A Triple Co-Delivery Liposomal Carrier That Enhances Apoptosis via an Intrinsic Pathway in Melanoma Cells

The effectiveness of existing anti-cancer therapies is based mainly on the stimulation of apoptosis of cancer cells. Most of the existing therapies are somewhat toxic to normal cells. Therefore, the quest for nontoxic, cancer-specific therapies remains. We have demonstrated the ability of liposomes containing anacardic acid, mitoxantrone and ammonium ascorbate to induce the mitochondrial pathway of apoptosis via reactive oxygen species (ROS) production by the killing of cancer cells in monolayer culture and shown its specificity towards melanoma cells. Liposomes were prepared by a lipid hydration, freeze-and-thaw (FAT) procedure and extrusion through polycarbonate filters, a remote loading method was used for dug encapsulation. Following characterization, hemolytic activity, cytotoxicity and apoptosis inducing effects of loaded nanoparticles were investigated. To identify the anticancer activity mechanism of these liposomes, ROS level and caspase 9 activity were measured by fluorescence and by chemiluminescence respectively. We have demonstrated that the developed liposomal formulations produced a high ROS level, enhanced apoptosis and cell death in melanoma cells, but not in normal cells. The proposed mechanism of the cytotoxic action of these liposomes involved specific generation of free radicals by the iron ions mechanism.

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Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200310171547 ◽

2020 ◽

Vol 15 (6) ◽

pp. 482-491 ◽

Cited By ~ 1

Author(s):

Milena Kostadinova ◽

Milena Mourdjeva

Keyword(s):

Cancer Cells ◽

Small Population ◽

Tumor Formation ◽

Bioactive Molecules ◽

Cancer Therapies ◽

New Methods ◽

Cycle Arrest ◽

Anti Cancer ◽

Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

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Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666201020160348 ◽

2020 ◽

Vol 20 ◽

Author(s):

Milad Ashrafizadeh ◽

Shahram Taeb ◽

Hamed Haghi-Aminjan ◽

Shima Afrashi ◽

Kave Moloudi ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Fas Ligand ◽

Inhibitory Effect ◽

Mitochondrial Pathway ◽

Multi Drug Resistance ◽

Chemotherapy Drugs ◽

Normal Tissues ◽

Anti Cancer

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

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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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Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

Antioxidants ◽

10.3390/antiox9060532 ◽

2020 ◽

Vol 9 (6) ◽

pp. 532 ◽

Cited By ~ 7

Author(s):

Juhyun Shin ◽

Min-Ho Song ◽

Jae-Wook Oh ◽

Young-Soo Keum ◽

Ramesh Kumar Saini

Keyword(s):

Oxidative Stress ◽

Cancer Cells ◽

Apoptotic Cell ◽

Research Gaps ◽

Cytotoxic Effects ◽

Normal Cells ◽

Anti Cancer ◽

Antioxidant Function ◽

High Level ◽

Β Carotene

Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, β-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested.

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Therapeutic Perspectives of Molecules from Urtica dioica Extracts for Cancer Treatment

Molecules ◽

10.3390/molecules24152753 ◽

2019 ◽

Vol 24 (15) ◽

pp. 2753 ◽

Cited By ~ 8

Author(s):

Sabrina Esposito ◽

Alessandro Bianco ◽

Rosita Russo ◽

Antimo Di Maro ◽

Carla Isernia ◽

...

Keyword(s):

Natural Products ◽

Cancer Cells ◽

Current Knowledge ◽

Biological Activities ◽

Urtica Dioica ◽

Cancer Therapies ◽

Edible Plant ◽

Bioactive Natural Products ◽

Human Cancers ◽

Anti Cancer

A large range of chronic and degenerative diseases can be prevented through the use of food products and food bioactives. This study reports the health benefits and biological activities of the Urtica dioica (U. dioica) edible plant, with particular focus on its cancer chemopreventive potential. Numerous studies have attempted to investigate the most efficient anti-cancer therapy with few side effects and high toxicity on cancer cells to overcome the chemoresistance of cancer cells and the adverse effects of current therapies. In this regard, natural products from edible plants have been assessed as sources of anti-cancer agents. In this article, we review current knowledge from studies that have examined the cytotoxic, anti-tumor and anti-metastatic effects of U. dioica plant on several human cancers. Special attention has been dedicated to the treatment of breast cancer, the most prevalent cancer among women and one of the main causes of death worldwide. The anti-proliferative and apoptotic effects of U. dioica have been demonstrated on different human cancers, investigating the properties of U. dioica at cellular and molecular levels. The potent cytotoxicity and anti-cancer activity of the U. dioica extracts are due to its bioactive natural products content, including polyphenols which reportedly possess anti-oxidant, anti-mutagenic and anti-proliferative properties. The efficacy of this edible plant to prevent or mitigate human cancers has been demonstrated in laboratory conditions as well as in experimental animal models, paving the way to the development of nutraceuticals for new anti-cancer therapies.

