Apoptosis In Different Types Research Articles

Results of Immunohistochemical Studies of Expression of Markers of Cell Cycle Regulation, Proliferation and Apoptosis in Different Types of Neoplasia of the Accessory Lub of the Mammary Gland

Results of Immunohistochemical Studies of Expression of Markers of Cell Cycle Regulation, Proliferation and Apoptosis in Different Types of Neoplasia of the Accessory Lub of the Mammary Gland

Proteomic characterization of extracellular vesicles in programmed cell death.

Programmed cell death (PCD) is a fundamental biological process that plays a critical role in cell development, differentiation, and homeostasis. The secretion and uptake of extracellular vesicles (EVs) is one of the important regulatory mechanisms for PCD. EVs are natural membrane structures secreted by cells that contain a variety of proteins, lipids, nucleic acids, and other bioactive molecules. Due to their important roles in intercellular communication and disease progression, there is great interest in studying EVs and their cargo. Different protein components are sorted and packaged in EVs, allowing EVs to perform their functions. The study of EV proteomics helps us understand the role of PCD in the development of diseases. Meanwhile, proteomics is a powerful tool for studying the composition and function of EVs, which assists in the identification, quantification, and profiling of protein components of EVs, and provides insight into the molecular mechanisms involved in PCD and related diseases. In this review, we summarize the characteristics of EV proteomics in different types of PCD, compare different proteomic profiling strategies for EVs, and discuss the impact of EV proteomics on cell function and regulation during PCD, to understand its role in the pathogenesis of related diseases.

Identification and analysis of diverse cell death patterns in diabetic kidney disease using microarray-based transcriptome profiling and single-nucleus RNA sequencing

BackgroundDiabetic kidney disease (DKD) is the most lethal complication of diabetes. Diverse programmed cell death (PCD) has emerged as a crucial disease phenotype that has the potential to serve as an indicator of renal function decline and can be used as a target for researching drugs for DKD. MethodsMicroarray-based transcriptome profiling and single-nucleus transcriptome sequencing (snRNA-seq) related to DKD were retrieved from the Gene Expression Omnibus (GEO) database. 13 PCD-related genes (including alkaliptosis, apoptosis, autophagy-dependent cell death, cuproptosis, disulfidptosis, entotic cell death, ferroptosis, lysosome-dependent cell death, necroptosis, netotic cell death, oxeiptosis, parthanatos, and pyroptosis) were obtained from various public databases and reviews. The gene set variation analysis (GSVA) analysis was used to explore the pathway activity of these 13 PCDs in DKD, and the pathway activity of these PCDs in different renal cells was studied based on DKD-related snRNA-seq data. To identify the core PCDs that play a significant role in DKD, we analyzed the relationships between different types of PCD and immune infiltration, fibrosis-related gene expression levels, glomerular filtration rate (GFR), and diagnostic efficiency in DKD. Using the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm, we screened for core death genes among the core PCDs and constructed a cell death-related signature (CDS) risk score based on the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, we validated the predictive performance of the CDS risk score in an independent validation set. ResultsWe identified 4 core PCD pathways, namely entotic cell death, apoptosis, necroptosis, and pyroptosis in DKD, and further applied the WGCNA algorithm to screen 4 core death genes (CASP1, CYBB, PLA2G4A, and CTSS) and constructed a CDS risk score based on these genes. The CDS risk score demonstrated high diagnostic efficiency for DKD patients, and those with higher scores had higher levels of immune cell infiltration and poorer GFR. ConclusionOur study sheds light on the fact that multiple PCDs contribute to the progression of DKD, highlighting potential therapeutic targets for treating this disease.

The role of exosomes in cancer-related programmed cell death.

Cancer arises from the growth and division of uncontrolled erroneous cells. Programmed cell death (PCD), or regulated cell death (RCD), includes natural processes that eliminate damaged or abnormal cells. Dysregulation of PCD is a hallmark of cancer, as cancer cells often evade cell death and continue to proliferate. Exosomes nanoscale extracellular vesicles secreted by different types of cells carrying a variety of molecules, including nucleic acids, proteins, and lipids, to have indispensable role in the communication between cells, and can influence various cellular processes, including PCD. Exosomes have been shown to modulate PCD in cancer cells by transferring pro- or antideath molecules to neighboring cells. Additionally, exosomes can facilitate the spread of PCD to surrounding cancer cells, making them promising in the treatment of various cancers. The exosomes' diagnostic potential in cancer is also an active area of research. Exosomes can be isolated from a wide range of bodily fluids and tissues, such as blood and urine, and can provide a noninvasive way to monitor cancer progression and treatment response. Furthermore, exosomes have also been employed as a delivery system for therapeutic agents. By engineering exosomes to carry drugs or other therapeutic molecules, they can be targeted specifically to cancer cells, reducing toxicity to healthy tissues. Here, we discussed exosomes in the diagnosis and prevention of cancers, tumor immunotherapy, and drug delivery, as well as in different types of PCD.

