Anticancer Research Articles

Anticancer Tetranuclear Cu(I) Complex Catalyzes a Click Reaction to Synthesize a Chemotherapeutic Agent in situ to Achieve Targeted Dual-Agent Combination Therapy for Cancer.

To develop next-generation metal-based drugs and dual-drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual-agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). We also constructed an apoferritin (AFt)-Cu4 nanoparticles (NPs) delivery system. AFt-Cu4 NPs not only showed an enhanced performance of tumor growth inhibition, but also improved the targeting ability and reduced the systemic toxicity of Cu4 in vivo. Importantly, the anticancer effect was enhanced by combining the AFt-Cu4 NPs with the resveratrol analogue obtained from the CuAAC reaction in situ. Finally, we revealed the anticancer mechanism of the Cu4/AFt-Cu4 NPs, which involves both cuproptosis and cuproptosis-induced systemic immune response.

Probiotics as a potential tool for gynecological cancers prevention and therapy suport

The human body is host to a variety of microbial species that are essential for maintaining general health. About nine percent of these microbial species inhabit the urogenital tract. It is therefore important to establish a symbiotic relationship between the host’s immune system and the microbiota in this region. Disruptions of this symbiosis can contribute to the development of pelvic inflammatory disease (PID), bacterial vaginosis (BV), vaginal candidiasis and/or even gynaecological cancers by promoting the proliferation of infectious agents. The chemotherapeutic agents currently used in cancer treatment are associated with undesirable side effects. Therefore, there is an urgent need for antitumor agents that have minimal toxicity compared to conventional treatments. Furthermore, the use of drugs to prevent or alleviate the side effects of cervical cancer treatment could significantly improve the quality of life of patients undergoing such therapy. In this review, we focus our attention on the potential efficacy of probiotics in both the prevention and therapeutic intervention of neoplasms affecting the genital tract.

Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemotherapy and protect against chemotherapy-induced toxicity due to its scavenging properties. Furthermore, chemical compounds in cardamom, including limonene, cymene, pinene, linalool, borneol, cardamonin, indole-3-carbinol, and diindolylmethane, primarily target the programmed cell death lignin-1 gene, which is more prevalent in cancer cells than in healthy cells. This review provides the medicinal properties and pharmacological uses of cardamom, its cellular effects, and potential therapeutic uses in cancer prevention and treatment, as well as its use in reducing drug resistance and improving the overall health of cancer patients. Based on previous preclinical studies, cardamom shows significant potential as an anti-cancer agent, but further exploration for clinical use is warranted due to its diverse mechanisms of action.

Analysis of riociguat and desmethyl riociguat by UPLC-MS/MS and its interaction with quercetin

Riociguat, an orally soluble guanylate cyclase (sGC)-promoting drug, is mainly used in the clinical treatment of pulmonary hypertension (PH). In this study, a novel ultra-performance liquid chromatography-tandem mass spectrometry method was developed to quantify the concentrations of riociguat and its metabolite (M1) in plasma. The precision, stability, accuracy, matrix effect, and recovery of the methodology were satisfactory. Quercetin, a well-recognized compound, functions as a novel anticancer agent with the potential to alleviate symptoms of PH. Therefore, the potential interaction between quercetin and riociguat was investigated in this study. The levels of riociguat and M1 in rat plasma were measured using the method developed in this study to evaluate the interactions between riociguat and quercetin in rats. The results revealed that quercetin significantly inhibited riociguat and M1 metabolism with increased systemic exposure.

Selected biological properties of quercetin, curcumin, and kaempferol

Polyphenols are a large group of organic compounds present in plants, where they play various roles pivotal to their proper physiological functioning. Polyphenols are ubiquitous in many dietary sources such as fruits, vegetables, beverages, seeds, and honeys. Diet plays a crucial role in sustaining overall well-being of the organism and preventing diseases, including cancer. Despite broad spectrum of health promoting activity of polyphenols, such as antioxidant, anti-inflammatory and antimicrobial, many of them are also potent anti-cancer compounds. In this review we focused on presentation of three polyphenols such as quercetin, curcumin, and kaempferol. We discussed recent studies concerning their beneficial impact on human health and potential as anticancer agents.

Synthesis, Molecular Docking, and Anticancer Screening of Ester-based Thiazole Derivatives.

This study investigates the potential of five compounds as novel anticancer agents. We examined their efficacy, mechanisms of action, and impact on various cancer cell lines, through a comprehensive set of experiments. Notably, compound 3e demonstrated superior activity compared to the positive control cisplatin, with a GI50 value of 6.3±0.7 μM against the breast cancer cell line (MCF-7). Compound 3b also displayed remarkable growth inhibition, yielding GI50 values of 8.7±0.2 μM (MCF-7) and 8.9±0.5 μM against the colon cancer cell line (HCT-116). Cell count experiments further confirmed the potent inhibitory effects of compounds 3e, 3b, and 3c on MCF-7 and HCT-116 cell growth. Compound 3e demonstrated a reduction of 55-60 % at GI50 and complete inhibition (100 %) at 2x GI50. Compound 3b exhibited 50-55 % reduction (GI50) and 90-95 % inhibition (2x GI50) in HCT-116 cells. Compound 3c displayed 75-80 % inhibition (2x GI50) and 35-40 % inhibition (GI50) in HCT-116 cells. In-depth mechanistic investigations unveiled valuable insights into the mode of action of compound 3e. The cell-cycle assay demonstrated G2/M phase arrest, DNA damage, and caspase-mediated apoptosis in both MCF-7 and HCT-116 cells. Caspase activation indicated a significant increase in apoptosis following exposure to compound 3e. Furthermore, compound 3e induced reactive oxygen species (ROS) production, influencing HCT-116 and MCF-7 cells differently. Elevated ROS production in HCT-116 cells and distinct effects in MCF-7 cells contribute to a deeper understanding of the cytotoxic mechanisms of compound 3e. Overall, these findings highlight the potential of the investigated compounds, particularly compound 3e, as effective inducers of apoptosis in cancer cells. Mechanistic insights into cell cycle arrest, caspase-mediated apoptosis, and ROS modulation provide a comprehensive understanding of their cytotoxic effects. This study offers significant contribution to the development of promising anticancer agents and their therapeutic applications.

Plectalibertellenone A suppresses colorectal cancer cell motility and glucose metabolism by targeting TGF-β/Smad and Wnt pathways.

Colorectal cancer (CRC) is the second most common cause of cancer-related death and represents a serious worldwide health problem. CRC metastasis decreases the survival rate of cancer patients, underscoring the need to identify novel anticancer agents and therapeutic targets. Here, we introduce Plectalibertellenone A (B) as a promising agent for the inhibition of CRC cell motility and glucose metabolism and explore its mechanism of action in CRC cells. Plectalibertellenone A suppressed TGF-β gene expression and the activation of the TGF-β/Smad signaling pathway, leading to reverse epithelial to mesenchymal transition (EMT) by modulating the expressions of EMT markers and transcriptional factors such as E-cadherin, N-cadherin, vimentin, Slug, Snail, Twist, and ZEB1/2. Furthermore, disruption of Wnt signaling inhibited CRC motility and glucose metabolism including glycolysis and oxidative phosphorylation, primarily affecting glycolytic enzymes, GLUT1, HK2, PKM2, LDHA, and HIF-1α under hypoxic condition. Therefore, Plectalibertellenone A is a potential drug candidate that can be developed into a promising anticancer treatment to prevent CRC metastasis and inhibit glucose metabolism.

Semicarbazone, thiosemicarbazone tailed isoxazoline-pyrazole: synthesis, DFT, biological and computational assessment.

Aim: A series of semicarbazone and thiosemicarbazone-tailed hybrids comprising pyrazole and acetylisoxazoline were prepared from (R)-carvone and characterized by technique spectroscopies Nuclear Magnetic Resonance (NMR), IR and High-Resolution Mass Spectrometry. Density Functional Theory (DFT)determined the structural parameters. Their cytotoxic activity was evaluated in vitro against four human cancer cell lines.Methods & results: All the studied semi and thiosemicarbazone demonstrate a promising potential as anticancer agents. The mechanism of action of these compounds involves apoptosis in HT-1080 cells, supported by an increase in the level of caspase-3/7 activity, which also arrests the cell cycle in the G0/G1 phase. Molecular docking studies were performed to establish the potential of the most active compounds 4a and 5a. ADMET analysis showed appropriate pharmacokinetic properties, allowing structure prediction for anticancer activity.

Drug-induced lung disease: a narrative review

Drug-induced lung disease (DILD) encompasses a broad, highly heterogeneous group of conditions that may occur as a result of exposure to numerous agents, such as antineoplastic drugs, conventional or biological disease-modifying antirheumatic drugs, antiarrhythmics, and antibiotics. Between 3% and 5% of prevalent cases of interstitial lung diseases are reported as DILDs. The pathogenesis of lung injury in DILD is variable, multifactorial, and often unknown. Acute presentation is the most common, can occur from days to months after the start of treatment, and ranges from asymptomatic to acute respiratory failure. The CT patterns are varied and include ground-glass opacities, organizing pneumonia, and diffuse alveolar damage. Notably, there are no clinical manifestations or CT patterns specific to DILD, which makes the diagnosis quite challenging and necessitates a high index of suspicion, as well as the exclusion of alternative causes such as infection, cardiac-related pulmonary edema, exacerbation of a preexisting ILD, and neoplastic lung involvement. Discontinuation of the offending medication constitutes the cornerstone of treatment, and corticosteroid treatment is usually necessary after the onset of clinical manifestations. The prognosis varies widely, with high mortality rates in severe cases. A history of medications related to pulmonary toxicity in patients with new-onset respiratory symptoms should prompt consideration of DILD as a potential underlying cause.

Evaluation of Left Atrial Electromechanical Delay and Left Atrial Phasic Functions in Patients Undergoing Treatment with Cardiotoxic Chemotherapeutic Agents

Background: The aim of this study is to evaluate atrial involvement by comparing pre- and post-chemotherapy left atrial mechanical and electromechanical parameters in patients treated with cardiotoxic chemotherapeutic agents. Methods: We designed our study as a prospective cohort study. Sixty-eight female patients between the ages of 18 and 50, scheduled for treatment with cardiotoxic chemotherapeutic agents, were included in our study. Atrial mechanical functions and electromechanical parameters were examined and compared with basic echocardiographic parameters before and after chemotherapy. Results: The mean age of the patients was 41.6 ± 7.9 years. After chemotherapy, lateral PA, septal PA, and tricuspid PA durations showed a significant increase (p < 0.001), but there were no statistically significant changes in the left intra-atrial electromechanical delay, the right intra-atrial electromechanical delay, or the interatrial electromechanical delay values. Following treatment, LAVmax, LAVmin, and LApreA significantly increased (p < 0.001). Additionally, the left atrial passive and active emptying volumes increased (p < 0.001), while the reservoir and pump (active emptying) functions decreased (with p-values of 0.03 and 0.01, respectively). The passive emptying function, however, showed no significant change (p = 0.65). Decreases in LVEF were observed, while LVEDD, LVESD, IVS, PW, and LA diameters increased (p-value of 0.02 for IVS and <0.001 for the others). Conclusions: Significant impairment of atrial mechanical functions and electromechanical parameters was observed after treatment with cardiotoxic chemotherapeutic agents. This suggests an elevated likelihood of atrial arrhythmia linked to the use of cardiotoxic chemotherapeutic agents.

Intelligence computational analysis of letrozole solubility in supercritical solvent via machine learning models

Supercritical fluids (SCFs) can be used to prepare drugs nanoparticles with improved solubility. SCFs have shown superior advantages in pharmaceutical industry as an environmentally friendly alternative to toxic/harmful organic solvents. They possess gas-like transport characteristics and liquid-like solvation power for solutes. Evaluation of chemotherapeutic drugs’ solubility in supercritical carbon dioxide (SCCO2) has been recently an attractive subject for developing this method in pharmaceutical sector. To reach this purpose, the utilization of accurate models is of great necessity to estimate experimental-based solubility data. In this paper, the authors tried to employ machine learning (ML) approaches to estimate the solubility of Letrozole (LET) drug as chemotherapeutic agent and correlate its values in wide ranges of temperature and pressure. To do this, PAR (Passive Aggressive Regression), RF (Random Forest), and RBF-SVM are the models used (Support Vector Machine with RBF kernel). These models optimized in terms of their hyper-parameters using GA algorithm. The optimized PAR, RF, RBF-SVM models obtained coefficients of determination (R-squared) of 0.8277, 0.9534, and 0.9947. Also, the MSE error rate of the models are 0.1342, 0.0305, and 0.0045, in the same order. The final result of the evaluations shows the optimized RBF-SVM model as the most appropriate model in this research. The model exhibits a maximum prediction error of 0.1289.

