scholarly journals Carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline as a cytotoxic agent against colorectal cancer

RSC Advances ◽  
2018 ◽  
Vol 8 (71) ◽  
pp. 40760-40764
Author(s):  
Boqiao Fu ◽  
Xiaolin Wang ◽  
Yingjie Li ◽  
Jingying Hu ◽  
Dai Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Agent ◽  
Normal Cells

We synthesized a carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline. It exhibited reduced cytotoxicity to normal cells, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla
Keyword(s):  
Adverse Effects ◽  
Anticancer Agents ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Normal Cells ◽  
Normal Tissues ◽  
Organ Specific ◽  
Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

Reverse Screening Bioinformatics Approach to Identify Potential Anti Breast Cancer Targets Using Thymoquinone from Neutraceuticals Black Cumin Oil

2019 ◽  
Vol 19 (5) ◽  
pp. 599-609 ◽  
Author(s):  
Sumathi Sundaravadivelu ◽  
Sonia K. Raj ◽  
Banupriya S. Kumar ◽  
Poornima Arumugamand ◽  
Padma P. Ragunathan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Death ◽  
In Silico ◽  
Chemotherapeutic Agents ◽  
Normal Cells ◽  
Black Cumin ◽  
In Silico Docking ◽  
Wide Range

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.

scholarly journals Smart Nanoparticles for Chemo-Based Combinational Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 853
Author(s):  
Binita Shrestha ◽  
Lijun Wang ◽  
Eric M. Brey ◽  
Gabriela Romero Uribe ◽  
Liang Tang
Keyword(s):  
Cancer Treatment ◽  
Cancer Biology ◽  
Complex Disease ◽  
Rapid Development ◽  
Acquired Resistance ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Combinational Therapy ◽  
Precision Therapy ◽  
External Stimuli

Cancer is a heterogeneous and complex disease. Traditional cancer therapy is associated with low therapeutic index, acquired resistance, and various adverse effects. With the increasing understanding of cancer biology and technology advancements, more strategies have been exploited to optimize the therapeutic outcomes. The rapid development and application of nanomedicine have motivated this progress. Combinational regimen, for instance, has become an indispensable approach for effective cancer treatment, including the combination of chemotherapeutic agents, chemo-energy, chemo-gene, chemo-small molecules, and chemo-immunology. Additionally, smart nanoplatforms that respond to external stimuli (such as light, temperature, ultrasound, and magnetic field), and/or to internal stimuli (such as changes in pH, enzymes, hypoxia, and redox) have been extensively investigated to improve precision therapy. Smart nanoplatforms for combinational therapy have demonstrated the potential to be the next generation cancer treatment regimen. This review aims to highlight the recent advances in smart combinational therapy.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

scholarly journals Histone methyltransferase WHSC1 inhibits colorectal cancer cell apoptosis via targeting anti-apoptotic BCL2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Wang ◽  
Liming Zhu ◽  
Mei Guo ◽  
Gang Sun ◽  
Kun Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
B Cell Lymphoma ◽  
Histone Methyltransferase ◽  
Chemotherapeutic Agents ◽  
Cancer Cell Apoptosis ◽  
Active Transcription

AbstractWHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. In this study, we revealed how WHSC1 regulates tumorigenesis and chemosensitivity of colorectal cancer (CRC). Our data showed that WHSC1 as well as H3K36me2 were highly expressed in clinical CRC samples, and high WHSC1 expression is associated with poorer prognosis in CRC patients. WHSC1 reduction promoted colon cancer cell apoptosis both in vivo and in vitro. We found that B cell lymphoma-2 (BCL2) expression, an anti-apoptotic protein, is markedly decreased in after WHSC1 depletion. Mechanistic characterization indicated that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level. What’s more, our study indicated that WHSC1 depletion promotes chemosensitivity in CRC cells. Together, our results suggested that WHSC1 and H3K36me2 modification might be optimal therapeutic targets to disrupt CRC progression and WHSC1-targeted therapy might potentially overcome the resistance of chemotherapeutic agents.