Advancements in Laser and Ultrasound Therapeutic Strategies for Cancer Cells: Recent Review

Cancer is a disease caused by uncontrollable cell growth and division. Surgery, chemotherapy, radiotherapy, and hormonotherapy are all cancer treatment options. In addition to noninvasive cancer ablative therapy. As an example, ultrasonic therapy, even with low-intensity pulsed ultrasound (LIPUS) or high-intensity focused ultrasound (HIFU), and Laser therapy (photo-biomodulation therapy) in low-level laser therapy (LLLT) with different wavelength ranges from ultraviolet (UV), visible and infrared (IR) that all have demonstrated different results depending on the target of treatment so previous trials therapies are being studied. This paper reviews recent studies on the in vitro treatment effect of ultrasound therapy and laser therapy on normal and cancerous cell lines with specific parameters. The effect of ultrasound results showed a decrease in cell proliferation and an increase in apoptosis in different types of cells, depending especially on sound intensity, known as Special Peak Temporal Average Intensity (ISPTA). While the laser effect is noticed on cell viability, either enhance or inhibit their viability depending upon the dose of exposure and other specific parameters like wavelength, energy density, and power density used in each treatment protocol. The previous studies conclude that each response would have a treatment method with specific parameters, even an increase or decrease in cell viability. Further studies need to be applying these methods in vivo.

Pyroptosis Inhibition in Disease Treatment: Opportunities and Challenges.

Programmed cell death (PCD) is at the center of immune responses, with different types of PCD occurring based on bodily conditions at a given moment. The main three types of PCD include pyroptosis, necroptosis, and apoptosis. Both pyroptosis and necroptosis induce an inflammatory response while apoptosis avoids eliciting an inflammatory reaction. Recently, pyroptosis has come to the forefront of immunology research due to tremendous potential that has been revealed surrounding the regulators of pyroptosis. In addition to previously known regulators of pyroptosis (ZBP1 and NLRP3 genes), a family of proteins called Gasdermin has been discovered. Specifically, Gasdermin D (GSDMD), when cleaved, participates in the onset of pyroptosis of inflammatory diseases. The N-terminal cleaved portion of the molecule causes cellular membrane openings releasing interleukin-18 and IL-1β, inducing pyroptosis. It is hypothesized that the inhibition of GSDMD using drugs such as Dimethyl Fumarate (DMF) and Disulfiram may halt the progression of certain inflammatory diseases including Multiple Sclerosis (MS), autoimmune encephalitis etc. While there is not yet a concrete treatment for pyroptic cell death in inflammatory disease using GSDMD inhibition, there is ample evidence to suggest that there may be success in future studies and therapeutic applications of GSDMD.

Naturally Occurring Phytochemicals to Target Breast Cancer Cell Signaling.

Almost 70% of clinically used antineoplastic drugs are originated from natural products such as plants, marine organism, and microorganisms and some of them are also structurally modified natural products. The naturally occurring drugs may specifically act as inducers of selective cytotoxicity, anti-metastatic, anti-mutagenic, anti-angiogenesis, antioxidant accelerators, apoptosis inducers, autophagy inducers, and cell cycle inhibitors in cancer therapy. Precisely, several reports have demonstrated the involvement of naturally occurring anti-breast cancer drugs in regulating the expression of oncogenic and tumor suppressors associated with carcinogen metabolism and signaling pathways. Anticancer therapies based on nanotechnology have the potential to improve patient outcomes through targeted therapy, improved drug delivery, and combination therapies. This paper has reviewed the current treatment for breast cancer and the potential disadvantages of those therapies, besides the various mechanism used by naturally occurring phytochemicals to induce apoptosis in different types of breast cancer. Along with this, the contribution of nanotechnology in improving the effectiveness of anticancer drugs was also reviewed. With the development of sciences and technologies, phytochemicals derived from natural products are continuously discovered; however, the search for novel natural products as chemoprevention drugs is still ongoing, especially for the advanced stage of breast cancer. Continued research and development in this field hold great promise for advancing cancer care and improving patient outcomes.

