-
1.
A Compressive Review about Taxol®: History and Future Challenges.
Gallego-Jara, J, Lozano-Terol, G, Sola-Martínez, RA, Cánovas-Díaz, M, de Diego Puente, T
Molecules (Basel, Switzerland). 2020;(24)
Abstract
Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent.
-
2.
Flavonoids as Anticancer Agents.
Kopustinskiene, DM, Jakstas, V, Savickas, A, Bernatoniene, J
Nutrients. 2020;(2)
Abstract
Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis-they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.
-
3.
Annexin A1 involved in the regulation of inflammation and cell signaling pathways.
Han, PF, Che, XD, Li, HZ, Gao, YY, Wei, XC, Li, PC
Chinese journal of traumatology = Zhonghua chuang shang za zhi. 2020;(2):96-101
Abstract
With the deepening of research, proteomics has developed into a science covering the study of all the structural and functional characteristics of proteins and the dynamic change rules. The essence of various biological activities is revealed from the perspectives of the biological structure, functional activity and corresponding regulatory mechanism of proteins by proteomics. Among them, phospholipid-binding protein is one of the hotspots of proteomics, especially annexin A1, which is widely present in various tissues and cells of the body. It has the capability of binding to phospholipid membranes reversibly in a calcium ion dependent manner. In order to provide possible research ideas for researchers, who are interested in this protein, the biological effects of annexin A1, such as inflammatory regulation, cell signal transduction, cell proliferation, differentiation and apoptosis are described in this paper.
-
4.
Anti-cancer effects of Polyphyllin I: An update in 5 years.
Tian, Y, Gong, GY, Ma, LL, Wang, ZQ, Song, D, Fang, MY
Chemico-biological interactions. 2020;:108936
Abstract
Chong-lou, the rhizome of Paris polyphylla, has been used in herbal regimes to treat parotitis, mastitis and certain malignant tumors for thousands of years in traditional medicine. Polyphyllin I (PPI) is the main bioactive component in Paris polyphylla. Recent studies of PPI in various types of cancers have shown that PPI may exert a broad spectrum of anti-tumor effects, including inducing cell cycle arrest, inducing cell apoptosis, inducing autophagy, anti-angiogenesis, sensitizing tumors to chemotherapy, and participating in the modulation of inflammatory and immune response. Along with the growing research interest in PPI as well as accumulation of experimental evidences, this review periodically summarized the recent advances in regard to PPI's anti-tumor propensities in various cancers and the underlying mechanisms for future prospective research.
-
5.
Inositol Hexaphosphate (IP6) and Colon Cancer: From Concepts and First Experiments to Clinical Application.
Vucenik, I, Druzijanic, A, Druzijanic, N
Molecules (Basel, Switzerland). 2020;(24)
Abstract
Multiple human health-beneficial effects have been related to highly phosphorylated inositol hexaphosphate (IP6). This naturally occurring carbohydrate and its parent compound, myo-inositol (Ins), are abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate important cellular functions. However, the striking and broad-spectrum anticancer activity of IP6, consistently demonstrated in different experimental models, has been in a spotlight of the scientific community dealing with the nutrition and cancer during the last several decades. First experiments were performed in colon cancer 30 years ago. Since then, it has been shown that IP6 reduces cell proliferation, induces apoptosis and differentiation of malignant cells with reversion to normal phenotype, affecting several critical molecular targets. Enhanced immunity and antioxidant properties also contribute to the tumor cell destruction. Although Ins possesses a modest anticancer potential, the best anticancer results were obtained from the combination of IP6 + Ins. Here we review the first experimental steps in colon cancer, when concepts and hypotheses were put together almost without real knowledge and present clinical studies, that were initiated in colon cancer patients. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves quality of life in cancer patients. Emerging clinical and still vast amount of experimental data suggest its role either as an adjuvant or as an "alternative" to current chemotherapy for cancer.
-
6.
Curcumin Sensitizes Cancers Towards TRAIL-induced Apoptosis via Extrinsic and Intrinsic Apoptotic Pathways.
Ngai, SC
Current drug targets. 2020;(9):849-854
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a natural protein expressed in a wide range of tissues in our body. It is a promising anti-cancer agent due to its selective killing of cancer cells, rendering normal cells unharmed. However, resistance occurs either intrinsically or develops over the course of TRAIL treatment. In view of its specificity to cancer cells, there is a pushing need to overcome TRAIL resistance. Curcumin (Cur), a natural active constituent of turmeric, has been evidenced to have anti-cancer properties. However, it is limited by its sparing solubility and low bioavailability. Combinational therapy is one of the most frequently used strategies to overcome these limitations, which has been proved to be more effective than monotherapy by achieving synergistic effects and reducing toxicity. This review aims to discuss TRAIL and its underlying apoptotic mechanisms, the combinational treatment of Cur and TRAIL in view of their respective limitations, and the underlying apoptotic mechanisms activated by the sensitization of cancers by Cur towards TRAIL-induced apoptosis. Finally, this review discusses the research gap and the author's insight into this research area in bridging the research gap from bench to bedside.
