Ruthenium Complexes as Promising Candidates against Lung Cancer

Abstract

Lung cancer is one of the most common malignancies with the highest mortality rate and the second-highest incidence rate after breast cancer, posing a serious threat to human health. The accidental discovery of the antitumor properties of cisplatin in the early 1960s aroused a growing interest in metal-based compounds for cancer treatment. However, the clinical application of cisplatin is limited by serious side effects and drug resistance. Therefore, other transition metal complexes have been developed for the treatment of different malignant cancers. Among them, Ru(II/III)-based complexes have emerged as promising anticancer drug candidates due to their potential anticancer properties and selective cytotoxic activity. In this review, we summarized the latest developments of Ru(II/III) complexes against lung cancer, focusing mainly on the mechanisms of their biological activities, including induction of apoptosis, necroptosis, autophagy, cell cycle arrest, inhibition of cell proliferation, and invasion and metastasis of lung cancer cells.

The Anticancer Ruthenium Compound BOLD-100 Targets Glycolysis and Generates a Metabolic Vulnerability towards Glucose Deprivation

“…In sharp contrast to 2-DG, treatment with BOLD-100 resulted in decreased p62 and beclin-1 levels, pointing to an autophagy-promoting activity of the compound. These results are supported by previous studies reporting the induction of autophagy by ruthenium-based chemotherapy in different cancer types [82][83][84]. However, the strong increase, not only in LC3B II but also LC3B I levels especially in combination with 2-DG, raises doubts about whether BOLD-100-induced autophagy is indeed functional.…”

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

“…During recent decades, organometallic anticancer agents have emerged [4][5][6][7] as potential pharmaceutical options. More specifically, ruthenium compounds are considered the most promising drug candidates to date, because of their favorable kinetic properties, rich redox chemistry and high selectivity for cancer cells [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. In fact, several ruthenium complexes, such as the octahedral NAMI-A [23] or sodium trans-tetra-chloridobis(1Hindazole)ruthenate(III) (IT-139) [15,[24][25][26] complexes as well as arene-Ru(II) derivatives of the RAPTA family [27][28][29][30], containing the PTA ligand, or RM175 [31,32], have been complexes, such as the octahedral NAMI-A [23] or sodium trans-tetra-chloridobis(1Hdazole)ruthenate(III) (IT-139) [15,[24][25][26] complexes as well as arene-Ru(II) derivatives the RAPTA family [27][28][29][30], containing the PTA ligand, or RM175 [31,32], have been ev uated as chemotherapeutic agents in clinical trials (see Figure 1).…”

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

“…Given the number of Ru-based agents under preclinic development, however, it is expected that further candidates will move into clinical trials. From this perspective, there are many ruthenium complexes with intrinsic features and potential that, beyond question, deserve further development [ 90 , 97 , 98 , 111 , 112 ].…”