Natural-Derived Molecules as a Potential Adjuvant in Chemotherapy: Normal Cell Protectors and Cancer Cell Sensitizers

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Mohammad S. Mubarak ◽  
Divya Jain ◽  
Rasel Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Polyphenolic Compounds ◽  
Anticancer Effect ◽  
Anticancer Activities ◽  
Normal Cells ◽  
Anti Cancer ◽  
Global Threat

Background: Cancer is a global threat to humans and a leading cause of death worldwide. Cancer treatment includes, among other things, the use of chemotherapeutic agents, compounds that are vital for treating and preventing cancer. However, chemotherapeutic agents produce oxidative stress along with other side effects that would affect the human body. Objective: To reduce the oxidative stress of chemotherapeutic agents in cancer and normal cells by naturally derived compounds with anti-cancer properties, and protect normal cells from the oxidation process. Therefore, the need to develop more potent chemotherapeutics with fewer side effects has become increasingly important. Method: Recent literature dealing with the antioxidant and anticancer activities of the naturally naturally-derived compounds: morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin has been surveyed and examined in this review. For this, data were gathered from different search engines, including Google Scholar, ScienceDirect, PubMed, Scopus, Web of Science, Scopus, and Scifinder, among others. Additionally, several patient offices such as WIPO, CIPO, and USPTO were consulted to obtain published articles related to these compounds. Result: Numerous plants contain flavonoids and polyphenolic compounds such as morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin, which exhibit ‎antioxidant, anti-inflammatory, and anti-carcinogenic actions via several mechanisms. These compounds show sensitizers of cancer cells and protectors of healthy cells. Moreover, these compounds can reduce oxidative stress, which is accelerated by chemotherapeutics and exhibit a potent anticancer effect on cancer cells. Conclusions: Based on these findings, more research is recommended to explore and evaluate such flavonoids and polyphenolic compounds.

The Emerging Role of Metformin in the Prevention and Treatment of Colorectal Cancer: A Game Changer for Management of Colorectal Cancer

2021 ◽  
Vol 18 ◽  
Author(s):  
Moein Ala
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Inflammation ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapeutic Agents ◽  
Advanced Adenoma ◽  
High Risk Population ◽  
Mesenchymal Transition ◽  
Cytotoxicity Activity ◽  
Increased Risk ◽  
Patients With Diabetes

: Metformin is an old, inexpensive and relatively safe anti-diabetic medication which can decrease the increased risk of several types of cancer in patients with diabetes. Recent meta-analyses revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cell cytotoxicity activity. It was uncovered that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreased the incidence of colonic adenoma in patients with acromegaly and reduced the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreased the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population.

scholarly journals Antiproliferative and Apoptotic Effects of Red Beetroot and Betanin on Human Colorectal Cancer Cell Lines

2021 ◽  
Author(s):  
Amir Saber ◽  
Nasim Abedimanesh ◽  
Mohammad-Hossein Somi ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Alcoholic Extract ◽  
Caspase 9 ◽  
Dapi Staining ◽  
Normal Cells ◽  
Colorectal Cancer Cell Lines ◽  
Ht 29

Abstract Background: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Fruit and vegetables have some active compounds such as flavonoids and polyphenols that protect against malignancies through their antioxidative, anti-inflammatory, anti-proliferative, neuro, and hepatoprotective properties. Red beetroot (Beta vulgaris) contains red (betacyanins) and yellow (betaxanthins) pigments known as betalains. Betanin makes up 75-95% of the total betacyanins, possessed a wide range of favorable biological effects such as chemopreventive, anticarcinogenic, anti-tumorogenic, antiangiogenic, and proapoptotic effects. Methods: Red beetroot hydro-alcoholic extract and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells, as well as KDR/293 normal epithelial cells. The half-maximal inhibitory concentration (IC50) was determined by prescreening MTT tests in the range of 20 to 140 µg/ml at 24 and 48 h. The cytotoxicity and apoptosis-inducing evaluations were performed via MTT assay, DAPI staining, and FACS-flow cytometry tests using determined times and doses. Moreover, the expression level of six important genes involving in the apoptosis pathway (Bcl-2, BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) were determined using the real-time polymerase chain reaction (RT-PCR) method.Results: The IC50 doses for HT-29 and Caco-2 cell lines were determined to be about 92 μg/mL, 107 μg/mL for beetroot hydro-alcoholic extract, and 64 μg/mL, 90 μg/mL for betanin at 48 h, respectively. Our findings showed that beetroot extract and betanin significantly inhibit the growth of HT-29 and Caco-2 cell lines, time and dose-dependently, without considerable adverse effects on KDR/293 normal cells. Moreover, DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. The expression level of pro-apoptotic genes involved in intrinsic and extrinsic apoptosis pathways (BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) in treated HT-29 and Caco-2 cells was higher than untreated and normal cells, whereas the anti-apoptotic gene (Bcl-2) was downregulated. Conclusion: Beetroot hydro-alcoholic extract and betanin significantly inhibited cell proliferation and induced cell apoptosis (intrinsic and extrinsic pathways) via modification of effective genes in both colorectal cancer cell lines with no significant cytotoxic effects on KDR/293 normal cells. The mechanism of the anticancer effects of red beetroot extract and betanin needs to be further studied.

