The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction

Cancer is the world's second-largest cause of mortality and one of the biggest global health concerns. The prevalence and mortality rates of cancer remain high despite significant progress in cancer therapy. The search for more effective, as well as less toxic treatment methods for cancer, is at the focus of current studies. Thiophene and its derivatives have surged as an influential scaffold, which, because of their appreciable diversity in biological activities, has drawn the concerned interest of the researchers in the field of medicinal chemistry. By the affluent introduction of its derivatives, which have antioxidant, anti-inflammatory, antimicrobial, and anticancer activities, the adaptability of the thiophene moiety has been displayed. The nature and positioning of the substitutions significantly impacted thiophene moiety activity. This decent array in the living response account about this moiety has picked plentiful researcher’s consideration to inquire about it to its peculiar potential across certain activities. In the field of cancer therapy against different cancer cells, the structure-activity relationship for each of the derivatives showed an excellent understanding of thiophene moiety. Information from the various articles revealed the key role of thiophene moiety and its derivatives to develop the vital lead compound. The essential anticancer mechanisms identified include inhibition of the topoisomerase, inhibition of tyrosine kinase, tubulin interaction and apoptosis induction through the activation of reactive oxygen species. This review is an endeavor to promote the anticancer potential of the derivatives, whether having thiophene or condensed thiophene as a core moiety or as a substituent that can lead in the future to synthesize varieties of chemotherapeutic entities in the field of cancer treatment.

Download Full-text

Aurora Kinase Inhibitors in Head and Neck Cancer

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180112163741 ◽

2018 ◽

Vol 18 (3) ◽

pp. 199-213

Author(s):

Guangying Qi ◽

Jing Liu ◽

Sisi Mi ◽

Takaaki Tsunematsu ◽

Shengjian Jin ◽

...

Keyword(s):

Head And Neck Cancer ◽

Cancer Therapy ◽

Kinase Inhibitors ◽

Biological Function ◽

Aurora Kinase ◽

Aurora Kinases ◽

Related Research ◽

Chemotherapy Drugs ◽

Aurora Kinase Inhibitors

Aurora kinases are a group of serine/threonine kinases responsible for the regulation of mitosis. In recent years, with the increase in Aurora kinase-related research, the important role of Aurora kinases in tumorigenesis has been gradually recognized. Aurora kinases have been regarded as a new target for cancer therapy, resulting in the development of Aurora kinase inhibitors. The study and application of these small-molecule inhibitors, especially in combination with chemotherapy drugs, represent a new direction in cancer treatment. This paper reviews studies on Aurora kinases from recent years, including studies of their biological function, their relationship with tumor progression, and their inhibitors.

Download Full-text

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

Current Stem Cell Research & Therapy ◽

10.2174/1574888x13666180723104340 ◽

2019 ◽

Vol 14 (3) ◽

pp. 219-225 ◽

Cited By ~ 6

Author(s):

Cong Tang ◽

Guodong Zhu

Keyword(s):

Cancer Therapy ◽

Tyrosine Kinase ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Cell Receptor ◽

Transmembrane Receptors ◽

Biological Responses ◽

Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

Download Full-text

Cancer Fighting SiRNA-RRM2 Loaded Nanorobots

Pharmaceutical Nanotechnology ◽

10.2174/2211738508666200128120142 ◽

2020 ◽

Vol 8 (2) ◽

pp. 79-90

Author(s):

Arjun Sharma ◽

Pravir Kumar ◽

Rashmi K. Ambasta

Keyword(s):

Cancer Therapy ◽

Dna Synthesis ◽

Cancer Progression ◽

Sirna Delivery ◽

Predictive Marker ◽

The Body ◽

Tumor Site ◽

Target Delivery ◽

Target Effect

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.

Download Full-text

Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy

Molecular Cancer ◽

10.1186/s12943-020-01197-3 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 7

Author(s):

Yuanjun Lu ◽

Yau-Tuen Chan ◽

Hor-Yue Tan ◽

Sha Li ◽

Ning Wang ◽

...

