scholarly journals Cancer Chemoprevention: A Strategic Approach Using Phytochemicals

2022 ◽  
Vol 12 ◽  
Author(s):  
Mohan Shankar G. ◽  
Mundanattu Swetha ◽  
C K Keerthana ◽  
Tennyson P Rayginia ◽  
Ruby John Anto

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associated with conventional chemotherapies decrease the success rates of the existent chemotherapeutic regimen, which warrants the need for an efficient and safer alternative therapeutic approach. In this scenario, chemopreventive agents have been proven to be successful in protecting the high-risk populations from cancer, which further validates chemoprevention strategy as rational and promising. Clinical studies have shown the effectiveness of this approach in managing cancers of different origins. Phytochemicals, which constitute an appreciable proportion of currently used chemotherapeutic drugs, have been tested for their chemopreventive efficacy. This review primarily aims to highlight the efficacy of phytochemicals, currently being investigated globally as chemopreventives. The clinical relevance of chemoprevention, with special emphasis on the phytochemicals, curcumin, resveratrol, tryptanthrin, kaempferol, gingerol, emodin, quercetin genistein and epigallocatechingallate, which are potential candidates due to their ability to regulate multiple survival pathways without inducing toxicity, forms the crux of this review. The majority of these phytochemicals are polyphenols and flavanoids. We have analyzed how the key molecular targets of these chemopreventives potentially counteract the key drivers of chemoresistance, causing minimum toxicity to the body. An overview of the underlying mechanism of action of these phytochemicals in regulating the key players of cancer progression and tumor suppression is discussed in this review. A summary of the clinical trials on the important phytochemicals that emerge as chemopreventives is also incorporated. We elaborate on the pre-clinical and clinical observations, pharmacokinetics, mechanism of action, and molecular targets of some of these natural products. To summarize, the scope of this review comprises of the current status, limitations, and future directions of cancer chemoprevention, emphasizing the potency of phytochemicals as effective chemopreventives.

2019 ◽  
Vol 20 (20) ◽  
pp. 4981 ◽  
Author(s):  
Alok Ranjan ◽  
Sharavan Ramachandran ◽  
Nehal Gupta ◽  
Itishree Kaushik ◽  
Stephen Wright ◽  
...  

The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.


2021 ◽  
Vol 15 (2) ◽  
pp. 112-119
Author(s):  
L. I. Alekseeva ◽  
A. M. Lila

The article highlights the current status of symptomatic slow-acting drugs (SYSADOA) in osteoarthritis (OA). Mechanism of action, clinical studies data on the effectiveness of glucosamine (GA) and chondroitin sulfate (CS) and their combinations in OA, their positive symptomatic and structural-modifying effects, are described. The article provides the latest recommendations for the OA treatment with these two drugs and presents an argument for the combination therapy with both drugs as a background therapy in the earliest stages of OA. It is indicated that such therapy should be long-term due to its high safety and possible reduction of cardiovascular accidents risk as well. It is noted that therapeutic doses of CS and GA are ≥1500 and ≥800 mg per day, respectively, and encapsulated forms of SYSADOAs have advantages due to their pharmacokinetic features.


2014 ◽  
Vol 7 ◽  
pp. CGM.S11288 ◽  
Author(s):  
Kristin R. Landis-Piwowar ◽  
Neena R. Iyer

The aim of cancer chemoprevention is disruption or delay of the molecular pathways that lead to carcinogenesis. Chemopreventive blocking and/or suppressing agents disrupt the molecular mechanisms that drive carcinogenesis such as DNA damage by reactive oxygen species, increased signal transduction to NF-κB, epigenomic deregulation, and the epithelial mesenchymal transition that leads to metastatic progression. Numerous dietary phytochemicals have been observed to inhibit the initiation phase of carcinogenesis, and therefore are useful in primary chemoprevention. Moreover, phytochemicals are capable of interfering with the molecular mechanisms of metastasis. Likewise, numerous synthetic compounds are relevant and clinically viable as chemopreventive agents during the fundamental stages of carcinogenesis. While molecularly targeted anti-cancer therapies are in constant stages of development, superior patient outcomes are observed if carcinogenic processes are prevented altogether. This article reviews the role of chemopreventive compounds in inhibition of cancer initiation and their ability to reduce cancer progression.


Author(s):  
Kinesh V P ◽  
Neelam D P ◽  
Punit B ◽  
Bhavesh S.B ◽  
Pragna K. S

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.


2018 ◽  
Vol 24 (14) ◽  
pp. 1533-1550 ◽  
Author(s):  
Jong-Eun Kim ◽  
Ki Won Lee

Skin is a protective organ and the largest of the human body. Due to its pivotal role in aesthetic appearance, skin health has a significant impact on quality of life. Chronic inflammation of the skin often marks the beginning of various skin diseases. Immune-mediated responses serve to protect the body from external insults and require succinct control, and can lead to ongoing cellular damage and various skin conditions if left unchecked. Studies have shown that phytochemicals can alter processes involved in skin inflammation and alleviate the effects of aging, cancer, atopic dermatitis, psoriasis, and vitiligo. Direct molecular targets of some phytochemicals have been identified and their precise mechanisms of action investigated. In this review, we summarize recent findings on the effects of phytochemicals on skin inflammation and the mechanisms of action involved.


2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.


Author(s):  
Robert Laumbach ◽  
Michael Gochfeld

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.


2020 ◽  
Vol 11 ◽  
pp. 215145932098036
Author(s):  
David W. Barton ◽  
C. Taylor Smith ◽  
Amit S. Piple ◽  
Sterling A. Moskal ◽  
Jonathan J. Carmouche

Introduction: Osteoporosis is often not clinically recognized until after a fracture occurs. Individuals who have 1 fracture are at increased risk of future fractures. Prompt initiation of osteoporosis treatment following fracture is critical to reducing the rate of future fractures. Antiresorptives are the most widely used class of medications for the prevention and treatment of osteoporosis. Many providers are hesitant to initiate antiresorptives in the acute post-fracture period. Concerns include interference with bone remodeling necessary for successful fracture healing, which would cause increased rates of non-union, malunion, and refracture. While such concerns should not extend to anabolic medications, physicians may also hesitate to initiate anabolic osteoporosis therapies due to high cost and/or lack of familiarity. This article aims to briefly review the available data and present a digestible narrative summary to familiarize practicing orthopaedic surgeons with the essential details of the published research on this topic. Results: The results of 20 clinical studies and key pre-clinical studies related to the effect of anti-resorptive medications for osteoporosis on fracture healing are summarized in the body of this narrative review. Discussion & Conclusions: While few level I studies have examined the impact of timing of initiation of osteoporosis medications in the acute post-fracture period, the few that have been published do not support these concerns. Specifically, data from level I clinical trials indicate that initiating bisphosphonates as early as 2 weeks post-fracture does not increase rates of non-union or malunion. By reviewing the available data, we hope to give clinicians the confidence to initiate osteoporosis treatment promptly post-fracture.


RSC Advances ◽  
2021 ◽  
Vol 11 (19) ◽  
pp. 11610-11626
Author(s):  
Reham S. Ibrahim ◽  
Alaa A. El-Banna

Multi-level mechanism of action of propolis constituents in cancer treatment using an integrated approach of network pharmacology-based analysis, molecular docking and in vitro cytotoxicity testing.


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