Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals.

Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed.

Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention.

Cancer remains to be the second highest cause of mortality in our society, falling just short of heart disease. Despite major advancement in cancer therapy over the past decade, momentum has been gaining for an alternative approach of using naturally-occurring and dietary agents for cancer prevention and management. Research on pomegranate (Punica granatum L.), a fruit of the Punicaceae family, has shown enormous potential for cancer prevention and intervention. In addition to a rich source of polyphenols, including flavonoids and ellagitannins, in its juice, pomegranate also houses hundreds of other phytochemicals in its pericarp, seed, flower, bark, flowers and leaves. These phytochemicals provide powerful antiproliferative, anti-inflammatory, antioxidant, anti-invasive, antimigratory, anti-angiogenic and anti-metastatic effects without significant toxicity. This makes the use of its various extracts a very attractive strategy to our current battle against cancer. This review article presents a systematic, comprehensive and critical review of research on pomegranate-derived products in both cancer prevention and intervention. It discusses the chemical constituents of pomegranate, the results of both preclinical (in vitro, ex vivo and in vivo) and clinical studies on the anticancer effect of pomegranate phytochemicals and molecular targets in numerous types of cancers, such as breast, gastrointestinal tract (oral, colon, liver and pancreas), gynecological (uterine and ovarian), hematological (lymphoma, leukemia and myeloma), lung, neurological (glioma), urogenital (bladder and prostate), bioavailability, pharmacokinetics and safety of pomegranate constituents. In order to guide the direction of future research, we have also included current limitations and challenges in the field and our post analysis recommendation.

Mango (Mangifera indica L.): a magnificent plant with cancer preventive and anticancer therapeutic potential.

Mangifera indica L. (mango), a long-living evergreen plant belonging to the Anacardiaceae family, has been cultivated for thousands of years in the Indian subcontinent for its excellent fruits which represent a rich source of fiber, vitamin A and C, essential amino acids, and a plethora of phytochemicals. M. indica is extensively used in various traditional systems of medicine to prevent and treat several diseases. The health-promoting and disease-preventing effects of M. indica are attributed to a number of bioactive phytochemicals, including polyphenols, terpenoids, carotenoid and phytosterols, found in the leaf, bark, edible flesh, peel, and seed. M. indica has been shown to exhibit various biological and pharmacological activities, such as antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antidiabetic, antiobesity, and anticancer effects. There are a few studies conducted that have indicated the nontoxic nature of mango constituents. However, while there are numerous individual studies investigating anticancer effects of various constituents from the mango tree, an up-to-date, comprehensive and critical review of available research data has not been performed according to our knowledge. The purpose of this review is to present a comprehensive and critical evaluation of cancer preventive and anticancer therapeutic potential of M. indica and its phytochemicals with special focus on the cellular and molecular mechanisms of action. The bioavailability, pharmacokinetics, and safety profile of individual phytocomponents of M. indica as well as current limitations, challenges, and future directions of research have also been discussed.

Anticancer potential of garlic and its bioactive constituents: A systematic and comprehensive review.

Vegetables of the Allium genus, such as garlic (Allium sativum L.), onions, shallots, leaks, and chives, have been used for many years for food consumption and for medicinal purposes. Historical medical texts have indicated the therapeutic applications of garlic as an antitumor, laxative, diuretic, antibacterial and antifungal agent. Specifically, garlic's antitumor abilities have been traced back 3500 years as a chemotherapeutic agent used in Egypt. Other beneficial effects of garlic consumption include lowering blood pressure, blood cholesterol, sugar and lipids. The processing and aging of garlic result in the production of non-toxic organosulfur by-products. These sulfur-containing compounds, such as allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, alliin, S-allylcysteine, and S-allylmercaptocysteine, impact various stages of carcinogenesis. The anticancer mechanisms of action of these garlic-derived phytochemicals include altering mitochondrial permeability, inhibiting angiogenesis, enhancing antioxidative and proapoptotic properties, and regulating cell proliferation. All these effects of garlic's sulfur-compounds have been demonstrated in various human cancers. The intent of this literature research is to explore the potential of garlic-derived products and bioactive organosulfur compounds as cancer chemopreventive and chemotherapeutic agents. This investigation employs criteria for systematic review and critically analyzes published in vitro, in vivo and clinical studies. Concerns and limitations that have arisen in past studies regarding standards of measurement, bioavailability, and method of delivery are addressed. Overall, it is hoped that through this systematic and comprehensive review, future researchers can be acquainted with the updated data assembled on anticancer properties of garlic and its phytoconstituents.

