scholarly journals Multifunctional Mitochondria-Targeting Nanosystems for Enhanced Anticancer Efficacy

2021 ◽  
Vol 9 ◽  
Author(s):  
Tingting Hu ◽  
Zhou Qin ◽  
Chao Shen ◽  
Han-Lin Gong ◽  
Zhi-Yao He
Keyword(s):  
Energy Source ◽  
Drug Resistance ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Layer Structure ◽  
Anticancer Efficacy ◽  
Subcellular Organelle ◽  
Novel Strategy ◽  
Mitochondria Targeting

Mitochondria, a kind of subcellular organelle, play crucial roles in cancer cells as an energy source and as a generator of reactive substrates, which concern the generation, proliferation, drug resistance, and other functions of cancer. Therefore, precise delivery of anticancer agents to mitochondria can be a novel strategy for enhanced cancer treatment. Mitochondria have a four-layer structure with a high negative potential, which thereby prevents many molecules from reaching the mitochondria. Luckily, the advances in nanosystems have provided enormous hope to overcome this challenge. These nanosystems include liposomes, nanoparticles, and nanomicelles. Here, we summarize the very latest developments in mitochondria-targeting nanomedicines in cancer treatment as well as focus on designing multifunctional mitochondria-targeting nanosystems based on the latest nanotechnology.

scholarly journals Drug-Like Small Molecule HSP27 Functional Inhibitor Sensitizes Lung Cancer Cells to Gefitinib or Cisplatin by Inducing Altered Cross-Linked Hsp27 Dimers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 630
Author(s):  
Hawon Yoo ◽  
Seul-Ki Choi ◽  
Jaeok Lee ◽  
So Hyeon Park ◽  
You Na Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Tumor Growth Inhibition ◽  
Dependent Manner ◽  
Hsp27 Expression ◽  
Cancer Aggressiveness

Relationships between heat shock protein 27 (HSP27) and cancer aggressiveness, metastasis, drug resistance, and poor patient outcomes in various cancer types including non-small cell lung cancer (NSCLC) were reported, and inhibition of HSP27 expression is suggested to be a possible strategy for cancer therapy. Unlike HSP90 or HSP70, HSP27 does not have an ATP-binding pocket, and no effective HSP27 inhibitors have been identified. Previously, NSCLC cancer cells were sensitized to radiation and chemotherapy when co-treated with small molecule HSP27 functional inhibitors such as zerumbone (ZER), SW15, and J2 that can induce abnormal cross-linked HSP27 dimer. In this study, cancer inhibition effects of NA49, a chromenone compound with better solubility, longer circulation time, and less toxicity than J2, were examined in combination with anticancer drugs such as cisplatin and gefitinib in NSCLC cell lines. When the cytotoxic drug cisplatin was treated in combination with NA49 in epidermal growth factor receptors (EGFRs) WT cell lines, sensitization was induced in an HSP27 expression-dependent manner. With gefitinib treatment, NA49 showed increased combination effects in both EGFR WT and Mut cell lines, also with HSP27 expression-dependent patterns. Moreover, NA49 induced sensitization in EGFR Mut cells with a secondary mutation of T790M when combined with gefitinib. Augmented tumor growth inhibition was shown with the combination of cisplatin or gefitinib and NA49 in nude mouse xenograft models. These results suggest the combination of HSP27 inhibitor NA49 and anticancer agents as a candidate for overcoming HSP27-mediated drug resistance in NSCLC patients.

Chalcone derivatives and their activities against drug-resistant cancers: An overview

2020 ◽  
Vol 20 ◽  
Author(s):  
Jiaqi Xiao ◽  
Meixiang Gao ◽  
Qiang Diao ◽  
Feng Gao
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Rational Design ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Chalcone Derivatives ◽  
Potential Activity ◽  
Defensive Mechanisms

: Drug resistance including multidrug resistance resulting from different defensive mechanisms in cancer cells is the leading cause of the failure about the cancer therapy, making it an urgent need to develop more effective anticancer agents. Chalcones, widely distributed in nature, could act on diverse enzymes and receptors in cancer cells. Accordingly, chalcone derivatives possess potential activity against various cancers including drug-resistant even multidrug-resistant cancer. This review outlines the recent development of chalcone derivatives with potential activity against drug-resistant cancers covering articles published between 2010 and 2020, so as to facilitate further rational design of more effective candidate.