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Antioxidant Defenses: A Context-Specific Vulnerability of Cancer Cells

Cancers ◽

10.3390/cancers11081208 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1208 ◽

Cited By ~ 3

Author(s):

Jordan A. Cockfield ◽

Zachary T. Schafer

Keyword(s):

Dna Damage ◽

Antioxidant Activity ◽

Cancer Cells ◽

Antioxidant Defenses ◽

Oxygen Species ◽

Normal Cells ◽

Anti Cancer ◽

Selective Elimination ◽

Specific Vulnerability ◽

Context Specific

Reactive oxygen species (ROS) are well known for their capacity to cause DNA damage, augment mutagenesis, and thereby promote oncogenic transformation. Similarly, agents that reduce ROS levels (antioxidants) are frequently thought to have anti-cancer properties given their propensity to minimize DNA damage and mutagenesis. However, numerous clinical studies focused on antioxidants suggest that this is a facile premise and that antioxidant capacity can be important for cancer cells in a similar fashion to normal cells. As a consequence of this realization, numerous laboratories have been motivated to investigate the biological underpinnings explaining how and when antioxidant activity can potentially be beneficial to cancer cells. Relatedly, it has become clear that the reliance of cancer cells on antioxidant activity in certain contexts represents a potential vulnerability that could be exploited for therapeutic gain. Here, we review some of the recent, exciting findings documenting how cancer cells utilized antioxidant activity and under what circumstances this activity could represent an opportunity for selective elimination of cancer cells.

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MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Cells ◽

10.3390/cells9010029 ◽

2019 ◽

Vol 9 (1) ◽

pp. 29 ◽

Cited By ~ 11

Author(s):

Hyun Ah Seo ◽

Sokviseth Moeng ◽

Seokmin Sim ◽

Hyo Jeong Kuh ◽

Soo Young Choi ◽

...

Keyword(s):

Cancer Therapy ◽

Combination Therapy ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Therapeutic Resistance ◽

Cancer Therapies ◽

Anti Cancer ◽

Different Types ◽

Therapeutic Responses

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

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The Influence of Tumor Microenvironment on Immune Escape of Melanoma

International Journal of Molecular Sciences ◽

10.3390/ijms21218359 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8359 ◽

Cited By ~ 4

Author(s):

Aleksandra Simiczyjew ◽

Ewelina Dratkiewicz ◽

Justyna Mazurkiewicz ◽

Marcin Ziętek ◽

Rafał Matkowski ◽

...

Keyword(s):

Tumor Microenvironment ◽

Immune Escape ◽

Cell Types ◽

Melanoma Cells ◽

Cancer Therapies ◽

System A ◽

Anti Cancer ◽

Low Efficiency ◽

Inflammatory Molecules

The low efficiency of currently-used anti-cancer therapies poses a serious challenge, especially in the case of malignant melanoma, a cancer characterized by elevated invasiveness and relatively high mortality rate. The role of the tumor microenvironment in the progression of melanoma and its acquisition of resistance to treatment seems to be the main focus of recent studies. One of the factors that, in normal conditions, aids the organism in its fight against the cancer and, following the malignant transformation, adapts to facilitate the development of the tumor is the immune system. A variety of cell types, i.e., T and B lymphocytes, macrophages, and dendritic and natural killer cells, as well as neutrophils, support the growth and invasiveness of melanoma cells, utilizing a plethora of mechanisms, including secretion of pro-inflammatory molecules, induction of inhibitory receptors expression, or depletion of essential nutrients. This review provides a comprehensive summary of the processes regulated by tumor-associated cells that promote the immune escape of melanoma cells. The described mechanisms offer potential new targets for anti-cancer treatment and should be further studied to improve currently-employed therapies.

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Ab Initio Studies of Anti-Cancer Drugs

Molecular Orbital Calculations for Biological Systems ◽

10.1093/oso/9780195098730.003.0011 ◽

1998 ◽

Author(s):

Anne-Marie Sapse

Keyword(s):

Cancer Therapy ◽

Ab Initio ◽

Cancer Cells ◽

Alkylating Agents ◽

Experimental Studies ◽

Chemotherapeutic Agents ◽

Theoretical Studies ◽

Cancer Drugs ◽

Normal Cells ◽

Anti Cancer

Cancer is an extraordinarily complicated group of diseases which are characterized by the loss of normal control of the maintenance of cellular organization in the tissues. It is still not completely understood how much of the disease is of genetic, viral, or environmental origin. The result, however, is that cancer cells possess growth advantages over normal cells, a reality which damages the host by local pressure effects, destruction of tissues, and secondary systemic effects. As such, a goal of cancer therapy is the destruction of cancer cells via chemotherapeutic agents or radiation. Since the late 1940s, when Farber treated leukemia with methotrexate, cancer therapy with cytotoxic drugs made enormous progress. Chemotherapy is usually integrated with other treatments such as surgery, radiotherapy, and immunotherapy, and it is clear that post-surgery, it is effective with solid tumors. This is due to the fact that only systemic therapy can attack micrometastases. The rationale for using chemotherapy is the control of tumor-cell populations via a killing mechanism. The major problem in this approach is the lack of selectivity of chemotherapeutic agents. Some agents indeed preferentially kill cancer cells, but no agents have been synthesized yet which kill only cancer cells and do not affect normal cells. Unfortunately, normal tissues are affected, giving rise to a multitude of side effects. In addition to drugs exhibiting cytotoxic activity, antiproliferative drugs are also formulated. According to their mode of action, anti-cancer drugs are divided into several classes. . . . alkylating agents antimetabolites DNA intercalators mitotic inhibitors lexitropsins drugs which bind covalently to DNA . . . Experimental studies of these molecules are complemented and enhanced by theoretical studies. Some of the theoretical studies use molecular mechanics methods while others apply ab initio or semi-empirical quantum-chemistry methods. Most of these molecules are large and besides their structures and properties it is important to investigate their interaction with DNA fragments (themselves large molecules). Ab initio calculations cannot always be applied to the whole system. Therefore, models are used and through a judicious choice of the entities investigated, the calculations can shed light on the problem and provide enough information to complement the experimental studies.

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