scholarly journals Natural Peptides Inducing Cancer Cell Death: Mechanisms and Properties of Specific Candidates for Cancer Therapeutics

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7453
Author(s):  
Plinio A. Trinidad-Calderón ◽  
Carlos Daniel Varela-Chinchilla ◽  
Silverio García-Lara
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Treatment Options ◽  
Cancer Therapeutics ◽  
New Drugs ◽  
Tumor Cell Death ◽  
Cancer Cell Death ◽  
Anticancer Effects ◽  
Cell Death Mechanisms

Nowadays, cancer has become the second highest leading cause of death, and it is expected to continue to affect the population in forthcoming years. Additionally, treatment options will become less accessible to the public as cases continue to grow and disease mechanisms expand. Hence, specific candidates with confirmed anticancer effects are required to develop new drugs. Among the novel therapeutic options, proteins are considered a relevant source, given that they have bioactive peptides encrypted within their sequences. These bioactive peptides, which are molecules consisting of 2–50 amino acids, have specific activities when administered, producing anticancer effects. Current databases report the effects of peptides. However, uncertainty is found when their molecular mechanisms are investigated. Furthermore, analyses addressing their interaction networks or their directly implicated mechanisms are needed to elucidate their effects on cancer cells entirely. Therefore, relevant peptides considered as candidates for cancer therapeutics with specific sequences and known anticancer mechanisms were accurately reviewed. Likewise, those features which turn certain peptides into candidates and the mechanisms by which peptides mediate tumor cell death were highlighted. This information will make robust the knowledge of these candidate peptides with recognized mechanisms and enhance their non-toxic capacity in relation to healthy cells and further avoid cell resistance.

Molecular Mechanisms of the Action of Myricetin in Cancer

2020 ◽  
Vol 20 (2) ◽  
pp. 123-133 ◽  
Author(s):  
Yutao Xie ◽  
Yunlong Wang ◽  
Wei Xiang ◽  
Qiaoying Wang ◽  
Yajun Cao
Keyword(s):  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
New Drugs ◽  
Natural Pigment ◽  
Cancer Cell Death ◽  
Anticancer Effects ◽  
Anticancer Mechanism ◽  
Solid Foundation ◽  
Intracellular Activities ◽  
Myrica Nagi

Natural compounds, such as paclitaxel and camptothecin, have great effects on the treatment of tumors. Such natural chemicals often achieve anti-tumor effects through a variety of mechanisms. Therefore, it is of great significance to conduct further studies on the anticancer mechanism of natural anticancer agents to lay a solid foundation for the development of new drugs. Myricetin, originally isolated from Myrica nagi, is a natural pigment of flavonoids that can inhibit the growth of cancer cells (such as liver cancer, rectal cancer, skin cancer and lung cancer, etc.). It can regulate many intracellular activities (such as anti-inflammatory and blood lipids regulation) and can even be bacteriostatic. The purpose of this paper is to outline the molecular pathways of the anticancer effects of myricetin, including the effect on cancer cell death, proliferation, angiogenesis, metastasis and cell signaling pathway.

scholarly journals Tocotrienols Modulate a Life or Death Decision in Cancers

2019 ◽  
Vol 20 (2) ◽  
pp. 372 ◽  
Author(s):  
Shiau-Ying Tham ◽  
Hwei-San Loh ◽  
Chun-Wai Mai ◽  
Ju-Yen Fu
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Promising Alternative ◽  
Cancer Cell Death ◽  
Survival Pathways ◽  
Cell Death Mechanisms ◽  
A Minor

Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.

scholarly journals Primary and Secondary Cone Cell Death Mechanisms in Inherited Retinal Diseases and Potential Treatment Options

2022 ◽  
Vol 23 (2) ◽  
pp. 726
Author(s):  
Alicia A. Brunet ◽  
Alan R. Harvey ◽  
Livia S. Carvalho
Keyword(s):  
Quality Of Life ◽  
Cell Death ◽  
Effective Treatment ◽  
Treatment Options ◽  
Retinal Diseases ◽  
Potential Treatment ◽  
Cone Cell ◽  
Similarities And Differences ◽  
Cell Death Mechanisms

Inherited retinal diseases (IRDs) are a leading cause of blindness. To date, 260 disease-causing genes have been identified, but there is currently a lack of available and effective treatment options. Cone photoreceptors are responsible for daylight vision but are highly susceptible to disease progression, the loss of cone-mediated vision having the highest impact on the quality of life of IRD patients. Cone degeneration can occur either directly via mutations in cone-specific genes (primary cone death), or indirectly via the primary degeneration of rods followed by subsequent degeneration of cones (secondary cone death). How cones degenerate as a result of pathological mutations remains unclear, hindering the development of effective therapies for IRDs. This review aims to highlight similarities and differences between primary and secondary cone cell death in inherited retinal diseases in order to better define cone death mechanisms and further identify potential treatment options.

scholarly journals Quantitative Ultrasound Characterization of Tumor Cell Death: Ultrasound-Stimulated Microbubbles for Radiation Enhancement

2021 ◽  
Author(s):  
Raffi Karshafian ◽  
Hyunjung Christina Kim ◽  
Azza Al-Mahrouki ◽  
Alborz Gorjizadeh ◽  
Ali Sadeghi-Naini ◽  
...  
Keyword(s):  
Cell Death ◽  
Quantitative Ultrasound ◽  
Radiation Effects ◽  
Severe Combined Immunodeficiency ◽  
Cyclophilin A ◽  
Tumor Cell Death ◽  
Backscatter Intensity ◽  
Non Invasive ◽  
Cancer Cell Death ◽  
Ultrasound Backscatter