BCL2L13 promotes mitophagy through DNM1L-mediated mitochondrial fission in glioblastoma

There is an urgent need for novel diagnostic and therapeutic strategies for patients with Glioblastoma multiforme (GBM). Previous studies have shown that BCL2 like 13 (BCL2L13) is a member of the BCL2 family regulating cell growth and apoptosis in different types of tumors. However, the clinical significance, biological role, and potential mechanism in GBM remain unexplored. In this study, we showed that BCL2L13 expression is significantly upregulated in GBM cell lines and clinical GBM tissue samples. Mechanistically, BCL2L13 targeted DNM1L at the Ser616 site, leading to mitochondrial fission and high mitophagy flux. Functionally, these alterations significantly promoted the proliferation and invasion of GBM cells both in vitro and in vivo. Overall, our findings demonstrated that BCL2L13 plays a significant role in promoting mitophagy via DNM1L-mediated mitochondrial fission in GBM. Therefore, the regulation and biological function of BCL2L13 render it a candidate molecular target for treating GBM.

A bibliometric analysis of programmed cell death in acute lung injury/acute respiratory distress syndrome from 2000 to 2022

Acute lung injury (ALI) is a prevalent critical disorder that disrupts the body's homeostasis in patients. The progression from ALI to acute respiratory distress syndrome (ARDS) is often accompanied by programmed cell death (PCD). However, there has been a lack of systematic research and comprehensive analysis on the role of different types of PCD in ALI/ARDS. This study aims to analyze the research status, trends, research hotspots, and compare the contribution of publications from different countries, institutions, journals and authors in the field of PCD in ALI/ARDS using bibliometric analysis. We collected publications regard to PCD and ALI/ARDS from Web of Science during 2000–2022. VOSviewer, Citespace, Scimago Graphica, Pajek, and GraphPad Prism 9.0 software were used for further analyzed and visualized. We identified a total of 3495 publications. The number of publications has increased since the beginning of the new century. China produced the most publications (1965), while the United States ranks first in the number of citations (40141). Shanghai Jiao Tong University and American Journal of Physiology-Lung Cellular and Molecular Physiology were the most prolific institution and journal, respectively. Wang, Ping has published most papers (23) while publications from Lee, Pj have most citations (2016). In terms of keywords, “apoptosis” and “inflammation” are the most frequently occurring, but there has been a recent shift from “apoptosis” and “autophagy” to “necroptosis”, “pyroptosis”, and “ferroptosis”. Additionally, COVID-19 and long noncoding RNA (lncRNA) have become research hotspots in recent years. In conclusion, this bibliometric analysis reveals the research directions and frontier hotspots of PCD in ALI/ARDS. China and the United States have made important contributions to the development of this field. The research hotspots have recently focused on necroptosis, pyroptosis, ferroptosiss, COVID-19 and lncRNA.

Programmed Cell Death in Sea Urchins: A Review

The sea urchin embryo is a widespread model system useful to study fundamental biological processes, but also for the identification of molecular and cellular mechanisms activated in response to external stress factors. Programmed cell death (PCD) is a molecular mechanism regulated at the genomic level and conserved during evolution, playing a central role in the rearrangement and shaping of tissues in developing embryos, especially during metamorphosis, also activated in response to damages induced by abiotic stress. Currently, different types of PCD have been described, among which apoptosis and autophagy are the most conserved processes among metazoans. These processes can be activated as alternative or combined defense strategies in embryos exposed to different types of stress when repairing mechanisms (activation of Heath Shock Proteins and Metallothioneins, DNA repair), fail to rescue cell viability. In this review, we report on the available information concerning the possible involvement of PCD processes in sea urchin embryos following exposure to pollutants, including heavy metals, physical factors and toxic natural compounds. We also report information about the occurrence of physiological apoptosis during development.

