Design, synthesis and mechanistic studies of novel arylformylhydrazone butylphenyltin complexes as potential anticancer agents.

Many diorganotin complexes with various alkyl groups exhibit excellent in vitro anticancer activity. However, most diorganotin is the same alkyl group, and the asymmetric alkyl R group has been rarely reported. Hence, in this paper, twenty butylphenyl mixed dialkyltin arylformylhydrazone complexes have been synthesized by microwave "one-pot" reaction with arylformylhydrazine, substituted α-keto acid or its sodium salt and butylphenyltin dichloride. The crystal structures of nine complexes were determined, indicating that the complexes C1, C2, C11, C12, and C16 âˆ¼ C19 possessed a central symmetric structure of a dinuclear Sn2O2 tetrahedral ring; while the complex C9 is a trinuclear tin-oxygen cluster with a 6-membered ring encased in a 12-membered macrocyclic structure. The inhibiting activity of complexes was tested against the human cell lines NCI-H460, MCF-7, HepG2, Huh-7 and HL-7702. Complex C2 demonstrated the optimal inhibitory effect on HepG2 cells, with an IC50 value of 0.82 ± 0.03 µM. Cellular biology experiments revealed that complex C2 could induce apoptosis and G2/M phase cell cycle arrest in HepG2 and Huh-7 cells. The complex also caused the collapse of the mitochondrial membrane potential and increased intracellular reactive oxygen species in HepG2 and Huh-7 cells. Western blot analysis further clarified that complex C2 could induce cell apoptosis through the mitochondrial pathway along with the release of reactive oxygen species.

Withanolides: Promising candidates for cancer therapy.

Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted.

Anticancer and chemopreventive potential of Morinda citrifolia L. bioactive compounds: A comprehensive update.

Morinda citrifolia L., commonly known as Noni, has a longstanding history in traditional medicine for treating various diseases. Recently, there has been an increased focus on exploring Noni extracts and phytoconstituents, particularly for their effectiveness against cancers such as lung, esophageal, liver, and breast cancer, and their potential in cancer chemoprevention. This study aims to provide a comprehensive review of in vitro and in vivo studies assessing Noni's impact on cancer, alongside an exploration of its bioactive compounds. A systematic review was conducted, encompassing a wide range of scientific databases to gather pertinent literature. This review focused on in vitro and in vivo studies, as well as clinical trials that explore the effects of Noni fruit and its phytoconstituents-including anthraquinones, flavonoids, sugar derivatives, and neolignans-on cancer. The search was meticulously structured around specific keywords and criteria to ensure a thorough analysis. The compiled studies highlight Noni's multifaceted role in cancer therapy, showcasing its various bioactive components and their modes of action. This includes mechanisms such as apoptosis induction, cell cycle arrest, antiangiogenesis, and immune system modulation, demonstrating significant anticancer and chemopreventive potential. The findings reinforce Noni's potential as a safe and effective option in cancer prevention and treatment. This review underscores the need for further research into Noni's anticancer properties, with the hope of stimulating additional studies and clinical trials to validate and expand upon these promising findings.

Anticancer Potential of ß-Carboline Alkaloids: An Updated Mechanistic Overview.

his comprehensive review is designed to evaluate the anticancer properties of ß-carbolines derived from medicinal plants, with the ultimate goal of assessing their suitability and potential in cancer treatment, management, and prevention. An exhaustive literature survey was conducted on a wide array of ß-carbolines including, but not limited to, harmaline, harmine, harmicine, harman, harmol, harmalol, pinoline, tetrahydroharmine, tryptoline, cordysinin C, cordysinin D, norharmane, and perlolyrine. Various analytical techniques were employed to identify and screen these compounds, followed by a detailed analysis of their anticancer mechanisms. Natural ß-carbolines such as harmaline and harmine have shown promising inhibitory effects on the growth of cancer cells, as evidenced by multiple in vitro and in vivo studies. Synthetically derived ß-carbolines also displayed noteworthy anticancer, neuroprotective, and cognitive-enhancing effects. The current body of research emphasizes the potential of ß-carbolines as a unique source of bioactive compounds for cancer treatment. The diverse range of ß-carbolines derived from medicinal plants can offer valuable insights into the development of new therapeutic strategies for cancer management and prevention.

Anticancer Mechanisms and Potential Anticancer Applications of Antimicrobial Peptides and Their Nano Agents.

Traditional chemotherapy is one of the main methods of cancer treatment, which is largely limited by severe side effects and frequent development of multi-drug resistance by cancer cells. Antimicrobial peptides (AMPs) with high efficiency and low toxicity, as one of the most promising new drugs to replace chemoradiotherapy, have become a current research hotspot, attracting the attention of worldwide researchers. AMPs are natural-source small peptides from the innate immune system, and certain AMPs can selectively kill a broad spectrum of cancer cells while exhibiting less damage to normal cells. Although it involves intracellular mechanisms, AMPs exert their anti-cancer effects mainly through membrane destruction effect; thus, AMPs also hold unique advantages in fighting drug-resistant cancer cells. However, the poor stability and hemolytic toxicity of peptides limit their clinical application. Fortunately, functionalized nanoparticles have many possibilities in overcoming the shortcomings of AMPs, which provides a huge prospect for better application of AMPs. In this paper, we briefly introduce the characteristics and different sources of AMPs, review and summarize the mechanisms of action and the research status of AMPs used as an anticancer therapy, and finally focus on the further use of AMPs nano agents in the anti-cancer direction.

