Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: Insight into chemobrain

Drug resistance among microbial pathogens and oxidative stress caused by reactive oxygen species are two of the most challenging global issues. Firstly, drug-resistant pathogens cause several fatalities every year. Secondly aging and a variety of diseases, such as cardiovascular disease and cancer, are associated with free radical generated oxidative stress. The treatments currently available are limited, ineffective, or less efficient, so there is an immediate need to tackle these issues by looking for new therapies to resolve resistance and neutralize the harmful effects of free radicals. In the 21st century, the best way to save humans from them could be by using plants as well as their bioactive constituents. In this specific context, Jasminum is a major plant genus that is used in the Ayurvedic system of medicine to treat a variety of ailments. The information in this review was gathered from a variety of sources, including books, websites, and databases such as Science Direct, PubMed, and Google Scholar. In this review, a total of 14 species of Jasminum have been found to be efficient and effective against a wide variety of microbial pathogens. In addition, 14 species were found to be active free radical scavengers. The review is also focused on the disorders related to oxidative stress, and it was concluded that Jasminum grandiflorum and J. sambac normalized various parameters that were elevated by free radical generation. Alkaloids, flavonoids (rutoside), terpenes, phenols, and iridoid glucosides are among the main phytoconstituents found in various Jasminum species. Furthermore, this review also provides insight into the mechanistic basis of drug resistance, the generation of free radicals, and the role of Jasminum plants in combating resistance and neutralizing free radicals.

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

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210623104227 ◽

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.

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Dysregulated Pyrimidine Biosynthesis Contributes to 5-FU Resistance in SCLC Patient-Derived Organoids but Response to a Novel Polymeric Fluoropyrimidine, CF10

Cancers ◽

10.3390/cancers12040788 ◽

2020 ◽

Vol 12 (4) ◽

pp. 788 ◽

Cited By ~ 3

Author(s):

William H. Gmeiner ◽

Lance D. Miller ◽

Jeff W. Chou ◽

Anthony Dominijanni ◽

Lysette Mutkus ◽

...

Keyword(s):

Drug Target ◽

Pyrimidine Biosynthesis ◽

Cancer Drug ◽

Rna Seq ◽

Novel Approach ◽

Anti Cancer ◽

New Treatments ◽

Insight Into ◽

Sclc Patient ◽

Identify Gene Expression

Chemo-immunotherapy is central to the treatment of small cell lung cancer (SCLC). Despite modest progress made with the addition of immunotherapy, current cytotoxic regimens display minimal survival benefit and new treatments are needed. Thymidylate synthase (TS) is a well-validated anti-cancer drug target, but conventional TS inhibitors display limited clinical efficacy in refractory or recurrent SCLC. We performed RNA-Seq analysis to identify gene expression changes in SCLC biopsy samples to provide mechanistic insight into the potential utility of targeting pyrimidine biosynthesis to treat SCLC. We identified systematic dysregulation of pyrimidine biosynthesis, including elevated TYMS expression that likely contributes to the lack of efficacy for current TS inhibitors in SCLC. We also identified E2F1-3 upregulation in SCLC as a potential driver of TYMS expression that may contribute to tumor aggressiveness. To test if TS inhibition could be a viable strategy for SCLC treatment, we developed patient-derived organoids (PDOs) from human SCLC biopsy samples and used these to evaluate both conventional fluoropyrimidine drugs (e.g., 5-fluorouracil), platinum-based drugs, and CF10, a novel fluoropyrimidine polymer with enhanced TS inhibition activity. PDOs were relatively resistant to 5-FU and while moderately sensitive to the front-line agent cisplatin, were relatively more sensitive to CF10. Our studies demonstrate dysregulated pyrimidine biosynthesis contributes to drug resistance in SCLC and indicate that a novel approach to target these pathways may improve outcomes.

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New insight into the role of MDMX in MDM2-mediated p53 degradation and anti-cancer drug development

Oncoscience ◽

10.18632/oncoscience.542 ◽

2021 ◽

Vol 8 ◽

pp. 94-96

Author(s):

Jing Yang ◽

Yanping Zhang

Keyword(s):

Drug Development ◽

Cancer Drug ◽

Anti Cancer ◽

Insight Into

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Improving anti-cancer drug delivery performance of magnetic mesoporous silica nanocarriers for more efficient colorectal cancer therapy

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01056-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Sonia Iranpour ◽

Ahmad Reza Bahrami ◽

Sirous Nekooei ◽

Amir Sh. Saljooghi ◽

Maryam M. Matin

Keyword(s):

Colorectal Cancer ◽

Drug Delivery ◽

Side Effects ◽

Mesoporous Silica ◽

Cancer Drug ◽

Delivery Performance ◽

Anti Cancer ◽

Cancer Drug Delivery ◽

Magnetic Mesoporous Silica ◽

Ht 29

Abstract Background Improving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs. Materials and methods Herein, we designed a novel DDS based on magnetic mesoporous silica core–shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors. Results Nanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects. Conclusion These results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy. Graphic abstract

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Bioorthogonal Photo-Catalytic Activation of an Anti-Cancer Prodrug by Riboflavin

10.33774/chemrxiv-2021-pcw03-v3 ◽

2021 ◽

Author(s):

Xin Yang ◽

Limin Ma ◽

Hongwei Shao ◽

Xia Ling ◽

Mengyu Yao ◽

...

Keyword(s):

Side Effects ◽

Cancer Treatment ◽

Density Functional ◽

Cancer Drug ◽

Spatiotemporal Resolution ◽

Precise Control ◽

Catalytic Activation ◽

Anti Cancer

Chemotherapies for cancer treatment usually suffer from poor targeting ability and serious side-effects. To improve the treatment efficiency and reduce side effects, photoactivatable chemotherapy has been recently proposed for precise cancer treatment with high spatiotemporal resolution. However, most photoactivatable prodrugs require decoration by stoichiometric photo-cleavable groups, which are only responsive to ultraviolet irradiation and suffer from low reaction efficiency. To tackle these challenges, we herein propose a bioorthogonal photo-catalytic activation strategy with riboflavin as the catalyst for in situ transformation of prodrug dihydrochelerythrine (DHCHE) prodrug into anti-cancer drug chelerythrine (CHE), which can efficiently kill cancer cells and inhibit in vivo tumor growth under light irradiation. Meanwhile, the photo-catalytic transformation from DHCHE into CHE was in situ monitored by green-to-red fluorescence conversion, which can be used for precise control of the therapeutic dose. The photocatalytic mechanism was also fully explored by means of density functional theory (DFT) calculations. We believe this imaging-guided bioorthogonal photo-catalytic activation strategy is promising for cancer chemotherapy in clinical applications.

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Current progress and future perspectives in the development of anti-polo-like kinase 1 therapeutic agents

F1000Research ◽

10.12688/f1000research.11398.1 ◽

2017 ◽

Vol 6 ◽

pp. 1024 ◽

Cited By ~ 11

Author(s):

Jung-Eun Park ◽

David Hymel ◽

Terrence R. Burke, Jr. ◽

Kyung S. Lee

Keyword(s):

Side Effects ◽

Cancer Therapeutics ◽

Current Status ◽

Cancer Drug ◽

Mitotic Progression ◽

Cancer Drug Discovery ◽

Anti Cancer ◽

Tumor Specificity ◽

The Subject ◽

New Generation

Although significant levels of side effects are often associated with their use, microtubule-directed agents that primarily target fast-growing mitotic cells have been considered to be some of the most effective anti-cancer therapeutics. With the hope of developing new-generation anti-mitotic agents with reduced side effects and enhanced tumor specificity, researchers have targeted various proteins whose functions are critically required for mitotic progression. As one of the highly attractive mitotic targets, polo-like kinase 1 (Plk1) has been the subject of an extensive effort for anti-cancer drug discovery. To date, a variety of anti-Plk1 agents have been developed, and several of them are presently in clinical trials. Here, we will discuss the current status of generating anti-Plk1 agents as well as future strategies for designing and developing more efficacious anti-Plk1 therapeutics.

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5-Fluorouracil—Complete Insight into Its Neutral and Ionised Forms

Molecules ◽

10.3390/molecules24203683 ◽

2019 ◽

Vol 24 (20) ◽

pp. 3683 ◽

Cited By ~ 2

Author(s):

Justyna Wielińska ◽

Andrzej Nowacki ◽

Beata Liberek

Keyword(s):