A bibliometric analysis of ferroptosis, necroptosis, pyroptosis, and cuproptosis in cancer from 2012 to 2022

This study aims to visualize research hotspots and trends of “ferroptosis in cancer”, “necroptosis in cancer”, “pyroptosis in cancer”, and “cuproptosis in cancer” through a bibliometric analysis to facilitate understanding of future developments in basic and clinical research and to provide a new perspective on cancer treatment. From January 1, 2012 to October 31, 2022, in the field of “ferroptosis in cancer”, a total of 2467 organizations from 79 different countries published 3302 articles. 2274 organizations from 72 different countries published 2233 articles in the field of “ necroptosis in cancer”. 1366 institutions from 58 different countries contributed 1445 publications in the field of “pyroptosis in cancer”. In the field of “ cuproptosis in cancer”, the number of articles published in the last 10 years is relatively low, with a total of 109 articles published by 116 institutions from four different countries. In the field of “ferroptosis in cancer”, Tang Daolin had published 66 documents, ranked the first, while Dixon SJ is the most cited author, cited 3148 times; In the fields of “necroptosis in cancer”, Vandenabeele peter had published 35 papers and Degterev had been cited 995 times, ranked the first, respectively; Kanneganti thirumala-devi had published 24 papers, is the highest number of publications in the fields of “pyroptosis in cancer”, while Shi JJ was the most cited author with being cited 508 times. Both Huang Yan and Wang Tao published three papers and tied for first place and Tsvetkov p ranks first with being cited 107 times in “cuproptosis in cancer”. “Cell”, “Cell”, “Nature”, and “Science” was the most frequently co-cited journal on “ferroptosis in cancer”, “necroptosis in cancer”, “pyroptosis in cancer”, and “cuproptosis in cancer”, respectively. Further exploration of inhibitors of different Programmed cell death (PCD) and their targeted therapies are potential treatment options for cancer, but more direct clinical evidence as well as higher level clinical trials remain to be explored. Further clarification of the mechanisms of crosstalk between these PCDs may provide effective cancer treatments. And the role of different types of PCDs, especially the novel ones discovered, in cancer can be expected to remain a hot topic of research in the cancer field for quite some time to come.

Programmed cell death and lipid metabolism of macrophages in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has now become the leading chronic liver disease worldwide with lifestyle changes. This may lead to NAFLD becoming the leading cause of end-stage liver disease in the future. To date, there are still no effective therapeutic drugs for NAFLD. An in-depth exploration of the pathogenesis of NAFLD can help to provide a basis for new therapeutic agents or strategies. As the most important immune cells of the liver, macrophages play an important role in the occurrence and development of liver inflammation and are expected to become effective targets for NAFLD treatment. Programmed cell death (PCD) of macrophages plays a regulatory role in phenotypic transformation, and there is also a certain connection between different types of PCD. However, how PCD regulates macrophage polarization has still not been systematically elucidated. Based on the role of lipid metabolic reprogramming in macrophage polarization, PCD may alter the phenotype by regulating lipid metabolism. We reviewed the effects of macrophages on inflammation in NAFLD and changes in their lipid metabolism, as well as the relationship between different types of PCD and lipid metabolism in macrophages. Furthermore, interactions between different types of PCD and potential therapeutic agents targeting of macrophages PCD are also explored.

Involvement of the Actin Machinery in Programmed Cell Death.

Programmed cell death (PCD) depicts a genetically encoded and an orderly mode of cellular mortality. When triggered by internal or external stimuli, cells initiate PCDs through evolutionary conserved regulatory mechanisms. Actin, as a multifunctional cytoskeleton protein that forms microfilament, its integrity and dynamics are essential for a variety of cellular processes (e.g., morphogenesis, membrane blebbing and intracellular transport). Decades of work have broadened our knowledge about different types of PCDs and their distinguished signaling pathways. However, an ever-increasing pool of evidences indicate that the delicate relationship between PCDs and the actin cytoskeleton is beginning to be elucidated. The purpose of this article is to review the current understanding of the relationships between different PCDs and the actin machinery (actin, actin-binding proteins and proteins involved in different actin signaling pathways), in the hope that this attempt can shed light on ensuing studies and the development of new therapeutic strategies.

Anticancer Efficacy and Mechanism of Amentoflavone for Sensitizing Oral Squamous Cell Carcinoma to Cisplatin.

Nuclear factor kappa B (NF-κB) inactivation and apoptosis activation have been shown to enhance the anticancer effect of cisplatin in oral squamous cell carcinoma (OSCC). Amentoflavone may suppress NF-κB activity and trigger apoptosis in different types of cancer. The aim of this study was to investigate the anticancer effect and mechanism of amentoflavone in combination with cisplatin in OSCC. We investigated the combination effect and mechanism of amentoflavone and cisplatin via cell viability analysis, flow cytometry-based apoptosis analyses, transwell migration/invasion assay, immunofluorescence staining and western blotting assay. Both amentoflavone and QNZ (NF-κB inhibitor) significantly increased cisplatin-induced cytotoxicity. Amentoflavone reduced cisplatin-triggered NF-κB activity and enhanced cisplatin-induced intrinsic caspase-dependent and independent apoptotic pathways. Moreover, amentoflavone augments cisplatin-suppressed invasion and migration ability of OSCC cells. Inactivation of NF-κB and induction of apoptosis through intrinsic caspase-dependent and independent apoptotic pathways are associated with amentoflavone enhanced anti-OSCC efficacy of cisplatin.