Thymol as adjuvant in oncology: molecular mechanisms, therapeutic potentials, and prospects for integration in cancer management.

Cancer remains a global health challenge, prompting a search for effective treatments with fewer side effects. Thymol, a natural monoterpenoid phenol derived primarily from thyme (Thymus vulgaris) and other plants in the Lamiaceae family, is known for its diverse biological activities. It emerges as a promising candidate in cancer prevention and therapy. This study aims to consolidate current research on thymol's anticancer effects, elucidating its mechanisms and potential to enhance standard chemotherapy, and to identify gaps for future research. A comprehensive review was conducted using databases like PubMed/MedLine, Google Scholar, and ScienceDirect, focusing on studies from the last 6 years. All cancer types were included, assessing thymol's impact in both cell-based (in vitro) and animal (in vivo) studies. Thymol has been shown to induce programmed cell death (apoptosis), halt the cell division cycle (cell cycle arrest), and inhibit cancer spread (metastasis) through modulation of critical signaling pathways, including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mechanistic target of rapamycin (mTOR), and Wnt/ß-catenin. It also enhances the efficacy of 5-fluorouracil (5-FU) in colorectal cancer treatments. Thymol's broad-spectrum anticancer activities and non-toxic profile to normal cells underscore its potential as an adjunct in cancer therapy. Further clinical trials are essential to fully understand its therapeutic benefits and integration into existing treatment protocols.

Insights into Nimbolide molecular crosstalk and its anticancer properties.

Nimbolide, one of the main ingredients constituent of Azadirachta indica (neem) leaf extract, has garnered attention for its potential as an anticancer agent. Its efficacy against various cancers and chemopreventive action has been demonstrated through numerous in vivo and in vitro studies. This updated review aims to comprehensively explore the chemopreventive and anticancer properties of nimbolide, emphasizing its molecular mechanisms of action and potential therapeutic applications in oncology. The review synthesizes evidence from various studies that examine nimbolide's roles in apoptosis induction, anti-proliferation, cell death, metastasis inhibition, angiogenesis suppression, and modulation of carcinogen-metabolizing enzymes. Nimbolide exhibits multifaceted anticancer activities, including the modulation of multiple cell signaling pathways related to inflammation, invasion, survival, growth, metastasis, and angiogenesis. However, its pharmacological development is still in the early stages, mainly due to limited pharmacokinetic and comprehensive long-term toxicological studies. Nimbolide shows promising anticancer and chemopreventive properties, but there is need for systematic preclinical pharmacokinetic and toxicological research. Such studies are essential for establishing safe dosage ranges for first-in-human clinical trials and further advancing nimbolide's development as a therapeutic agent against various cancers. The review highlights the potential of nimbolide in cancer treatment and underscores the importance of rigorous preclinical evaluation to realize its full therapeutic potential.

Maximizing arsenic trioxide's anticancer potential: Targeted nanocarriers for solid tumor therapy.

Arsenic trioxide (ATO) has gained significant attention due to its promising therapeutic effects in treating different diseases, particularly acute promyelocytic leukemia (APL). Its potent anticancer mechanisms have been extensively studied. Despite the great efficacy ATO shows in fighting cancers, drawbacks in the clinical use are obvious, especially for solid tumors, which include rapid renal clearance and short half-life, severe adverse effects, and high toxicity to normal cells. Recently, the emergence of nanomedicine offers a potential solution to these limitations. The enhanced biocompatibility, excellent targeting capability, and desirable effectiveness have attracted much interest. Therefore, we summarized various nanocarriers for targeted delivery of ATO to solid tumors. We also provided detailed anticancer mechanisms of ATO in treating cancers, its clinical trials and shortcomings as well as the combination therapy of ATO and other chemotherapeutic agents for reduced drug resistance and synergistic effects. Finally, the future study direction and prospects were also presented.

Hawthorn with "homology of medicine and food": a review of anticancer effects and mechanisms.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn's anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.

The potential roles of gossypol as anticancer agent: advances and future directions.

Gossypol, a polyphenolic aldehyde derived from cottonseed plants, has seen a transformation in its pharmaceutical application from a male contraceptive to a candidate for cancer therapy. This shift is supported by its recognized antitumor properties, which have prompted its investigation in the treatment of various cancers and related inflammatory conditions. This review synthesizes the current understanding of gossypol as an anticancer agent, focusing on its pharmacological mechanisms, strategies to enhance its clinical efficacy, and the status of ongoing clinical evaluations.The methodological approach to this review involved a systematic search across several scientific databases including the National Center for Biotechnology Information (NCBI), PubMed/MedLine, Google Scholar, Scopus, and TRIP. Studies were meticulously chosen to cover various aspects of gossypol, from its chemical structure and natural sources to its pharmacokinetics and confirmed anticancer efficacy. Specific MeSH terms and keywords related to gossypol's antineoplastic applications guided the search strategy.Results from selected pharmacological studies indicate that gossypol inhibits the Bcl-2 family of anti-apoptotic proteins, promoting apoptosis in tumor cells. Clinical trials, particularly phase I and II, reveal gossypol's promise as an anticancer agent, demonstrating efficacy and manageable toxicity profiles. The review identifies the development of gossypol derivatives and novel carriers as avenues to enhance therapeutic outcomes and mitigate adverse effects.Conclusively, gossypol represents a promising anticancer agent with considerable therapeutic potential. However, further research is needed to refine gossypol-based therapies, explore combination treatments, and verify their effectiveness across cancer types. The ongoing clinical trials continue to support its potential, suggesting a future where gossypol could play a significant role in cancer treatment protocols.