Keyword(s):

Cancer Therapy ◽

Epigenetic Regulation ◽

Potential Role ◽

Human Cancer

Download Full-text

Photocontrolled apoptosis induction using precursor miR-664a and an RNA carrier-conjugated with photosensitizer

Scientific Reports ◽

10.1038/s41598-021-94249-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kazunori Watanabe ◽

Tomoko Nawachi ◽

Ruriko Okutani ◽

Takashi Ohtsuki

Keyword(s):

Cancer Therapy ◽

Cell Types ◽

Drug Candidate ◽

Apoptosis Induction ◽

Delivery Method ◽

Apoptotic Pathway ◽

Photochemical Internalization ◽

Therapeutic Uses ◽

Induction Of Apoptosis ◽

Nucleic Acid Drug

AbstractMethods to spatially induce apoptosis are useful for cancer therapy. To control the induction of apoptosis, methods using light, such as photochemical internalization (PCI), have been developed. We hypothesized that photoinduced delivery of microRNAs (miRNAs) that regulate apoptosis could spatially induce apoptosis. In this study, we identified pre-miR-664a as a novel apoptosis-inducing miRNA via mitochondrial apoptotic pathway. Further, we demonstrated the utility of photoinduced cytosolic dispersion of RNA (PCDR), which is an intracellular RNA delivery method based on PCI. Indeed, apoptosis is spatially regulated by pre-miR-664a and PCDR. In addition, we found that apoptosis induced by pre-miR-664a delivered by PCDR was more rapid than that by lipofection. These results suggest that pre-miR-664a is a nucleic acid drug candidate for cancer therapy and PCDR and pre-miR-664a-based strategies have potential therapeutic uses for diseases affecting various cell types.

Download Full-text

Description of the role of pharmacist independent double checks during cognitive order verification of outpatient parenteral anti-cancer therapy

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155221994319 ◽

2021 ◽

pp. 107815522199431

Author(s):

Jennifer P Booth ◽

Julie M Kennerly-Shah ◽

Amber D Hartman

Keyword(s):

Cancer Therapy ◽

Medication Error ◽

Retrospective Analysis ◽

Error Reporting ◽

Single Center ◽

Medication Error Reporting ◽

Anti Cancer ◽

Secondary Endpoints ◽

Type Frequency

Introduction To describe pharmacist interventions as a result of an independent double check during cognitive order verification of outpatient parenteral anti-cancer therapy. Methods A single-center, retrospective analysis of all individual orders for outpatient, parenteral anti-cancer agents within a hematology/oncology infusion center during a 30 day period was conducted. The primary endpoint was error identification rates during first and second verification. Secondary endpoints included the type, frequency, and severity of errors identified during second verification using a modified National Coordinating Council for Medication Error Reporting and Prevention Index. Results A total of 1970 anti-cancer parenteral orders were screened, from which 1645 received an independent double check and were included. The number of errors identified during first and second verification were 30 (1.8%) and 10 (0.6%) respectively; second verification resulted in a 33.3% increase in corrected errors. The 10 errors identified during second verification included: four rate transcriptions to optimize pump interoperability, three rate and/or volume modifications, two dosage adjustments, and one treatment deferral due to toxicity. The severity was classified as Category A for four (40%), Category C for three (30%), and Category D for three (30%) errors. This correlated to a low capacity for harm for seven (70%) and a serious capacity for three (30%) errors. Conclusions Second verification of outpatient, parenteral anti-cancer medication orders resulted in a 33.3% increase in corrected errors. Three errors detected during second verification were determined to have a serious capacity for harm, supporting the value of independent double checks during pharmacist cognitive order verification.

