Cancer is the second leading cause of death worldwide. Majority of recent research efforts in the field aim to address why cancer resistance to therapy develops and how to overcome or prevent it. In line with this, novel anti-cancer compounds are desperately needed for chemoresistant cancer cells. Phytochemicals, in view of their pharmacological activities and capacity to target various molecular pathways, are of great interest in the development of therapeutics against cancer. Plant-derived-natural products have poor bioavailability which restricts their anti-tumor activity. Gallic acid (GA) is a phenolic acid exclusively found in natural sources such as gallnut, sumac, tea leaves, and oak bark. In this review, we report on the most recent research related to anti-tumor activities of GA in various cancers with a focus on its underlying molecular mechanisms and cellular pathwaysthat that lead to apoptosis and migration of cancer cells. GA down-regulates the expression of molecular pathways involved in cancer progression such as PI3K/Akt. The co-administration of GA with chemotherapeutic agents shows improvements in suppressing cancer malignancy. Various nano-vehicles such as organic- and inorganic nano-materials have been developed for targeted delivery of GA at the tumor site. Here, we suggest that nano-vehicles improve GA bioavailability and its ability for tumor suppression.

• MeSH
• Apoptosis drug effects   MeSH
• Antineoplastic Agents, Phytogenic administration & dosage   therapeutic use   MeSH
• Gallic Acid administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Neoplasms drug therapy   MeSH
• Nanoparticle Drug Delivery System * administration & dosage   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Gene therapy is an emerging and promising strategy in cancer therapy where small interfering RNA (siRNA) system has been deployed for down-regulation of targeted gene and subsequent inhibition in cancer progression; some issues with siRNA, however, linger namely, its off-targeting property and degradation by enzymes. Nanoparticles can be applied for the encapsulation of siRNA thus enhancing its efficacy in gene silencing where chitosan (CS), a linear alkaline polysaccharide derived from chitin, with superb properties such as biodegradability, biocompatibility, stability and solubility, can play a vital role. Herein, the potential of CS nanoparticles has been discussed for the delivery of siRNA in cancer therapy; proliferation, metastasis and chemoresistance are suppressed by siRNA-loaded CS nanoparticles, especially the usage of pH-sensitive CS nanoparticles. CS nanoparticles can provide a platform for the co-delivery of siRNA and anti-tumor agents with their enhanced stability via chemical modifications. As pre-clinical experiments are in agreement with potential of CS-based nanoparticles for siRNA delivery, and these carriers possess biocompatibiliy and are safe, further studies can focus on evaluating their utilization in cancer patients.

• MeSH
• Drug Resistance, Neoplasm drug effects   MeSH
• Chitosan chemistry   MeSH
• Humans MeSH
• RNA, Small Interfering chemistry   therapeutic use   MeSH
• Neoplasms drug therapy   pathology   therapy   MeSH
• Nanoparticles chemistry   MeSH
• Drug Carriers chemistry   MeSH
• Antineoplastic Agents chemistry   pharmacology   therapeutic use   MeSH
• Gene Silencing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• MeSH
• Autophagy * physiology   MeSH
• Autophagosomes MeSH
• Biomarkers MeSH
• Biological Assay standards   MeSH
• Humans MeSH
• Lysosomes MeSH
• Autophagy-Related Proteins metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Guideline MeSH

Tumor hypoxia is described as an oxygen deprivation in malignant tissue. The hypoxic condition is a consequence of an imbalance between rapidly proliferating cells and a vascularization that leads to lower oxygen levels in tumors. Hypoxia-inducible factor 1 (HIF-1) is an essential transcription factor contributing to the regulation of hypoxia-associated genes. Some of these genes modulate molecular cascades associated with the Warburg effect and its accompanying pathways and, therefore, represent promising targets for cancer treatment. Current progress in the development of therapeutic approaches brings several promising inhibitors of HIF-1. Flavonoids, widely occurring in various plants, exert a broad spectrum of beneficial effects on human health, and are potentially powerful therapeutic tools against cancer. Recent evidences identified numerous natural flavonoids and their derivatives as inhibitors of HIF-1, associated with the regulation of critical glycolytic components in cancer cells, including pyruvate kinase M2(PKM2), lactate dehydrogenase (LDHA), glucose transporters (GLUTs), hexokinase II (HKII), phosphofructokinase-1 (PFK-1), and pyruvate dehydrogenase kinase (PDK). Here, we discuss the results of most recent studies evaluating the impact of flavonoids on HIF-1 accompanied by the regulation of critical enzymes contributing to the Warburg phenotype. Besides, flavonoid effects on glucose metabolism via regulation of HIF-1 activity represent a promising avenue in cancer-related research. At the same time, only more-in depth investigations can further elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism.

• Publication type
• Journal Article MeSH
• Review MeSH