Emerging connectivity of programmed cell death pathways and its physiological implications.

The removal of functionally dispensable, infected or potentially neoplastic cells is driven by programmed cell death (PCD) pathways, highlighting their important roles in homeostasis, host defence against pathogens, cancer and a range of other pathologies. Several types of PCD pathways have been described, including apoptosis, necroptosis and pyroptosis; they employ distinct molecular and cellular processes and differ in their outcomes, such as the capacity to trigger inflammatory responses. Recent genetic and biochemical studies have revealed remarkable flexibility in the use of these PCD pathways and indicate a considerable degree of plasticity in their molecular regulation; for example, despite having a primary role in inducing pyroptosis, inflammatory caspases can also induce apoptosis, and conversely, apoptotic stimuli can trigger pyroptosis. Intriguingly, this flexibility is most pronounced in cellular responses to infection, while apoptosis is the dominant cell death process through which organisms prevent the development of cancer. In this Review, we summarize the mechanisms of the different types of PCD and describe the physiological and pathological processes that engage crosstalk between these pathways, focusing on infections and cancer. We discuss the intriguing notion that the different types of PCD could be seen as a single, coordinated cell death system, in which the individual pathways are highly interconnected and can flexibly compensate for one another.

The role of PIK3CA mutations in the development of breast cancer (a literature review)

Today, breast cancer occupies a leading position in the structure of morbidity and mortality among women in Ukraineand and throughout the world. Late diagnosis of the disease adversely affects the prognosis. Since this pathology is characterized by a wide range of gene mutations, the relationship between the molecular genetic characteristics of a tumor and the prognostic and clinical characteristics of breast cancer is an extremely important issue. The PI3K/Akt signaling cascade is one of the key intracellular signaling pathways associated with the control of cell proliferation and regulation of potential oncogene protein kinase B/Akt functions. It can suppress apoptosis in different types of cancer, contributing to tumor cells survival. Also, mutations and amplification of the PI3K/Akt cascade components cause malignant cell transformation of various origin. The PIK3CA gene is one of the oncogenes, somatic mutations in which play an important role in the pathogenesis and progression of breast cancer. It encodes p110-α, the catalytic subunit of phosphatidylinositol-3-kinase-α. The most frequent mutation in PIK3CA gene is H1047R. Conclusions. Numerous studies have shown that PIK3CA gene mutations in breast cancer patients have the potential to become a clinically important biomarker for improving the disease diagnosis and developing individualized targeted therapy. In this literature review we discuss the molecular mechanisms of PI3K signaling cascade activation and the role of PIK3CA mutations in the development of breast cancer.

Apigenin as an anticancer agent.

Apigenin is an edible plant-derived flavonoid that has been reported as an anticancer agent in several experimental and biological studies. It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways. Apigenin induces apoptosis by the activation of extrinsic caspase-dependent pathway by upregulating the mRNA expressions of caspase-3, caspase-8, and TNF-α. It induces intrinsic apoptosis pathway as evidenced by the induction of cytochrome c, Bax, and caspase-3, while caspase-8, TNF-α, and B-cell lymphoma 2 levels remained unchanged in human prostate cancer PC-3 cells. Apigenin treatment leads to significant downregulation of matrix metallopeptidases-2, -9, Snail, and Slug, suppressing invasion. The expressions of NF-κB p105/p50, PI3K, Akt, and the phosphorylation of p-Akt decreases after treatment with apigenin. However, apigenin-mediated treatment significantly reduces pluripotency marker Oct3/4 protein expression which might be associated with the downregulation of PI3K/Akt/NF-κB signaling.