Gas Phase ◽

Cancer Drug ◽

Mesomeric Effect ◽

Deprotonated Form ◽

Dft Methods ◽

Charge Delocalization ◽

Tautomeric Forms ◽

Anti Cancer ◽

Ph Range ◽

Insight Into

5-Fluorouracil (5FU), a common anti-cancer drug, occurs in four tautomeric forms and possesses two potential sites of both protonation and deprotonation. Tautomeric and resonance structures of the ionized forms of 5FU create the systems of connected equilibriums. Since there are contradictory reports on the ionized forms of 5FU in the literature, complex theoretical studies on neutral, protonated and deprotonated forms of 5FU, based on the broad spectrum of DFT methods, are presented. These indicate that the O4 oxygen is more willingly protonated than the O2 oxygen and the N1 nitrogen is more willingly deprotonated than the N3 nitrogen in a gas phase. Such preferences are due to advantageous charge delocalization of the respective ions, which is demonstrated by the NBO and ESP analyses. In an aqueous phase, stability differences between respective protonated and deprotonated forms of 5FU are significantly diminished due to the competition between the mesomeric effect and solvation. The calculated pKa values of the protonated, neutral and singly deprotonated 5FU indicate that 5FU does not exist in the protonated and double-deprotonated forms in the pH range of 0–14. The neutral form dominates below pH 8 and the N1 deprotonated form dominates above pH 8.

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Stimuli Responsive Nanoparticles for Controlled Anti-cancer Drug Release

Current Medicinal Chemistry ◽

10.2174/0929867325666180111095913 ◽

2018 ◽

Vol 25 (16) ◽

pp. 1837-1866 ◽

Cited By ~ 29

Author(s):

Qi Tang ◽

Bing Yu ◽

Lilong Gao ◽

Hailin Cong ◽

Na Song ◽

...

Keyword(s):

Side Effects ◽

Drug Release ◽

Cancer Chemotherapy ◽

Material Science ◽

Cancer Drug ◽

Stimuli Responsive ◽

The Past ◽

Anti Cancer ◽

Stimuli Response ◽

Therapeutic Responses

Conventional drugs used for cancer chemotherapy have severe toxic side effects and show individually varied therapeutic responses. The convergence of nanotechnology, biology, material science and pharmacy offers a perspective strategy for cancer chemotherapy. Nanoparticles loaded with anti-cancer drug have been designed to overcome the limitations associated with conventional drugs, several nanomedicines have been approved by FDA and shown good performances in clinical practice. However, the therapeutic efficacies cannot be enhanced. Taking this into account, stimuli responsive nanoparticles present the ability to enhance therapeutic efficacy and reduce side effects. In this review, we systematically summarized the recent progresses of controlled anti-cancer drug release systems based on nanoparticles with different stimuli response including pH, temperature, light, redox and others. If the achievements of the past can be extrapolated into the future, it is highly likely that responsive nanoparticles with a wide array of desirable properties can be eventually developed for safe and efficient cancer therapy.

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Current Insight into the Therapeutic Potential of Phytocompounds and their Nanoparticle-based Systems for Effective Management of Lung Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210708123750 ◽

2021 ◽

Vol 21 ◽

Author(s):

Mahak Fatima ◽

Mohammad Kashif Iqubal ◽

Ashif Iqubal ◽

Harsimran Kaur ◽

Sadaf Jamal Gilani ◽

...

Keyword(s):

Lung Cancer ◽

Side Effects ◽

Targeted Delivery ◽

Therapeutic Potential ◽

Cycle Arrest ◽

Alternative Therapeutic Approach ◽

Anti Cancer ◽

Insight Into ◽

Cell Signaling Pathways ◽

Cancer Activity

: Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At present, various treatment approaches are available such as chemotherapy, surgery, and radiotherapy. However, all these approaches usually cause serious side effects like degeneration of normal cells, bone marrow depression, alopecia, extensive vomiting, etc. To overcome the aforementioned problems, researchers have focused on the alternative therapeutic approach in which various natural compounds are reported, which possessed anti-lung cancer activity. Phytocompounds exhibit their anti-lung cancer activity via targeting various cell-signaling pathways, apoptosis, cell cycle arrest, and regulating antioxidant status and detoxification. Apart from the excellent anti-cancer activity, clinical administration of phytocompounds is confined because of their high lipophilicity and low bioavailability. Therefore, researchers show their concern in the development of a stable, safe, and effective approach of treatment with minimal side effects by the development of nanoparticle-based delivery of these phytocompounds to the target site. Targeted delivery of phytocompound through nanoparticles overcomes the aforementioned problems. In this article, the molecular mechanism of phytocompounds, their emerging combination therapy, and their nanoparticles-based delivery systems in the treatment of lung cancer have been discussed.

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