Colorectal cancer is the third most common cancer worldwide with a high mortality rate at the advanced stages. However, colorectal cancer is not a single type of tumor; its pathogenesis depends on the anatomical location of the tumor and differs between right side and left side of the colon. Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. Therapy responses are totally different between these tumor entities. Left-sided colorectal cancer (LCRC) patients benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based regimes, and targeted therapies such as anti- epidermal growth factor receptor (EGFR) therapy, and have a better prognosis. Right-sided colorectal cancer (RCRC) patients do not respond well to conventional chemotherapies, but demonstrate more promising results with immunotherapies because these tumors have high antigenic load. For the development of effective therapy regimes and better treatment options, it is essential to evaluate right-sided and left-sided tumors as separate entities, and design the therapy regime considering the differences between these tumors.

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Halophila stipulacea is a well-known invasive marine sea grass in the Mediterranean Sea. Having been introduced into the Mediterranean Sea via the Suez Channel, it is considered a Lessepsian migrant. Although, unlike other invasive marine seaweeds, it has not demonstrated serious negative impacts on indigenous species, it does have remarkable invasive properties. The present in-silico study reveals the biotechnological features of H. stipulacea by showing bioactive peptides from its rubisc/o protein. These are features such as antioxidant and hypolipideamic activities, dipeptidyl peptidase-IV and angiotensin converting enzyme inhibitions. The reported data open up new applications for such bioactive peptides in the field of pharmacy, medicine and also the food industry.

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Colorectal cancer (CRC) is the third most common cancer in the world and third leading cause of cancer-related deaths in men and women as well. While early screening procedures and removal of small polyps improve the survival rates among the patients, there is still need for new diagnostic and therapeutic approaches for developing more effective treatments. MicroRNAs (miRNAs) are short noncoding RNA fragments, which involve in posttranscriptional regulation of gene expression, and they are shown to involve in tumorigenesis either targeting oncogenes or tumor suppressor genes. Based on the current studies, miRNAs are now suggested as potential biomarkers for CRC diagnosis, prognosis, and therapeutic responses. In this chapter, the latest findings on the role of miRNA in CRC in many aspects are reviewed: diagnosis (role of circular miRNAs in blood and miRNAs from tissue biopsies and their potential role in pathophysiology and diagnosis of CRC), prognosis (miRNAs related with metastasis, recurrence, and survival rates in CRC), and therapeutic responses (role of miRNAs both in chemotherapies and/or in targeted therapies in CRC). In conclusion, miRNAs are promising molecules for diagnosis, prognosis, and therapeutic responses of CRC.

Background The aim of the study was in-silico drug-likeness analysis, absorption, distribution, metabolism, and excretion (ADME) properties, and molecular docking studies of anthocyanins as natural anticancer compounds against acting receptor-like kinase 5 (ALK5) receptor. Transforming growth factor-β (TGF-β) plays an essential role in various cellular processes. Increased expression of TGF-β and its receptor TGFβR-I (i.e. ALK5) have been associated with poor prognosis in cancer patients. Methods The drug-likeness activity of anthocyanins was performed using SwissADME tool. Molecular docking studies were carried out by using the Autodock Vina 1.5.6 tool. Results The results revealed that cyanidin-3-arabinoside (C3A), pelargonidin-3-glucoside (P3G), and peonidin-3-arabinoside (P3A) were able to use both Lipinski’s rule of five and Ghose variations. The binding energies of C3A, P3G, and P3A against ALK5 were found as −8.0, −8.3, and −8.4 kcal mol−1, respectively. Conclusion These selected anthocyanins have shown higher binding energies than known inhibitors to the ALK5 receptor. Further in-vitro and in-vivo studies were strongly recommended to clarify the whole mechanism.

Biological invasion is the successful spread and establishment of a species in a novel environment that adversely affects the biodiversity, ecology, and economy. Both invasive and non-invasive species of the Caulerpa genus secrete more than thirty different secondary metabolites. Caulerpin is one of the most common secondary metabolites in genus Caulerpa. In this study, caulerpin found in invasive Caulerpa cylindracea and non-invasive Caulerpa lentillifera extracts were analyzed, quantified, and compared using high-performance thin layer chromatography (HPTLC) for the first time. The anticancer activities of caulerpin against HCT-116 and HT-29 colorectal cancer (CRC) cell lines were also tested. Caulerpin levels were found higher in the invasive form (108.83 ± 5.07 µg mL−1 and 96.49 ± 4.54 µg mL−1). Furthermore, caulerpin isolated from invasive Caulerpa decreased cell viability in a concentration-dependent manner (IC50 values were found between 119 and 179 µM), inhibited invasion-migration, and induced apoptosis in CRC cells. In comparison, no cytotoxic effects on the normal cell lines (HDF and NIH-3T3) were observed. In conclusion, HPTLC is a quick and novel method to investigate the caulerpin levels found in Caulerpa extracts, and this paper proposes an alternative utilization method for invasive C. cylindracea due to significant caulerpin content compared to non-invasive C. lentillifera.

Caulerpa spp. secrete more than thirty different bioactive chemicals which have already been used in cancer treatment research since they play a pivotal role in cancer metabolism. Colorectal cancer is one of the most common cancer types, thus using novel and effective chemicals for colorectal cancer treatment is crucial. In the cheminformatics pipeline of this study, ADME-Tox and drug-likeness tests were performed for filtering the secondary metabolites of Caulerpa spp. The ligands which were selected from the ADME test were used for in silico molecular docking studies against the enzymes of the oxidative branch of the pentose phosphate pathway (glucose-6-phosphate dehydrogenase and 6-phosphoglutarate dehydrogenase), which is of great importance for colorectal cancer, by using AutoDock Vina. Pharmacophore modeling was carried out to align the molecules. Molecular dynamic simulations were performed for each target to validate the molecular docking studies and binding free energies were calculated. According to the ADME test results, 13 different secondary metabolites were selected as potential ligands. Molecular docking studies revealed that vina scores of caulerpin and monomethyl caulerpinate for G6PDH were found as −10.6 kcal mol-1, −10.5 kcal mol-1, respectively. Also, the vina score of caulersin for 6PGD was found as −10.7 kcal mol-1. The highest and the lowest binding free energies were calculated for monomethyl caulerpinate and caulersin, respectively. This in silico study showed that caulerpin, monomethyl caulerpinate, and caulersin could be evaluated as promising marine phytochemicals against pentose phosphate pathway enzymes and further studies are recommended to investigate the detailed activity of these secondary metabolites on these targets.