To be Therapeutic.

Todays, nano-pharmaceutics is emerging as an important field of science to develop and improve efficacy of different drugs. Although nutraceuticals are currently being utilized in the prevention and treatment of various chronic diseases such as cancers, a number of them have displayed issues associated with their solubility, bioavailability, and bio-degradability. In the present review, we focus on curcumin, an important and widely used polyphenol, with diverse pharmacological activities such as anti-inflammatory, anti-carcinogenic, anti-viral, etc. Notwithstanding, it also exhibits poor solubility and bioavailability that may compromise its clinical application to a great extent. Therefore, the manipulation and encapsulation of curcumin into a nanocarrier formulation can overcome these major drawbacks and potentially may lead to a far superior therapeutic efficacy. Among different types of nanocarriers, biological and biopolymer carriers have attracted a significant attention due to their pleiotropic features. Thus, in the present review, the potential protective and therapeutic applications of curcumin, as well as different types of bio-nanocarriers, which can be used to deliver curcumin effectively to the different target sites will be discussed.

https://www.mdpi.com/1420-3049/25/3/689/pdf

Curcumin Delivery Mediated by Bio-Based Nanoparticles: A Review.

The tumour microenvironment (TME) constitutes the area surrounding the tumour during its development and has been demonstrated to play roles in cancer-related diseases through crosstalk with tumour cells. Circular RNAs (circRNAs) are a subpopulation of endogenous noncoding RNAs (ncRNAs) that are ubiquitously expressed in eukaryotes and have multiple biological functions in the regulation of cancer onset and progression. An increasing number of studies have shown that circRNAs participate in the multifaceted biological regulation of the TME. However, details on the mechanisms involved have remained elusive until now. In this review, we analyse the effects of circRNAs on the TME from various perspectives, including immune surveillance, angiogenesis, hypoxia, matrix remodelling, exo-circRNAs and chemoradiation resistance. Currently, the enormous potential for circRNA use in targeted therapy and as noninvasive biomarkers have drawn our attention. We emphasize the prospect of targeting circRNAs as an essential strategy to regulate TME, overcome cancer resistance and improve therapeutic outcomes.

/pdf/roles-of-circrnas-in-the-tumour-microenvironment-3860pz1f4f.pdf

Roles of circRNAs in the tumour microenvironment

Cancer represents a serious global health problem, and its incidence and mortality are rapidly growing worldwide. One of the main causes of the failure of an anticancer treatment is the development of drug resistance by cancer cells. Therefore, it is necessary to develop new drugs characterized by better pharmacological and toxicological profiles. Natural compounds can represent an optimal collection of bioactive molecules. Many natural compounds have been proven to possess anticancer effects in different types of tumors, but often the molecular mechanisms associated with their cytotoxicity are not completely understood. The endoplasmic reticulum (ER) is an organelle involved in multiple cellular processes. Alteration of ER homeostasis and its appropriate functioning originates a cascade of signaling events known as ER stress response or unfolded protein response (UPR). The UPR pathways involve three different sensors (protein kinase RNA(PKR)-like ER kinase (PERK), inositol requiring enzyme1α (IRE1) and activating transcription factor 6 (ATF6)) residing on the ER membranes. Although the main purpose of UPR is to restore this organelle's homeostasis, a persistent UPR can trigger cell death pathways such as apoptosis. There is a growing body of evidence showing that ER stress may play a role in the cytotoxicity of many natural compounds. In this review we present an overview of different plant-derived natural compounds, such as curcumin, resveratrol, green tea polyphenols, tocotrienols, and garcinia derivates, that exert their anticancer activity via ER stress modulation in different human cancers.

https://www.mdpi.com/1422-0067/20/4/961/pdf

Role of Endoplasmic Reticulum Stress in the Anticancer Activity of Natural Compounds.

Paeonol (Pae), a phenolic acid compound isolated from the Moutan Cortex, was previously demonstrated to exert multiple anticancer effects. The rational control of autophagy has been considered a potential treatment strategy for epithelial ovarian cancer. However, whether Pae induces autophagy and the relationship between its antitumour activities and autophagy in epithelial ovarian cancer are still unclear. In this study, we found that Pae induced not only antiproliferation activity and apoptosis but also autophagy, and complete autophagic flux was observed in A2780 and SKOV3 cells. In addition, combination treatment with Pae and an autophagy inhibitor (3-methyladenine and hydroxychloroquine) showed significant synergetic effects on inhibiting cell viability and promoting apoptosis in vitro and in the A2780 xenograft model, without severe side effects, which was often had by cisplatin. These results indicate that autophagy induced by Pae has a cytoprotective role in both A2780 and SKOV3 cells. Mechanistically, we found that Pae inhibited the protein kinase B(Akt)/mammalian target of rapamycin (mTOR) pathway. Furthermore, when combined with the inhibitors MK2206 and rapamycin to inhibit Akt and mTOR kinase activity, Pae-induced autophagy was increased. Taken together, our results demonstrate that Pae induced cytoprotective autophagy by inhibiting the Akt/mTOR pathway in ovarian cancer cells. Thus, the strategy of combining Pae with an autophagy inhibitor to block Akt/mTOR-dependent autophagy could enhance the antitumour activity of Pae and warrants further application for the treatment of ovarian cancer.

/pdf/paeonol-induces-cytoprotective-autophagy-via-blocking-the-2axn1881am.pdf

Paeonol induces cytoprotective autophagy via blocking the Akt/mTOR pathway in ovarian cancer cells.

Cancer is the second leading cause of death in the world. Chemotherapy and radiotherapy are the common cancer treatments. However, the development of adverse effects resulting from chemotherapy and radiotherapy hinders the clinical use, and negatively reduces the quality of life in cancer patients. Natural products including crude extracts, bioactive components-enriched fractions and pure compounds prepared from herbs as well as herbal formulas have been proved to prevent and treat cancer. Of significant interest, some natural products can reduce chemotherapy and radiotherapy-induced oral mucositis, gastrointestinal toxicity, hepatotoxicity, nephrotoxicity, hematopoietic system injury, cardiotoxicity, and neurotoxicity. This review focuses in detail on the effectiveness of these natural products, and describes the possible mechanisms of the actions in reducing chemotherapy and radiotherapy-induced side effects. Recent advances in the efficacy of natural dietary supplements to counteract these side effects are highlighted. In addition, we draw particular attention to gut microbiotan in the context of prebiotic potential of natural products for the protection against cancer therapy-induced toxicities. We conclude that some natural products are potential therapeutic perspective for the prevention and treatment of chemotherapy and radiotherapy-induced side effects. Further studies are required to validate the efficacy of natural products in cancer patients, and elucidate potential underlying mechanisms.

/pdf/natural-product-interventions-for-chemotherapy-and-553ddawoje.pdf

Qing-Yu Zhang

Papers

Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects.