scholarly journals Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy

2020 ◽  
Vol 21 (21) ◽  
pp. 7941 ◽  
Author(s):  
Lanfeng Dong ◽  
Vinod Gopalan ◽  
Olivia Holland ◽  
Jiri Neuzil

Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.

Author(s):  
Masahide Takahashi ◽  
Hiroki Kobayashi ◽  
Yasuyuki Mizutani ◽  
Akitoshi Hara ◽  
Tadashi Iida ◽  
...  

Fibroblasts synthesise the extracellular matrix (ECM) such as collagen and elastin, the excessive accumulation of which can lead to fibrosis and organ dysfunction under pathological conditions. Cancer-associated fibroblasts (CAFs) are major constituents of the tumour microenvironment (TME) that accompany the desmoplastic reaction responsible for anti-cancer treatment resistance. Thus, it is important to dissect the roles of CAFs in the TME to develop new therapeutic strategies for refractory cancers. Recent progress in the studies of CAF biology suggests that the functions of CAFs are complicated and that they are composed of functionally distinct populations, including cancer-promoting CAFs (pCAFs) and cancer-restraining CAFs (rCAFs). We recently identified a new cell surface marker for rCAFs in pancreatic and colon cancers, designated as Meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue)/Islr (immunoglobulin super family containing leucine-rich repeat). Based on the distribution of Meflin/Islr-positive cells, we also considered it a specific candidate marker for mesenchymal stroma/stem cells. Meflin/Islr-positive CAFs have been shown to suppress cancer progression by being involved in regulating collagen structures and BMP signalling in the TME. This review describes the function of Meflin/Islr in cancer fibrosis as well as in cardiac and lung fibrosis and its potential in the development of new cancer therapeutics.


2020 ◽  
Vol 20 (7) ◽  
pp. 758-767 ◽  
Author(s):  
Sepideh Izadi ◽  
Afshin Nikkhoo ◽  
Mohammad Hojjat-Farsangi ◽  
Afshin Namdar ◽  
Gholamreza Azizi ◽  
...  

Breast cancer has been identified as one of the main cancer-related deaths among women during some last decades. Recent advances in the introduction of novel potent anti-cancer therapeutics in association with early detection methods led to a decrease in the mortality rate of breast cancer. However, the scenario of breast cancer is yet going on and further improvements in the current anti-cancer therapeutic approaches are needed. Several factors are present in the tumor microenvironment which help to cancer progression and suppression of anti-tumor responses. Targeting these cancer-promoting factors in the tumor microenvironment has been suggested as a potent immunotherapeutic approach for cancer therapy. Among the various tumorsupporting factors, Cyclin-Dependent Kinases (CDKs) are proposed as a novel promising target for cancer therapy. These factors in association with cyclins play a key role in cell cycle progression. Dysregulation of CDKs which leads to increased cell proliferation has been identified in various cancers, such as breast cancer. Accordingly, the development and use of CDK-inhibitors have been associated with encouraging results in the treatment of breast cancer. However, it is unknown that the inhibition of which CDK is the most effective strategy for breast cancer therapy. Since the selective blockage of CDK1 alone or in combination with other therapeutics has been associated with potent anti-cancer outcomes, it is suggested that CDK1 may be considered as the best CDK target for breast cancer therapy. In this review, we will discuss the role of CDK1 in breast cancer progression and treatment.


2018 ◽  
Vol 25 (9) ◽  
pp. 1046-1054 ◽  
Author(s):  
Suet H. Ow ◽  
Pei J. Chua ◽  
Boon H. Bay

Background: MicroRNAs (miRNAs) are frequently dysregulated in cancers and serve as attractive targets for prognostication and therapeutic applications. Besides cancer, the biological functions of miR-149 have been studied in various diseases. This review aims to summarize the reports available in the literature, regarding miR-149 as a molecular target for cancer therapeutics. Methods: An extensive literature search was conducted using the Pubmed database to sieve out articles related to the roles of miR-149 in carcinogenesis and cancer progression, and potential miRNA-based therapies. A total of 89 publications were selected for inclusion in this review. Results: Depending on the cancer type, miR-149 can behave either as a tumor suppressor or as an ‘onco-miR' that promotes tumorigenesis and cancer spread, suggesting that this miRNA has diverse functions. Potential miRNA-based therapies include the use of miRNA mimics, miRNA inhibitors, demethylating agents and circular RNAs. Conclusion: Although targeting miRNA is an attractive anti-cancer strategy, not all cancers can be treated by the same miRNA-based strategy. A comprehensive understanding of miRNA regulatory mechanism is also necessary to improve the design of miRNA-based therapeutics and there is a need for safe and efficient delivery methods when using this approach for anti-cancer treatment.