Possible applications of salvianolic acid B against different cancers

Cancer is the second death causing disease worldwide after cardiovascular abnormalities. The difficulty in treating tumor cells with more precise targeted interventions and recurrence of cancer after treatment may pose great difficulty in developing sustainable therapeutic regimens. These limitations have prompted the need to explore several compounds with ability to cease tumor growth while at the same time induce apoptosis of tumor cells. Several studies have emphasized the use of natural compounds as antitumor agents due to their high efficacy against cancer cells and low toxicity in normal cells. Salvianolic acid B (SAB), a naturally occurring phenolic compound extracted from the radix of Chinese herb Salvia miltiorrhiza can induce apoptosis in different types of tumor cells. It can be used to treat cardiovascular and neurodegenerative disorders, hepatic fibrosis, and cancers. Several studies have shown that SAB can mitigate tumorigenesis by modulating MAPK, PI3K/AKT, and NF-ĸB signaling pathways. It also sensitizes the tumor cells to different anti-cancer agents by reversing the multi-drug resistance mechanisms found in tumor cells. This review summarizes the studies showing antitumor potential of SAB in different types of cancer cell lines, animal models and highlights the possible mechanisms through which SAB can induce apoptosis, inhibit growth and metastasis in tumor cells. Moreover, the possible role of nano-technological approaches to induce targeted delivery of SAB to eradicate tumor cells has been also discussed.

Function of flavonoids on different types of programmed cell death and its mechanism: a review

Cell death in the living system plays a vital role in maintaining the homeostasis and balancing the cell count in the body. Programmed cell death (PCD) is a crucial component of several development and defense mechanisms. PCD is also important in terms of aging which avoids the accumulation of cellular damage by maintaining cell division. Depending on the execution of cell death and its role in destruction, PCD is categorized into several subtypes. The major different forms of PCD in animals are apoptosis, autophagy and necrosis, which can be distinct in morphological terms. More intense investigations of cell death have given close insight showing other important types of cellular destruction and their pivotal roles in treating disease conditions like cancer. Flavonoids have been acquired a great interest for disease therapies and chemoprevention through activation of several PCD mechanisms. The significant potential of natural flavonoids in the induction of distinct signaling cascades is being a massive approach for targeting uncontrolled cell growth. For these reasons, understanding PCD mechanisms is a promising approach for the interventions in treating cancer. Thus, it is intriguing that understanding the different forms of PCD mechanism induced by flavonoids with more accurate descriptions on the biochemical and cellular processes are gaining more significance in cancer research. Here, we provide a brief overview on the different types of PCD and aim to discuss the functional role of flavonoids in promoting different types of cell death as well as an extensive brief review on their mechanism of action has been highlighted.

Pro-apoptotic genes as new targets for single and combinatorial treatments with resveratrol and curcumin in colorectal cancer.

Colorectal cancer (CRC) represents the third most diagnosed type of cancer worldwide with high mortality and an increased incidence rate. Bioactive dietary components such as curcumin and resveratrol have great therapeutic potential as they can modulate a plethora of signaling pathways related to colorectal carcinogenesis. Previous data have demonstrated that curcumin and resveratrol can induce apoptosis in different types of cancer cells. Considering the lack of data on the combinatorial effect of curcumin and resveratrol associated with the induction of apoptosis in colorectal pathology, the main objective of this study is to investigate the impact of single vs. combinatorial treatment of resveratrol and curcumin on their cytotoxic effects, as well as the modulation of several essential pro-apoptotic genes, on two colorectal cancer cell lines (DLD-1 and Caco-2) different in terms of chromosomal stability (MSI and MSS). The cytotoxic effects were evaluated by the MTT assay, the nature of the interaction between curcumin and resveratrol was assessed by the combination index method and the expression levels of key genes involved in the modulation of pro-apoptotic mechanisms were evaluated by RT-qPCR. Our data indicate that the combination treatment of curcumin and resveratrol is more effective in inhibiting the proliferation in a dose-dependent manner, with a synergistic effect for the DLD-1 cell line (CI < 1) and an additive effect for the Caco-2 cell line (CI ≥ 1). The IC50 values for the combination treatment were 71.8 μM (20.5 μM curcumin + 51.3 μM resveratrol) for the DLD-1 cell line and 66.21 μM (18.9 μM curcumin + 47.3 μM resveratrol) for the Caco-2 cell line, respectively. Our data pointed out, for the first time, that several genes involved in the modulation of apoptosis, including PMAIP1, BID, ZMAT3, CASP3, CASP7, and FAS, represent new targets of both singular and combinatorial treatments with resveratrol and curcumin, and also the combinatorial approach of curcumin and resveratrol exhibits a more powerful gene regulating effect compared to single treatment. Considering the beneficial aspects of the combinatorial approach with curcumin and resveratrol on colorectal cancer cells further studies should address the possible pharmacological benefits of using a combination of both dietary agents with different chemotherapeutic drug approaches.