Progress in discovery and development of natural inhibitors of histone deacetylases (HDACs) as anti-cancer agents.

The study of epigenetic translational modifications had drawn great interest for the last few decades. These processes play a vital role in many diseases and cancer is one of them. Histone acetyltransferase (HAT) and histone deacetylases (HDACs) are key enzymes involved in the acetylation and deacetylation of histones and ultimately in post-translational modifications. Cancer frequently exhibits epigenetic changes, particularly disruption in the expression and activity of HDACs. It includes the capacity to regulate proliferative signalling, circumvent growth inhibitors, escape cell death, enable replicative immortality, promote angiogenesis, stimulate invasion and metastasis, prevent immunological destruction, and genomic instability. The majority of tumours develop and spread as a result of HDAC dysregulation. As a result, HDAC inhibitors (HDACis) were developed, and they today stand as a very promising therapeutic approach. One of the most well-known and efficient therapies for practically all cancer types is chemotherapy. However, the efficiency and safety of treatment are constrained by higher toxicity. The same has been observed with the synthetic HDACi. Natural products, owing to many advantages over synthetic compounds for cancer treatment have always been a choice for therapy. Hence, naturally available molecules are of particular interest for HDAC inhibition and HDAC has drawn the attention of the research fraternity due to their potential to offer a diverse array of chemical structures and bioactive compounds. This diversity opens up new avenues for exploring less toxic HDAC inhibitors to reduce side effects associated with conventional synthetic inhibitors. The review presents comprehensive details on natural product HDACi, their mechanism of action and their biological effects. Moreover, this review provides a brief discussion on the structure activity relationship of selected natural HDAC inhibitors and their analogues which can guide future research to discover selective, more potent HDACi with minimal toxicity.

Targeting the epigenetic reader "BET" as a therapeutic strategy for cancer.

Bromodomain and extraterminal (BET) proteins have the ability to bind to acetylated lysine residues present in both histones and non-histone proteins. This binding is facilitated by the presence of tandem bromodomains. The regulatory role of BET proteins extends to chromatin dynamics, cellular processes, and disease progression. The BET family comprises of BRD 2, 3, 4 and BRDT. The BET proteins are a class of epigenetic readers that regulate the transcriptional activity of a multitude of genes that are involved in the pathogenesis of cancer. Thus, targeting BET proteins has been identified as a potentially efficacious approach for the treatment of cancer. BET inhibitors (BETis) are known to interfere with the binding of BET proteins to acetylated lysine residues of chromatin, thereby leading to the suppression of transcription of several genes, including oncogenic transcription factors. Here in this review, we focus on role of Bromodomain and extra C-terminal (BET) proteins in cancer progression. Furthermore, numerous small-molecule inhibitors with pan-BET activity have been documented, with certain compounds currently undergoing clinical assessment. However, it is apparent that the clinical effectiveness of the present BET inhibitors is restricted, prompting the exploration of novel technologies to enhance their clinical outcomes and mitigate undesired adverse effects. Thus, strategies like development of selective BET-BD1, & BD2 inhibitors, dual and acting BET are also presented in this review and attempts to cover the chemistry needed for proper establishment of designed molecules into BRD have been made. Moreover, the review attempts to summarize the details of research till date and proposes a space for future development of BET inhibitor with diminished side effects. It can be concluded that discovery of isoform selective BET inhibitors can be a way forward in order to develop BET inhibitors with negligible side effects.

Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment.

Cancer is a leading cause of death globally, with limited treatment options and several limitations. Chemotherapeutic agents often result in toxicity which long-term conventional treatment. Phytochemicals are natural constituents that are more effective in treating various diseases with less toxicity than the chemotherapeutic agents providing alternative therapeutic approaches to minimize the resistance. These phytoconstituents act in several ways and deliver optimum effectiveness against cancer. Nevertheless, the effectiveness of phyto-formulations in the management of cancers may be constrained due to challenges related to inadequate solubility, bioavailability, and stability. Nanotechnology presents a promising avenue for transforming current cancer treatment methods through the incorporation of phytochemicals into nanosystems, which possess a range of advantageous characteristics such as biocompatibility, targeted and sustained release capabilities, and enhanced protective effects. This holds significant potential for future advancements in cancer management. Herein, this review aims to provide intensive literature on diverse nanocarriers, highlighting their applications as cargos for phytocompounds in cancer. Moreover, it offers an overview of the current advancements in the respective field, emphasizing the characteristics that contribute to favourable outcomes in both in vitro and in vivo settings. Lastly, clinical development and regulatory concerns are also discussed to check on the transformation of the concept as a promising strategy for combination therapy of phytochemicals and chemotherapeutics that could lead to cancer management in the future.

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce long-term antitumor memory, causing tumor regression, eradicate minimal residual illness, and prevent non-specific or unpleasant effects. These vaccines can assist in the elimination of cancer cells from various organs or organ systems in the body, with minimal risk of tumor recurrence or metastasis. Vaccines and antigens for anticancer therapy are discussed in this review, including current vaccine adjuvants and mechanisms of action for various types of vaccines, such as DNA- or mRNA-based cancer vaccines. Potential applications of these vaccines focusing on their clinical use for better therapeutic efficacy are also discussed along with the latest research available in this field.

Wound-Healing Effects of Curcumin and Its Nanoformulations: A Comprehensive Review.

Wound healing is an intricate process of tissue repair or remodeling that occurs in response to injury. Plants and plant-derived bioactive constituents are well explored in the treatment of various types of wounds. Curcumin is a natural polyphenolic substance that has been used since ancient times in Ayurveda for its healing properties, as it reduces inflammation and acts on several healing stages. Several research studies for curcumin delivery at the wound site reported the effectiveness of curcumin in eradicating reactive oxygen species and its ability to enhance the deposition of collagen, granulation tissue formation, and finally, expedite wound contraction. Curcumin has been widely investigated for its wound healing potential but its lower solubility and rapid metabolism, in addition to its shorter plasma half-life, have limited its applications in wound healing. As nanotechnology has proven to be an effective technique to accelerate wound healing by stimulating appropriate mobility through various healing phases, curcumin-loaded nanocarriers are used for targeted delivery at the wound sites. This review highlights the potential of curcumin and its nanoformulations, such as liposomes, nanoparticles, and nano-emulsions, etc. in wound healing. This paper emphasizes the numerous biomedical applications of curcumin which collectively prepare a base for its antibiofilm and wound-healing action.