2019 ◽  
Vol 18 (30) ◽  
pp. 2555-2566 ◽  
Author(s):  
Bhaswati Chatterjee

The resistance to chemotherapeutics by the cancerous cells has made its treatment more complicated. Animal venoms have emerged as an alternative strategy for anti-cancer therapeutics. Animal venoms are cocktails of complex bioactive chemicals mainly disulfide-rich proteins and peptides with diverse pharmacological actions. The components of venoms are specific, stable, and potent and have the ability to modify their molecular targets thus making them good therapeutics candidates. The isolation of cancer-specific components from animal venoms is one of the exciting strategies in anti-cancer research. This review highlights the identified venom peptides and proteins from different venomous animals like snakes, scorpions, spiders, bees, wasps, snails, toads, frogs and sea anemones and their anticancer activities including inhibition of proliferation of cancer cells, their invasion, cell cycle arrest, induction of apoptosis and the identification of involved signaling pathways.


2015 ◽  
Vol 15 (7) ◽  
pp. 869-880 ◽  
Author(s):  
Guang-Chun Sun ◽  
X Yang ◽  
Yan Yu ◽  
Dai-Wei Zhao

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Kristell Le Gal ◽  
Clotilde Wiel ◽  
Mohamed X. Ibrahim ◽  
Marcus Henricsson ◽  
Volkan I. Sayin ◽  
...  

Cancer cells produce high levels of mitochondria-associated reactive oxygen species (ROS) that can damage macromolecules, but also promote cell signaling and proliferation. Therefore, mitochondria-targeted antioxidants have been suggested to be useful in anti-cancer therapy, but no studies have convincingly addressed this question. Here, we administered the mitochondria-targeted antioxidants MitoQ and MitoTEMPO to mice with BRAF-induced malignant melanoma and KRAS-induced lung cancer, and found that these compounds had no impact on the number of primary tumors and metastases; and did not influence mitochondrial and nuclear DNA damage levels. Moreover, MitoQ and MitoTEMPO did not influence proliferation of human melanoma and lung cancer cell lines. MitoQ and its control substance dTPP, but not MitoTEMPO, increased glycolytic rates and reduced respiration in melanoma cells; whereas only dTPP produced this effect in lung cancer cells. Our results do not support the use of mitochondria-targeted antioxidants for anti-cancer monotherapy, at least not in malignant melanoma and lung cancer.


Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 987
Author(s):  
Eric J. O’Neill ◽  
Deborah Termini ◽  
Alexandria Albano ◽  
Evangelia Tsiani

Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.


2021 ◽  
Vol 22 (2) ◽  
pp. 518
Author(s):  
Adam James Ferrari ◽  
Ronny Drapkin ◽  
Rajan Gogna

Cell competition (CC) is a feature that allows tumor cells to outcompete and eliminate adjacent cells that are deemed less fit. Studies of CC, first described in Drosophila melanogaster, reveal a diversity of underlying mechanisms. In this review, we will discuss three recent studies that expand our understanding of the molecular features governing CC. In particular, we will focus on a molecular fitness fingerprint, oncogenic pathways, and the importance of cell junction stability. A fitness fingerprint, mediated by flower (hFWE) protein isoforms, dictates that cells expressing the flower-win isoforms will outcompete adjacent flower-loss-expressing cells. The impact of the flower protein isoforms is seen in cancer progression and may have diagnostic potential. The yes-associated protein (YAP) and TAZ transcription factors, central mediators of the oncogenic Hippo pathway, elevate peritumoral fitness thereby protecting against tumor progression and provide a suppressive barrier. Similarly, COL17A1 is a key component in hemidesmosome stability, and its expression in epidermal stem cells contributes to fitness competition and aging characteristics. The contributions of these pathways to disease development and progression will help define how CC is hijacked to favor cancer growth. Understanding these features will also help frame the diagnostic and therapeutic possibilities that may place CC in the crosshairs of cancer therapeutics.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Khuram Shahzad Ahmad ◽  
Muntaha Talat ◽  
Shaan Bibi Jaffri ◽  
Neelofer Shaheen

AbstractConventional treatment modes like chemotherapy, thermal and radiations aimed at cancerous cells eradication are marked by destruction pointing the employment of nanomaterials as sustainable and auspicious materials for saving human lives. Cancer has been deemed as the second leading cause of death on a global scale. Nanomaterials employment in cancer treatment is based on the utilization of their inherent physicochemical characteristics in addition to their modification for using as nano-carriers and nano-vehicles eluted with anti-cancer drugs. Current work has reviewed the significant role of different types of nanomaterials in cancer therapeutics and diagnostics in a systematic way. Compilation of review has been done by analyzing voluminous investigations employing ERIC, MEDLINE, NHS Evidence and Web of Science databases. Search engines used were Google scholar, Jstore and PubMed. Current review is suggestive of the remarkable performance of nanomaterials making them candidates for cancer treatment for substitution of destructive treatment modes through investigation of their physicochemical characteristics, utilization outputs and long term impacts in patients.


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