The Z isomer of pyridoxilidenerhodanine 5'-phosphate is an efficient inhibitor of human pyridoxine 5'-phosphate oxidase, a crucial enzyme in vitamin B6 salvage pathway and a potential chemotherapeutic target.

Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, acts as a cofactor in many metabolic processes. In humans, PLP is produced in the reactions catalysed by pyridox(am)ine 5'-phosphate oxidase (PNPO) and pyridoxal kinase (PDXK). Both PNPO and PDXK are involved in cancer progression of many tumours. The silencing of PNPO and PDXK encoding genes determines a strong reduction in tumour size and neoplastic cell invasiveness in models of acute myeloid leukaemia (in the case of PDXK) and ovarian and breast cancer (in the case of PNPO). In the present work, we demonstrate that pyridoxilidenerhodanine 5'-phosphate (PLP-R), a PLP analogue that has been tested by other authors on malignant cell lines reporting a reduction in proliferation, inhibits PNPO in vitro following a mixed competitive and allosteric mechanism. We also show that the unphosphorylated precursor of this inhibitor (PL-R), which has more favourable pharmacokinetic properties according to our predictions, is phosphorylated by PDXK and therefore transformed into PLP-R. On this ground, we propose the prototype of a novel prodrug-drug system as a useful starting point for the development of new, potential, antineoplastic agents.

Repurposing auranofin and meclofenamic acid as energy-metabolism inhibitors and anti-cancer drugs.

Cytotoxicity of the antirheumatic drug auranofin (Aur) and the non-steroidal anti-inflammatory drug meclofenamic acid (MA) on several cancer cell lines and isolated mitochondria was examined to assess whether these drugs behave as oxidative phosphorylation inhibitors. The effect of Aur or MA for 24 h was assayed on metastatic cancer and non-cancer cell proliferation, energy metabolism, mitophagy and metastasis; as well as on oxygen consumption rates of cancer and non-cancer mitochondria. Aur doses in the low micromolar range were required to decrease proliferation of metastatic HeLa and MDA-MB-231 cells, whereas one or two orders of magnitude higher levels were required to affect proliferation of non-cancer cells. MA doses required to affect cancer cell growth were one order of magnitude higher than those of Aur. At the same doses, Aur impaired oxidative phosphorylation in isolated mitochondria and intact cells through mitophagy induction, as well as glycolysis. Consequently, cell migration and invasiveness were severely affected. The combination of Aur with very low cisplatin concentrations promoted that the effects on cellular functions were potentiated. Aur surges as a highly promising anticancer drug, suggesting that efforts to establish this drug in the clinical treatment protocols are warranted and worthy to undertake.

An Unusual Application of Multifunctional Nanozyme Derived from COF: Augmenting Chemoimmunotherapy while Attenuating Cardiotoxicity

AbstractEnhancing therapeutic efficacy while reducing the adverse effects of drugs is crucial in cancer treatments. In this study, nitrogen‐doped carbon nanospheres are synthesized with variable enzymatic activities through the pyrolysis of a covalent organic framework (COF). These nanospheres show increased peroxidase (POD) and oxidase (OXD) activities in the tumor microenvironment, generating reactive oxygen species (ROS) that help eliminate tumor cells. Under normal conditions, they display catalase (CAT) and superoxide dismutase (SOD) activities, promoting antioxidative protection. Their porous structure and π–π/hydrophobic interactions allow for the loading of the chemotherapeutic agent doxorubicin (DOX). The nanospheres are then enveloped by tumor cell membranes, stabilizing the drug load and enabling targeted drug delivery with pH‐sensitive release. This targeted system induces ferroptosis in tumor cells and activates a strong anti‐tumor immune response, leading to enhanced immunotherapy for breast cancer and reduced tumor metastasis to the lungs. Importantly, the varied enzymatic activities of the nanomedicine system help mitigate the cardiotoxicity of DOX chemotherapy, improving cancer treatment while minimizing side effects. This approach introduces a nano‐enzyme drug system with distinctive activities and innovative preparation, setting a new standard for efficient, low‐toxicity cancer therapy.

