammatory properties and prevented adhesion of prototype adherent-invasive E. coli (AIEC) LF82 strain and laboratory K-12C600 strain to colon cancer cells. PC was also identified to be an effective inhibitor of bacterial GUS activity. Altogether, novel apple pectin was identified as a promising candidate for a supplement to irinotecan therapy that might alleviate its side-effects via inhibition of bacterial GUS and thus increasing its therapeutic efficacy.

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.

scholarly journals Lemongrass Extract Possesses Potent Anticancer Activity Against Human Colon Cancers, Inhibits Tumorigenesis, Enhances Efficacy of FOLFOX, and Reduces Its Adverse Effects

2019 ◽  
Vol 18 ◽  
pp. 153473541988915 ◽  
Author(s):  
Ivan Ruvinov ◽  
Christopher Nguyen ◽  
Benjamin Scaria ◽  
Caleb Vegh ◽  
Ola Zaitoon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Human Colon ◽  
Dependent Manner ◽  
Anticancer Efficacy ◽  
Colon Cancers ◽  
Induced Apoptosis

Current chemotherapeutics for metastatic colorectal cancers have limited success and are extremely toxic due to nonselective targeting. Some natural extracts have been traditionally taken and have shown anticancer activity. These extracts have multiple phytochemicals that can target different pathways selectively in cancer cells. We have shown previously that lemongrass ( Cymbopogon citratus) extract is effective at inducing cell death in human lymphomas. However, the efficacy of lemongrass extract on human colorectal cancer has not been investigated. Furthermore, its interactions with current chemotherapies for colon cancer is unknown. In this article, we report the anticancer effects of ethanolic lemongrass extract in colorectal cancer models, and importantly, its interactions with FOLFOX and Taxol. Lemongrass extract induced apoptosis in colon cancer cells in a time and dose-dependent manner without harming healthy cells in vitro. Oral administration of lemongrass extract was well tolerated and effective at inhibiting colon cancer xenograft growth in mice. It enhanced the anticancer efficacy of FOLFOX and, interestingly, inhibited FOLFOX-related weight loss in animals given the combination treatment. Furthermore, feeding lemongrass extract to APCmin/+ transgenic mice led to the reduction of intestinal tumors, indicating its preventative potential. Therefore, this natural extract has potential to be developed as a supplemental treatment for colorectal cancer.

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 Anticancer effects of bifidobacteria on colon cancer cell lines

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zeinab Faghfoori ◽  
Mohammad Hasan Faghfoori ◽  
Amir Saber ◽  
Azimeh Izadi ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Rt Pcr ◽  
Anticancer Effects ◽  
Colon Cancer Cell Lines ◽  
Apoptotic Genes

Abstract Background Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and has uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using it as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines. Methods The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method. Results The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes. Conclusions In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.

scholarly journals The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2045
Author(s):  
Agnieszka Gornowicz ◽  
Anna Szymanowska ◽  
Mariusz Mojzych ◽  
Robert Czarnomysy ◽  
Krzysztof Bielawski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cathepsin B ◽  
Beclin 1 ◽  
Special Role ◽  
The Novel ◽  
Colon Cancer Cells ◽  
Sulfonamide Derivative

Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have anti-tumor activity in vitro and in vivo. The aim of the study was to synthesize a novel 1,2,4-triazine sulfonamide derivative and check its anticancer potential in DLD-1 and HT-29 colon cancer cells. The biological studies included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. The concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. We demonstrated that the novel compound was able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM-1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines. The novel compound represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim.

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