Abstract
Colorectal cancer (CRC) is one of the intimidating causes of death around the world. CRC originated from mutations of tumor suppressor genes, proto-oncogenes and DNA repair genes. Though platinum (Pt)-based anticancer drugs have been widely used in the treatment of cancer, their toxicity and CRC cells’ resistance to Pt drugs has piqued interest in the search for alternative metal-based drugs. Ruthenium (Ru)-based compounds displayed promising anticancer activity due to their unique chemical properties. Ru-complexes are reported to exert their anticancer activities in CRC cells by regulating different cell signaling pathways that are either directly or indirectly associated with cell growth, division, proliferation, and migration. Additionally, some Ru-based drug candidates showed higher potency compared to commercially available Pt-based anticancer drugs in CRC cell line models. Meanwhile Ru nanoparticles coupled with photosensitizers or anticancer agents have also shown theranostic potential towards CRC. Ru-nanoformulations improve drug efficacy, targeted drug delivery, immune activation, and biocompatibility, and therefore may be capable of overcoming some of the existing chemotherapeutic limitations. Among the potential Ru-based compounds, only Ru (III)-based drug NKP-1339 has undergone phase-Ib clinical trials in CRC treatment.
Highlights
Among the Pt-based drugs, only Oxaliplatin is approved by Food and Drug Administration (FDA) in Colorectal cancer (CRC) treatment
Decreased expression of Hypoxia-inducible factor-1 (HIF-1) protein level affects in downregulating HIF-1 target genes including vascular endothelial growth factor (VEGF) which modulate tumor angiogenesis [153,155], glucose transporter 1 (GLUT1) that mediate glucose uptake [156], and alpha-enolase (ENO1) which is crucial for glucose metabolism acting as a key catalyzing enzyme in the glycolysis (Figure 3→XI) [157]
Many Ru-complexes were found to be more efficient than the Ptbased drugs; Ru could be used as an alternative to Pt-based drugs
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Colorectal cancer (CRC) is a type of malignant neoplasm of the colon or rectum epithelial cell lining [1,2], which is recognized as the third most prevalent cancer worldwide and is the fourth leading cause of death [3,4] It accounts for about 10% of all yearly diagnosed cancers and cancer-related deaths globally [5]. OXA has severe side effects [20] and drug resistance [21] Such limitations inspire the search for alternative metal-based anticancer drugs. Among the Pt-based drugs, only Oxaliplatin is approved by FDA in CRC treatment. To overcome the limitation of Pt-drugs, Ru-complexes could be used as an alternative to Pt-based chemotherapeutic drugs in CRC. The molecular mechanism of action(s) such as effects on nucleic acids, cell proliferative pathways, and cell cycle are summarized and compared their efficiency with Pt-based drugs and other chemotherapeutic drugs i.e., 5-Fluorouracil (5-FLU), Doxorubicin (DOX), and Etoposide (ETP)
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