scholarly journals Integrating Enzymatic Self-Assembly and Mitochondria Targeting for Selectively Killing Cancer Cells without Acquired Drug Resistance

2016 ◽  
Vol 138 (49) ◽  
pp. 16046-16055 ◽  
Author(s):  
Huaimin Wang ◽  
Zhaoqianqi Feng ◽  
Youzhi Wang ◽  
Rong Zhou ◽  
Zhimou Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Self Assembly ◽  
Acquired Drug Resistance ◽  
Mitochondria Targeting

scholarly journals Intra-mitochondrial biomineralization for inducing apoptosis of cancer cells

2018 ◽  
Vol 9 (9) ◽  
pp. 2474-2479 ◽  
Author(s):  
Sangpil Kim ◽  
L. Palanikumar ◽  
Huyeon Choi ◽  
M. T. Jeena ◽  
Chaekyu Kim ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Mitochondria Targeting ◽  
Potential Therapeutics

Mitochondria targeting mineralization can form biominerals inside cancerous mitochondria through concentration dependent silicification, resulting in dysfunction of mitochondria leading to apoptosis. These results suggest potential therapeutics for cancer treatment.

scholarly journals Imidazole-modified deferasirox encapsulated polymeric micelles as pH-responsive iron-chelating nanocarrier for cancer chemotherapy

RSC Advances ◽  
2017 ◽  
Vol 7 (18) ◽  
pp. 11158-11169 ◽  
Author(s):  
Man Theerasilp ◽  
Punlop Chalermpanapun ◽  
Kanyawan Ponlamuangdee ◽  
Dusita Sukvanitvichai ◽  
Norased Nasongkla
Keyword(s):  
Iron Deficiency ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Polymeric Micelles ◽  
Iron Level ◽  
Release Behavior ◽  
Ph Responsive ◽  
Cellular Iron ◽  
Novel Strategy

Modified deferasirox encapsulated polymeric micelles demonstrate pH-responsive and ON–OFF release behavior to deplete the iron level in cancer cells. The cellular iron deficiency is a novel strategy for cancer treatment.

scholarly journals TBX15/miR-152/KIF2C Pathway Regulates Breast Cancer Doxorubicin Resistance via Preventing PKM2 Ubiquitination

2020 ◽  
Author(s):  
Cheng-Fei Jiang ◽  
Yun-Xia Xie ◽  
Ying-Chen Qian ◽  
Min Wang ◽  
Ling-Zhi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Strategy Development ◽  
Luciferase Reporter ◽  
Doxorubicin Resistance ◽  
Novel Strategy ◽  
Cancer Tissues

Abstract BackgroundChemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer.MethodsAs measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were used to analyze the autophagy levels in vitro. By using online prediction software, luciferase reporter assays, co-Immunoprecipitation, Western blotting analysis and experimental animals models, we further elucidated the mechanisms.ResultsWe found TBX15 expression levels were decreased in Doxorubicin (DOX)-resistant breast cancer cells. Overexpression of TBX15 reversed the DOX resistance by inducing microRNA-152 (miR-152) expression. We found that KIF2C levels were highly expressed in DOX-resistant breast cancer tissues and cells, and KIF2C was a potential target of miR-152. TBX15 and miR-152 overexpression suppressed autophagy and glycolysis in breast cancer cells, while KIF2C overexpression reversed the process. Overexpression of KIF2C increased DOX resistance in cancer cells. Furthermore, KIF2C directly binds with PKM2 for inducing the DOX resistance. KIF2C can prevent the ubiquitination of PKM2 and increase its protein stability. In addition, we further identified that Domain-2 of KIF2C played a major role in the binding with PKM2 and preventing PKM2 ubiquitination, which enhanced DOX resistance by promoting autophagy and glycolysis. ConclusionsOur data identify a new mechanism by which TBX15 abolishes DOX chemoresistance in breast cancer, and suggest that TBX15/miR-152/KIF2C axis is a novel signaling pathway for mediating DOX resistance in breast cancer through regulating PKM2 ubiquitination and the enhancement of PKM2 stability. This finding suggests new therapeutic target and/or novel strategy development for cancer treatment to overcome drug resistance in the future.

scholarly journals The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 240 ◽  
Author(s):  
Phung Huong ◽  
Lap Nguyen ◽  
Xuan-Bac Nguyen ◽  
Sang Lee ◽  
Duc-Hiep Bach
Keyword(s):  
Drug Resistance ◽  
Growth Factors ◽  
Tumor Microenvironment ◽  
Treatment Failure ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Chemotherapeutic Drugs ◽  
Activated Platelets

Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet–cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.

scholarly journals Monofunctional Platinum(II) Anticancer Agents

2021 ◽  
Vol 14 (2) ◽  
pp. 133
Author(s):  
Suxing Jin ◽  
Yan Guo ◽  
Zijian Guo ◽  
Xiaoyong Wang
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Cancer Cells ◽  
General Formula ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Platinum Drugs ◽  
Cellular Distribution ◽  
Platinum Anticancer Drugs ◽  
Tumor Selectivity

Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side effects. Much effort has been made to circumvent the drug resistance and general toxicity of these drugs. Among multifarious designs, monofunctional platinum(II) complexes with a general formula of [Pt(3A)Cl]+ (A: Ammonia or amine) stand out as a class of “non-traditional” anticancer agents hopeful to overcome the defects of current platinum drugs. This review aims to summarize the development of monofunctional platinum(II) complexes in recent years. They are classified into four categories: fluorescent complexes, photoactive complexes, targeted complexes, and miscellaneous complexes. The intention behind the designs is either to visualize the cellular distribution, or to reduce the side effects, or to improve the tumor selectivity, or inhibit the cancer cells through non-DNA targets. The information provided by this review may inspire researchers to conceive more innovative complexes with potent efficacy to shake off the drawbacks of platinum anticancer drugs.

scholarly journals The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guangjian Fan ◽  
Lianhui Sun ◽  
Ling Meng ◽  
Chen Hu ◽  
Xing Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Drug Resistance ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Tumor Recurrence ◽  
Therapeutic Strategy ◽  
Regulatory Mechanisms ◽  
Therapeutic Resistance ◽  
Atr Kinases

AbstractDrug resistance and tumor recurrence are major challenges in cancer treatment. Cancer cells often display centrosome amplification. To maintain survival, cancer cells achieve bipolar division by clustering supernumerary centrosomes. Targeting centrosome clustering is therefore considered a promising therapeutic strategy. However, the regulatory mechanisms of centrosome clustering remain unclear. Here we report that KIFC1, a centrosome clustering regulator, is positively associated with tumor recurrence. Under DNA damaging treatments, the ATM and ATR kinases phosphorylate KIFC1 at Ser26 to selectively maintain the survival of cancer cells with amplified centrosomes via centrosome clustering, leading to drug resistance and tumor recurrence. Inhibition of KIFC1 phosphorylation represses centrosome clustering and tumor recurrence. This study identified KIFC1 as a prognostic tumor recurrence marker, and revealed that tumors can acquire therapeutic resistance and recurrence via triggering centrosome clustering under DNA damage stresses, suggesting that blocking KIFC1 phosphorylation may open a new vista for cancer therapy.

scholarly journals Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy

2018 ◽  
Vol 19 (8) ◽  
pp. 2256 ◽  
Author(s):  
Antoni Domagala ◽  
Klaudyna Fidyt ◽  
Malgorzata Bobrowicz ◽  
Joanna Stachura ◽  
Kacper Szczygiel ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Treatment Resistance ◽  
Metastatic Potential ◽  
Dependent Cell ◽  
And Function

Lysosomes are conservative organelles with an indispensable role in cellular degradation and the recycling of macromolecules. However, in light of recent findings, it has emerged that the role of lysosomes in cancer cells extends far beyond cellular catabolism and includes a variety of cellular pathways, such as proliferation, metastatic potential, and drug resistance. It has been well described that malignant transformation leads to alterations in lysosomal structure and function, which, paradoxically, renders cancer cells more sensitive to lysosomal destabilization. Furthermore, lysosomes are implicated in the regulation and execution of cell death in response to diverse stimuli and it has been shown that lysosome-dependent cell death can be utilized to overcome apoptosis and drug resistance. Thus, the purpose of this review is to characterize the role of lysosome in cancer therapy and to describe how these organelles impact treatment resistance. We summarized the characteristics of typical inducers of lysosomal cell death, which exert its function primarily via alterations in the lysosomal compartment. The review also presents other anticancer agents with the predominant mechanism of action different from lysosomal destabilization, the activity of which is influenced by lysosomal signaling, including classical chemotherapeutics, kinase inhibitors, monoclonal antibodies, as well as photodynamic therapy.

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