Cancer is currently among the leading causes of mortality globally. Colorectal cancer (CRC) ranks second among the most common types of cancer in terms of mortality worldwide. This type of cancer arises from mutations in the colonic and rectal epithelial tissues that target oncogenes, tumor suppressor genes and genes related to DNA repair mechanisms. The aim of the present review was to provide an explanation of CRC classification, which is carried out according to the histological subtype, location and molecular pathways implicated in its development. The pathogenic mechanisms implicated in CRC may involve one of three different molecular pathways: Chromosomal instability, microsatellite instability and cytosine preceding guanine island methylator phenotype. In addition, a variety of mutated genes associated with CRC, which affect certain signaling pathways, including DNA mismatch repair, cell cycle checkpoints and apoptotic pathways, were discussed. Moreover, a brief description of the risk factors and the symptoms associated with CRC was also provided. Finally, the treatment approaches to CRC were outlined.

Although 5‑fluorouracil (5‑FU)‑based chemotherapy is the major treatment for colorectal cancer, it has disadvantages such as systemic toxicity, lack of effectiveness and selectivity, and development of resistance. Capecitabine, a prodrug form of 5‑FU, was designed to overcome these drawbacks, to fulfill the need for more convenient therapy, and to improve safety, tolerability and intratumor drug concentration levels through a tumor‑specific conversion to the active 5‑FU drug. The purpose of the present review is to provide a comprehensive comparison between 5‑FU therapy and capecitabine. In the current review, anticancer drug classification was discussed and the development of capecitabine from the original fluorinated analogue (5‑FU) to overcome its drawbacks was explained. Specifically, 5‑FU is compared with capecitabine therapy regarding various properties, including drug metabolism, cellular mechanism, effect on the apoptosis pathway and cell cycle phases, safety and tolerability. Moreover, three metabolizing enzymes required for the activation of capecitabine to 5‑FU were discussed. Capecitabine, as monotherapy or in combination with other chemotherapies, exhibited improved drug efficacy and survival. However, the changes that mediate the chemoresistance of capecitabine treatment were classified as intracellular, extracellular or cell surface factors, or cell‑phenotype state. Future studies should examine the efficacy of capecitabine combined with novel and safe drugs other than chemotherapeutic agents that play a role in the inhibition of tumor initiation, progression and metastasis.

Zamzam water is naturally alkaline and rich in a variety of minerals which may represent a powerful tool for cancer therapy. In this research, the cytotoxic effects of Zamzam water were investigated in human lung cancer (A549) cell line and compared with human skin fibroblasts (HSF). Two different preparations of Zamzam water were used: Z1, with pH adjusted to 7.2 and Z2, with no pH adjustment. The effects of both treatments on the morphology of the A549 and HSF cell lines were investigated. The cell viability of HSF and A549 cells was identified by the MTT assay and trypan blue exclusion. Detection of apoptotic cells and cell cycle analyses were determined using flow cytometry. Moreover, reactive oxygen species (ROS) were measured for both cell lines. Both Zamzam water treatments, Z1 and Z2 showed reductions in the cell viability of A549 cells. Cell death occurred via necrosis among cells treated with Z2. Cell cycle arrest occurred in the G0/G1 phases for cells treated with Z2. Cellular and mitochondrial ROS productions were not affected by either treatment. Our findings indicate that Zamzam water might have potential therapeutic efficacy for lung cancer.

Zamzam water (ZW) is a naturally hard alkaline type of water with unique physical and chemical properties that are different from any other water. The aim of the current work is to evaluate the potential anticancer activity of ZW against colon cancer. Human colon cancer HCT-116 and human skin fibroblast HSF cell lines were treated with two treatment conditions of ZW, Z1 with adjusted pH to 7.4 and Z2 without pH adjustment (pH 8). Cell viability was assessed using MTT and trypan blue dye exclusion assays. Cell cycle alterations and the type of cell death were investigated using flow cytometry technique. Cellular and mitochondrial reactive oxygen species (ROS) levels were quantified by H2DCFDA and MitoSOX assays, respectively. The results of the current study showed that both ZW treatments reduced cell viability of cancer cells. MTT assay showed a significant reduction in cell viability to 87% and 66%, respectively, after treatment with Z1 and Z2 (p≤0.0001). Cell death has occurred via apoptotic pathway under the two treatment conditions. The percentage of early apoptosis was 3%, 3.5% and 2.8% in control, Z1 and Z2 respectively. In the late apoptotic stage, there was a significant increase (4.2%) only for Z2 treatment in comparison to the control (p≤0.001). The cells were arrested in the G2/M phase of the cell cycle, and decreased in G1 phase after 24 hours of treatment with ZW. Only Z2 treatment, showed an increase in the production of both cytoplasmic and mitochondrial ROS. In conclusion, our results indicate, for the first time, that ZW induces apoptosis of human colon cancer HCT-116 cells, suggesting the potential anticancer effect of ZW against colon cancer.

Background: Zamzam water (ZW) is a natural alkaline water that contains several minerals that may represent a powerful tool for cancer therapy. Objectives: In this research, in vitro antiproliferative and apoptotic effects of ZW were investigated in the human breast cancer cell line MCF-7. Materials and Methods: This study was conducted between January 2015 and February 2016. The effects of ZW on the morphology and the cell viability of human breast cancer cell line MCF-7 were determined. The cell death type and cell cycle changes were investigated using flow cytometry. Finally, reactive oxygen species (ROS) were also measured by fluorometric technique. Results: MCF-7 cells treated with either ZW with adjusted pH at 7.2 or unadjusted pH at 8 showed reduced cell viability of cancerous cells. The cell death occurred through the apoptosis pathway under both treatment conditions. The treated MCF-7 cells were arrested in the G2/M phase and decreased in the G1 phase. Only the unadjusted pH ZW sample demonstrated an increase in the production of both cytoplasmic and mitochondrial ROS in MCF-7 cells. Conclusion: All the results in the present study indicated, for the first time, that ZW might have anticancer and apoptotic effects on breast cancer cell line.

Background/Objectives: Colorectal cancer (CRC) is a significant global health issue with rising incidence and mortality rates. In oncology, drug repurposing has emerged as a promising therapeutic strategy in conjunction with conventional treatments. This study aimed to evaluate the potential of repurposing propranolol (PRO), a beta blocker, for the treatment of CRC cell lines (HCT-116 and HT-29), both as a monotherapy and in combination with capecitabine (CAP). Methods: Effects of mono- and combination therapies on viability, combination index, morphology, and cell death induction of CRC cells were assessed. Transcriptome analysis of HT-29 cells was performed using RNA sequencing. Metabolite profiling was conducted, and changes in biochemical parameters were evaluated using flow cytometry and biochemical analyses. Results: The combination index showed that HT-29 cells were the most responsive to the combined treatment, even with PIK3CA, B-RAF (V600E), and TP53 mutations. Moreover, ferroptosis was synergistically activated in the combined group of HT-29 in comparison to control. Furthermore, we observed an increase in OXPHOS metabolites, along with elevated intracellular and mitochondrial ROS, disruption of mitochondrial membrane potential, and greater levels of malondialdehyde (MDA) in the HT-29 combined group, which are the features of ferroptosis. Furthermore, ferroptosis induction was coupled with necroptosis, as indicated by RNA-sequencing data. Combination therapy inhibited cell migration and enhanced the immune response of HT-29 cells. Conclusions: These findings suggest that PRO is promising as a potential adjuvant therapy in combination with CAP for the treatment of CRC. Only HT-29 cells with the B-RAF (V600E) mutation showed promising findings in this study.