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.
Highlights
(Ru2) (Figure 3) showed moderate antibacterial activity against Gram-positive and Gramnegative strains, but significantly high anticancer activity against non-small-cell lung cancer (NSCLC) cells (H1299). They exhibited high cytotoxicity to NSCLC cells with IC50 = 10–12.5 ± 0.5 and 15–20 ± 0.5 μg/mL, respectively, but low toxicity to human erythrocytes compared to cisplatin [48]
Like with NAMI-A, in vivo studies in 4T1 mammary carcithat theof occurrence and development of lung metastasis were suppressed significantly noma-bearing mice showed that the occurrence and development of lung metastasis were suppressed significantly and that no retinal toxicity or hepatotoxicity was found in mice after intraperitoneal injection of Ru9 and Ru10 at a dose of 17.5 mg/kg per day for consecutive 6 days, with three times in a 1-day interval
Since the high expression levels of BCL-2 and BCL-xL have been associated with cisplatin resistance and tumor recurrence in NSCLC patients [95], Ru31 may indirectly inhibit the resistance and relapse of lung cancer. [Ru(dmp)2](ClO4
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. A hematoporphyrin derivative, is the only PDT drug approved by the Food and Drug Administration for cancer therapy, including early and advanced lung cancer [28,29], extensive studies have been performed to develop novel Ru(II/III) complexes for efficient cancer treatment [16,18,30]. Several Ru(III) complexes that have entered clinical trials in different phases, such as KP1019 [36,37,38,39], KP-1339 [40], and NAMI-A [31,32,33,65], showed promising anticancer activity with limited side effects and have been used to prepare various derivatives
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