Download Full-text

The role of Notch ligand, Delta-like ligand 4 (DLL4), in cancer angiogenesis—implications for therapy

European Surgery ◽

10.1007/s10353-021-00707-x ◽

2021 ◽

Author(s):

Marlena Brzozowa-Zasada

Keyword(s):

Cancer Therapy ◽

Notch Signalling ◽

Signalling Pathway ◽

Gamma Secretase ◽

Tumour Angiogenesis ◽

Notch Signalling Pathway ◽

Expression Levels ◽

Blocking Agents ◽

Anti Cancer

Summary Background It is generally accepted that angiogenesis is a complex and tightly regulated process characterized by the growth of blood vessels from existing vasculature. Activation of the Notch signalling pathway affects multiple aspects of vascular development. One of the components of the Notch signalling pathway, Delta-like ligand 4 (DLL4), has recently appeared as a critical regulator of tumour angiogenesis and thus as a promising therapeutic target. Methods This review article includes available data from peer-reviewed publications associated with the role of DLL4 in cancer angiogenesis. Searches were performed in PubMed, EMBASE, Google Scholar and Web of Science using the terms “tumour angiogenesis”, “DLL4”, “Notch signalling” and “anti-cancer therapy”. Results The survival curves of cancer patients revealed that the patients with high DLL4 expression levels had significantly shorter survival times than the patients with low DLL4 expression. Moreover, a positive correlation was also identified between DLL4 and VEGF receptorsʼ expression levels. It seems that inhibition of DLL4 may exert potent growth inhibitory effects on some tumours resistant to anti-VEGF therapies. A great number of blocking agents of DLL4/Notch signalling including anti-DLL4 antibodies, DNA vaccination, Notch antibodies and gamma-secretase inhibitors have been studied in preclinical tumour models. Conclusion DLL4 seems to be a promising target in anti-cancer therapy. Nevertheless, the careful evaluation of adverse effects on normal physiological processes in relation to therapeutic doses of anti-DLL4 drugs will be significant for advancement of DLL4 blocking agents in clinical oncology.

Download Full-text

Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Cancers ◽

10.3390/cancers13112795 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2795

Author(s):

Sofia Papanikolaou ◽

Aikaterini Vourda ◽

Spyros Syggelos ◽

Kostis Gyftopoulos

Keyword(s):

Prostate Cancer ◽

Cancer Therapy ◽

Tumor Progression ◽

Epithelial Mesenchymal Transition ◽

Metastatic Tumor ◽

Therapy Resistance ◽

Cellular Process ◽

Cell Plasticity ◽

Mesenchymal Transition

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

Download Full-text

The Multifaceted Role of Flavonoids in Cancer Therapy: Leveraging Autophagy with a Double-Edged Sword

Antioxidants ◽

10.3390/antiox10071138 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1138

Author(s):

Zhe Zhang ◽

Jiayan Shi ◽

Edouard C. Nice ◽

Canhua Huang ◽

Zheng Shi

Keyword(s):

Cancer Therapy ◽

Dosage Forms ◽

Pharmacological Effects ◽

Autophagy Flux ◽

Normal Tissues ◽

Anti Cancer ◽

New Perspective ◽

New Research ◽

Cancer Activity

Flavonoids are considered as pleiotropic, safe, and readily obtainable molecules. A large number of recent studies have proposed that flavonoids have potential in the treatment of tumors by the modulation of autophagy. In many cases, flavonoids suppress cancer by stimulating excessive autophagy or impairing autophagy flux especially in apoptosis-resistant cancer cells. However, the anti-cancer activity of flavonoids may be attenuated due to the simultaneous induction of protective autophagy. Notably, flavonoids-triggered protective autophagy is becoming a trend for preventing cancer in the clinical setting or for protecting patients from conventional therapeutic side effects in normal tissues. In this review, focusing on the underlying autophagic mechanisms of flavonoids, we hope to provide a new perspective for clinical application of flavonoids in cancer therapy. In addition, we highlight new research ideas for the development of new dosage forms of flavonoids to improve their various pharmacological effects, establishing flavonoids as ideal candidates for cancer prevention and therapy in the clinic.

Download Full-text