Targeting the JAK/STAT Signaling Pathway Using Phytocompounds for Cancer Prevention and Therapy.

Cancer is a prevalent cause of mortality around the world. Aberrated activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway promotes tumorigenesis. Natural agents, including phytochemicals, exhibit potent anticancer activities via various mechanisms. However, the therapeutic potency of phytoconstituents as inhibitors of JAK/STAT signaling against cancer has only come into focus in recent days. The current review highlights phytochemicals that can suppress the JAK/STAT pathway in order to impede cancer cell growth. Various databases, such as PubMed, ScienceDirect, Web of Science, SpringerLink, Scopus, and Google Scholar, were searched using relevant keywords. Once the authors were in agreement regarding the suitability of a study, a full-length form of the relevant article was obtained, and the information was gathered and cited. All the complete articles that were incorporated after the literature collection rejection criteria were applied were perused in-depth and material was extracted based on the importance, relevance, and advancement of the apprehending of the JAK/STAT pathway and their relation to phytochemicals. Based on the critical and comprehensive analysis of literature presented in this review, phytochemicals from diverse plant origins exert therapeutic and cancer preventive effects, at least in part, through regulation of the JAK/STAT pathway. Nevertheless, more preclinical and clinical research is necessary to completely comprehend the capability of modulating JAK/STAT signaling to achieve efficient cancer control and treatment.

Antiangiogenic Effects of Coumarins against Cancer: From Chemistry to Medicine.

Angiogenesis, the process of formation and recruitment of new blood vessels from pre-existing vessels, plays an important role in the development of cancer. Therefore, the use of antiangiogenic agents is one of the most critical strategies for the treatment of cancer. In addition, the complexity of cancer pathogenicity raises the need for multi-targeting agents. Coumarins are multi-targeting natural agents belonging to the class of benzopyrones. Coumarins have several biological and pharmacological effects, including antimicrobial, antioxidant, anti-inflammation, anticoagulant, anxiolytic, analgesic, and anticancer properties. Several reports have shown that the anticancer effect of coumarins and their derivatives are mediated through targeting angiogenesis by modulating the functions of vascular endothelial growth factor as well as vascular endothelial growth factor receptor 2, which are involved in cancer pathogenesis. In the present review, we focus on the antiangiogenic effects of coumarins and related structure-activity relationships with particular emphasis on cancer.

Targeting Inflammation by Flavonoids: Novel Therapeutic Strategy for Metabolic Disorders.

A balanced metabolic profile is essential for normal human physiological activities. Disproportions in nutrition give rise to imbalances in metabolism that are associated with aberrant immune function and an elevated risk for inflammatory-associated disorders. Inflammation is a complex process, and numerous mediators affect inflammation-mediated disorders. The available clinical modalities do not effectively address the underlying diseases but rather relieve the symptoms. Therefore, novel targeted agents have the potential to normalize the metabolic system and, thus, provide meaningful therapy to the underlying disorder. In this connection, polyphenols, the well-known and extensively studied phytochemical moieties, were evaluated for their effective role in the restoration of metabolism via various mechanistic signaling pathways. The various flavonoids that we observed in this comprehensive review interfere with the metabolic events that induce inflammation. The mechanisms via which the polyphenols, in particular flavonoids, act provide a promising treatment option for inflammatory disorders. However, detailed clinical studies of such molecules are required to decide their clinical fate.