scholarly journals Immunotherapy, Inflammation and Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 618 ◽  
Author(s):  
Charles Robert Lichtenstern ◽  
Rachael Katie Ngu ◽  
Shabnam Shalapour ◽  
Michael Karin
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
The United States ◽  
Chemotherapeutic Agents ◽  
Adoptive T Cell Therapy ◽  
Current Status ◽  
Cancer Type ◽  
T Cell Therapy

Colorectal cancer (CRC) is the third most common cancer type, and third highest in mortality rates among cancer-related deaths in the United States. Originating from intestinal epithelial cells in the colon and rectum, that are impacted by numerous factors including genetics, environment and chronic, lingering inflammation, CRC can be a problematic malignancy to treat when detected at advanced stages. Chemotherapeutic agents serve as the historical first line of defense in the treatment of metastatic CRC. In recent years, however, combinational treatment with targeted therapies, such as vascular endothelial growth factor, or epidermal growth factor receptor inhibitors, has proven to be quite effective in patients with specific CRC subtypes. While scientific and clinical advances have uncovered promising new treatment options, the five-year survival rate for metastatic CRC is still low at about 14%. Current research into the efficacy of immunotherapy, particularly immune checkpoint inhibitor therapy (ICI) in mismatch repair deficient and microsatellite instability high (dMMR–MSI-H) CRC tumors have shown promising results, but its use in other CRC subtypes has been either unsuccessful, or not extensively explored. This Review will focus on the current status of immunotherapies, including ICI, vaccination and adoptive T cell therapy (ATC) in the treatment of CRC and its potential use, not only in dMMR–MSI-H CRC, but also in mismatch repair proficient and microsatellite instability low (pMMR-MSI-L).

scholarly journals Over-Expression of βII-Tubulin and Especially Its Localization in Cell Nuclei Correlates with Poorer Outcomes in Colorectal Cancer

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 25 ◽  
Author(s):  
Kseniya Ruksha ◽  
Artur Mezheyeuski ◽  
Alexander Nerovnya ◽  
Tatyana Bich ◽  
Gennady Tur ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Cancer Progression ◽  
Nuclear Localization ◽  
Cancer Growth ◽  
Transformed Cells ◽  
Regulatory Pathway ◽  
Cell Nuclei ◽  
Normal Cells ◽  
Over Expression

Tubulin is a heterodimer of α and β subunits, both existing as isotypes differing in amino acid sequence encoded by different genes. Specific isotypes of tubulin have associations with cancer that are not well understood. Previous studies found that βII-tubulin is expressed in a number of transformed cells and that this isotype is found in cell nuclei in non-microtubule form. The association of βII expression and its nuclear localization with cancer progression has not previously been addressed. We here used a monoclonal antibody to βII to examine patients with colorectal cancer and found that patients whose tumors over-express βII have a greatly decreased life expectancy which is even shorter in those patients with nuclear βII. Our results suggest that βII-tubulin may facilitate cancer growth and metastasis and, to accomplish this, may not need to be in microtubule form. Furthermore, βII expression and localization could be a useful prognostic marker. We also found that βII appears in the nuclei of otherwise normal cells adjacent to the tumor. It is possible therefore that cancer cells expressing βII influence nearby cells to do the same and to localize βII in their nuclei by an as yet uncharacterized regulatory pathway.

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