The aim of this study was to assess the efficacy of quantitative ultrasound imaging in characterizing cancer cell death caused by enhanced radiation treatments. This investigation focused on developing this ultrasound modality as an imaging-based non-invasive method that can be used to monitor therapeutic ultrasound and radiation effects. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human prostate xenografts grown in severe combined immunodeficiency (SCID) mice were treated using 8, 80, or 1000 µL/kg of microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. The increase in backscatter intensity compared to the control ranged from 1.9±1.6 dB for the clinical imaging dose of microbubbles (8 µL/kg, 250 kPa, 2 Gy) to 7.0±4.1 dB for the most extreme treatment condition (1000 µL/kg, 750 kPa, 8 Gy). In parallel, in situ end-labelling (ISEL) staining, ceramide, and cyclophilin A staining demonstrated increases in cell death due to DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a result of cell membrane permeabilization, respectively. Quantitative ultrasound results indicated changes that paralleled increases in cell death observed from histology analyses supporting its use for non-invasive monitoring of cancer treatment outcomes.

Targeting of cancer cell death mechanisms by resveratrol: a review

APOPTOSIS ◽  
2021 ◽  
Author(s):  
Xiao Fu ◽  
Mu Li ◽  
Cuilian Tang ◽  
Zezhi Huang ◽  
Masoud Najafi
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Cancer Cell Death ◽  
Cell Death Mechanisms

Cell Death Mechanisms Induced by INNO-406, a Novel Tyrosine Kinase Inhibitor for Imatinib-Resistant Ph+ Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2177-2177
Author(s):  
Yuri Kamitsuji ◽  
Souichi Adachi ◽  
Motonobu Watanabe ◽  
Hiroshi Matsubara ◽  
Yasuhiro Mizushima ◽  
...  
Keyword(s):  
Cell Death ◽  
Dna Fragmentation ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cellular Growth ◽  
Caspase Activity ◽  
Apoptosis Pathway ◽  
Cell Death Mechanisms

Abstract The blockade of Bcr-Abl signaling suppresses cellular growth and induces cell death in Bcr-Abl-positive (Bcr-Abl+) cells. We herein assessed the cell death mechanisms induced by INNO-406 (formerly NS-187; Kimura et al, Blood 2005), in four CML-derived Bcr-Abl+ cell lines (K562, KT-1, BV173 and MYL), and Ba/F3 harboring wild type bcr-abl (Ba/F3/wt bcr-abl). When cells are treated by INNO-406, the accumulation of subG1 fraction was seen in all five cell lines. This cell death was accompanied by loss of mitochondrial membrane potential and was inhibited by over-expression of Bcl-2, indicating that INNO-406-induced cell death is mainly mediated by mitochondria-dependent apoptosis. Caspase-3 activation in INNO-406-treated cell was also common among all cell lines. However, the inhibition of caspase activity by ZVAD-fmk (ZVAD), a pan-caspase inhibitor, was variable in the cell lines tested. In K562, KT-1 and BV173 cells treated with INNO-406, ZVAD almost completely prevented apoptosis (i.e. showing atypical feature for apoptosis, no DNA fragmentation and no accumulation of subG1 fraction), with cell death resulting from morphologically non-apoptotic cell death. The percentages of non-apoptotic cells under ZVAD co-treated with INNO-406 varied among the three cell lines, suggesting that the dependence on non-apoptotic cell death is variable. While, in MYL and Ba/F3/wt bcr-abl cells, despite the sufficient inhibition of caspases’ activity, the inhibition of the cell death by ZVAD was only partial and these cell lines still underwent apoptosis (i.e. showing DNA fragmentation and the accumulation of subG1 population), suggesting the presence of caspase-independent apoptotic machineries. In addition, assay data for apoptosome activities (complex of Apaf-1, cytochrome c and caspase-9 that initiates and drives cysteine protease activities of caspase in mitochondrial-mediated pathway) suggested that cell types could be largely subdivided into two groups, namely those cells with high apoptosome activity (K562, KT-1 and BV173) that undergo non-apoptotic, and, those cells with low apoptosome activity (MYL and Ba/F3/wt bcr-abl.) that undergo caspase-independent apoptosis when caspase activity was blocked by ZVAD. These data indicate that there is a common initial pathway for cell death due to INNO-406, while the pathway for cell death commitment (i.e. dependence on apoptosome/caspases-mediated apoptosis pathway that has been commonly believed to be central for apoptosis execution) vary among cellular context in Bcr-Abl+ leukemic cells. Moreover, in a mouse model of primary human CML in blast crisis, INNO-406 caused cell death with fragmented nuclei typical to apoptosis and “necklace-like” nuclei not typical of apoptosis, further implicating the significance of involvement of caspase-independent, non-apoptotic cell death in vivo. Further studies of the role of caspase-independent cell death in patient-derived Bcr-Abl+ cells and the molecular mechanisms that lead to mitochondrial-depolarization and caspase-independent apoptotic and/or non-apoptotic cell death may help the development of novel therapeutic strategies against Bcr-Abl+ leukemias.

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