-
7.
Natural Agents Targeting Mitochondria in Cancer.
Mani, S, Swargiary, G, Singh, KK
International journal of molecular sciences. 2020;(19)
Abstract
Mitochondria are the key energy provider to highly proliferating cancer cells, and are subsequently considered one of the critical targets in cancer therapeutics. Several compounds have been studied for their mitochondria-targeting ability in cancer cells. These studies' outcomes have led to the invention of "mitocans", a category of drug known to precisely target the cancer cells' mitochondria. Based upon their mode of action, mitocans have been divided into eight classes. To date, different synthetic compounds have been suggested to be potential mitocans, but unfortunately, they are observed to exert adverse effects. Many studies have been published justifying the medicinal significance of large numbers of natural agents for their mitochondria-targeting ability and anticancer activities with minimal or no side effects. However, these natural agents have never been critically analyzed for their mitochondria-targeting activity. This review aims to evaluate the various natural agents affecting mitochondria and categorize them in different classes. Henceforth, our study may further support the potential mitocan behavior of various natural agents and highlight their significance in formulating novel potential anticancer therapeutics.
-
8.
Apoptosis in Autoimmunological Diseases, with Particular Consideration of Molecular Aspects of Psoriasis.
Krawczyk, A, Miśkiewicz, J, Strzelec, K, Wcisło-Dziadecka, D, Strzalka-Mrozik, B
Medical science monitor : international medical journal of experimental and clinical research. 2020;:e922035
Abstract
Apoptosis is a natural physiological process involving programmed cell death. Thanks to this process, it is possible to maintain the homeostasis of the body and the immune system. Dysfunctions of this mechanism lead to development of autoimmune diseases such as psoriasis; these diseases are chronic and treatment is extremely difficult. In psoriasis (a skin disease), apoptosis disorders are manifested by keratinocyte proliferation dysfunction. Autoimmune diseases coexisting with psoriasis include multiple sclerosis, autoimmune thyroid disease, and diabetes, but the common pathogenesis of these diseases is not fully understood. Given the heterogenous nature and chronic and recurrent course of psoriasis, the selection of an effective therapeutic strategy is still a problem. This literature review was focused on the process of apoptosis as a factor in the development of autoimmune diseases, with particular emphasis on psoriasis. The work also includes a review of therapeutic methods of psoriasis based on the latest literature.
-
9.
Curcumin, a Multifaceted Hormetic Agent, Mediates an Intricate Crosstalk between Mitochondrial Turnover, Autophagy, and Apoptosis.
Rainey, NE, Moustapha, A, Petit, PX
Oxidative medicine and cellular longevity. 2020;:3656419
Abstract
Curcumin has extensive therapeutic potential because of its antioxidant, anti-inflammatory, and antiproliferative properties. Multiple preclinical studies in vitro and in vivo have proven curcumin to be effective against various cancers. These potent effects are driven by curcumin's ability to induce G2/M cell cycle arrest, induce autophagy, activate apoptosis, disrupt molecular signaling, inhibit invasion and metastasis, and increase the efficacy of current chemotherapeutics. Here, we focus on the hormetic behavior of curcumin. Frequently, low doses of natural chemical products activate an adaptive stress response, whereas high doses activate acute responses like autophagy and cell death. This phenomenon is often referred to as hormesis. Curcumin causes cell death and primarily initiates an autophagic step (mitophagy). At higher doses, cells undergo mitochondrial destabilization due to calcium release from the endoplasmic reticulum, and die. Herein, we address the complex crosstalk that involves mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy, and cell death.
-
10.
Molecular mechanisms of natural compounds in cell death induction and sensitization to chemotherapeutic drugs in lung cancer.
Wattanathamsan, O, Hayakawa, Y, Pongrakhananon, V
Phytotherapy research : PTR. 2019;(10):2531-2547
Abstract
Cancer remains one of the leading causes of death worldwide, especially lung cancer. Chemotherapeutic drugs are commonly used for lung cancer treatment; nonetheless, undesirable side effects and drug resistance remain major challenges for therapeutic success. Therefore, harmless and effective treatments against lung cancer are urgently required. The use of natural phytochemical products, in single or combinatorial therapy, is an emerging strategy for prevention and cure of cancer because of the various remarkable anticancer properties of these compounds. Cell death, which primarily occurs via apoptosis and nonapoptotic mechanisms (necrosis, autophagy, and cellular senescence), is one of the antineoplastic effects of natural compounds. In this review, we highlight representative plant-derived compounds with cancer chemopreventive and sensitizing effects in combination with chemotherapeutic drugs with various cell death-inducing mechanisms. Relevant molecular mechanisms implicated in the pharmacological effects of these natural compounds are discussed. Overall, this review provides a reference and new perspective for application of phytochemical agents as potential anti-lung cancer drugs for further cancer drug research and development.