Multifunctional gallium doped bioactive glasses: a targeted delivery for antineoplastic agents and tissue repair against osteosarcoma

Osteosarcoma (OS) is the mostly commonly occurring primary bone cancer. Despite comprehensive treatment programs including neoadjuvant chemotherapy and tumour resection, survival rates have not improved significantly since the 1970s. Survival rates are dramatically reduced for patients who suffer a local recurrence. Furthermore, primary bone cancer patients are at increased risk of bone fractures. Consequently, there is an urgent need for alternative treatment options. In this paper we report the development of novel gallium doped bioactive glass that selectively kill bone cancer cells whilst simultaneously stimulating new bone growth. Here we show, using a combination of 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide, LIVE/DEAD assays and image analysis, that bioactive glasses containing gallium oxide are highly toxic and reduce both the proliferation and migration of bone cancer cells (Saos-2) in a dose dependant manner. Glasses containing 5 mol% gallium oxide reduced the viability of OS cells by 99% without being cytotoxic to the non-cancerous normal human osteoblasts (NHOst) control cells. Furthermore, Fourier transform infrared and energy-dispersive x-ray spectroscopy results confirmed the formation of an amorphous calcium phosphate/hydroxyapatite like layer on the surface of the bioactive glass particulates, after 7 d incubating in simulated body fluid, indicating the early stages of bone formation. These materials show significant potential for use in bone cancer applications as part of a multimodal treatment.

Exosomal fragment enclosed polyamine-salt nano-complex for co-delivery of docetaxel and mir-34a exhibits higher cytotoxicity and apoptosis in breast cancer cells

A novel core–shell nanocarrier system has been designed for co-delivery of a small anticancer drug, docetaxel (DTX) and tumor suppressor (TS) miR-34a named as Exo(PAN34a+DTX). The core is formed by pH dependent polyamine salt aggregates (PSA) containing both the payloads and the shell is formed by RAW 264.7 cell derived exosomal fragments. Herein, phosphate driven polyallylamine hydrochloride (PAH, MW:17,500 Da) PSA was formed in presence of miR-34a and DTX to form PAN34a+DTX. The formulation exhibited pH dependent DTX release with only 33.55 ± 2.12% DTX release at pH 7.2 and 75.21 ± 1.8% DTX release till 144 h at pH 5.5. At 1.21 molar ratio of phosphate to the amine (known as R value), efficient complexation of miR-34a (3.6 μM) in the PAN particles was obtained. PAN34a+DTX demonstrated particle size (163.86 ± 12.89 nm) and zeta-potential value of 17.53 ± 5.10 mV which upon exosomal fragment layering changed to − 7.23 ± 2.75 mV which is similar to the zeta-potential of the exosomal fragments, i.e., − 8.40 ± 1.79 mV. The final formulation Exo(PAN34a+DTX), loaded with 40 ng/mL DTX and 50 nM miR-34a exhibited 48.20 ± 4.59% cytotoxicity in triple negative breast cancer (TNBC) cells, 4T1. Co-localization of CM-DiI (red fluorescence) stained exosomal fragments and FAM-siRNA (green fluorescence) in the cytoplasm of 4T1 cells after 6 h of Exo(PANFAM) treatment confirmed the efficiency of the designed system to co-deliver two actives. Exo(PAN34a+DTX) also reduced BCL-2 expression (target gene for miR-34a) by 8.98 folds in comparison to free DTX confirming promising co-delivery and apoptosis inducing effect of Exo(PAN34a+DTX) in 4T1.

COVID-19 in patients receiving treatment at an outpatient chemotherapy unit.

During the COVID-19 pandemic period, many patients who required outpatient chemotherapy developed COVID-19, requiring chemotherapy interruption. However, there are no clear guidelines regarding the safe timing for restarting chemotherapy. We conducted a retrospective study to assess when such patients can safely recommence chemotherapy. Of the 40 patients included in this study, 34 restarted anticancer drug therapy after COVID-19 infection. Six patients, four with multiple myeloma, and one each with follicular lymphoma and glioma, remained SARS-CoV-2 antigen positive >20days after COVID-19 onset. Multiple myeloma patients recorded significantly higher frequencies of SARS-CoV-2 antigen positivity >20days after COVID-19 onset compared with solid tumor patients, with no significant differences in the frequency of SARS-CoV-2 positivity during 5-20days from COVID-19 onset between them. According to our data, most solid tumor patients achieved SARS-CoV-2 antigen negativity after 20days from COVID-19 onset. On the other hand, multiple myeloma patients might need serial antigen tests before restarting anticancer therapy in the outpatient chemotherapy setting.

Identification of telomere-related lncRNAs and immunological analysis in ovarian cancer

BackgroundOvarian cancer (OC) is a global malignancy characterized by metastatic invasiveness and recurrence. Long non-coding RNAs (lncRNAs) and Telomeres are closely connected with several cancers, but their potential as practical prognostic markers in OC is less well-defined.MethodsRelevant mRNA and clinical data for OC were sourced from The Cancer Genome Atlas (TCGA) database. The telomere-related lncRNAs (TRLs) prognostic model was established by univariate/LASSO/multivariate regression analyses. The effectiveness of the TRLs model was evaluated and measured via the nomogram. Additionally, immune infiltration, tumor mutational load (TMB), and drug sensitivity were evaluated. We validated the expression levels of prognostic genes. Subsequently, PTPRD-AS1 knockdown was utilized to perform the CCK8 assay, colony formation assay, transwell assay, and wound healing assay of CAOV3 cells.ResultsA six-TRLs prognostic model (PTPRD-AS1, SPAG5-AS1, CHRM3-AS2, AC074286.1, FAM27E3, and AC018647.3) was established, which can effectively predict patient survival rates and was successfully validated using external datasets. According to the nomogram, the model could effectively predict prognosis. Furthermore, we detected the levels of regulatory T cells and M2 macrophages were comparatively higher in the high-risk TRLs group, but the levels of activated CD8 T cells and monocytes were the opposite. Finally, the low-risk group was more sensitive to anti-cancer drugs. The mRNA levels of PTPRD-AS1, SPAG5-AS1, FAM27E3, and AC018647.3 were significantly over-expressed in OC cell lines (SKOV3, A2780, CAOV3) in comparison to normal IOSE-80 cells. AC074286.1 were over-expressed in A2780 and CAOV3 cells and CHRM3-AS2 only in A2780 cells. PTPRD-AS1 knockdown decreased the proliferation, cloning, and migration of CAOV3 cells.ConclusionOur study identified potential biomarkers for the six-TRLs model related to the prognosis of OC.

Targeting therapy-persistent residual disease.

Disease relapse driven by acquired drug resistance limits the effectiveness of most systemic anti-cancer agents. Targeting persistent cancer cells in residual disease before relapse has emerged as a potential strategy for enhancing the efficacy and the durability of current therapies. However, barriers remain to implementing persister-directed approaches in the clinic. This Perspective discusses current preclinical and clinical complexities and outlines key steps toward the development of clinical strategies that target therapy-persistent residual disease.

Exploring the interplay of natural products and long non-coding RNAs in colorectal cancer: pathogenesis, diagnosis, and overcoming drug resistance.

Colorectal cancer (CRC) is recognized as one of the most prevalent malignancies, both in terms of incidence and mortality rates. Current research into CRC has shed light on the molecular mechanisms driving its development. Several factors, including lifestyle, environmental influences, genetics, and diet, play significant roles in its pathogenesis. Natural compounds such as curcumin, tanshinone, lycorine, sinomenine, kaempferol, verbascoside, quercetin, berberine, and fisetin have shown great promise in the prevention and treatment of CRC. Research has also highlighted the significance of non-coding RNAs (ncRNAs) as biomarkers and therapeutic targets in CRC. Among these, long non-coding RNAs (lncRNAs) have been found to regulate the transcription of genes involved in cancer. LncRNAs contribute to cancer stem cell (CSC) proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and chemoresistance. Specific lncRNAs, including GAS5, LNC00337, HOTAIR, TPT1-AS1, cCSC1, BCAR4, TUG1, and Solh2, play crucial roles in these processes. They hold potential as novel biomarkers, detectable in bodily fluids and tissues, and could serve as therapeutic targets due to their involvement in drug resistance and sensitivity. These insights could improve CRC treatment strategies, addressing resistance to chemotherapy and radiotherapy. This review article aims to provide a comprehensive analysis of the current knowledge regarding the effectiveness of natural anti-cancer agents in CRC treatment. Additionally, it offers an in-depth evaluation of lncRNAs in CRC, their role in the disease's progression, and their potential applications in its management.