## 5 Conclusions  
Intrinsic (de novo) or acquired tumor cell resistance remains a major challenge for different types of chemotherapeutical approaches. Despite the recent advances in surgery, radiotherapy, and especially in chemotherapy that have led to major achievements in cancer treatment, the development of tumor cell resistance to chemotherapeutic agents is still an important problem, reducing the effectiveness of available therapies. A major goal of early approaches in individualized therapy was to develop in vitro tests to predict tumors' drug responsiveness. Since the chemosensitivity of tumors could not be predicted with high reliability, the evaluation of drug resistance is reliable independent of tumor type, test assay, and drug used in in vitro tests [72; 73]. One of the most effective anticancer agents used to treat colon cancer is the platinum-based drugs, such as cisplatin, oxaliplatin, or carboplatin, but the insurgence of drug resistance and the high systemic toxicity developed are among the important obstacles against the success of chemotherapy. Ruthenium compounds have drawn great attention for their potential clinical application as anticancer drugs. Contrast data are available on their anticancer effects in colon cancer. The emerging interest appeared in developing new pharmaceutical compounds, such as Ru(III) complexes, with a high potential for chemotherapeutic use in cancer, and the improvement in their delivery prompted us to investigate their role in the modulation of colon cell proliferation vs. cytotoxicity, induction of apoptosis, and cell cycle regulation, in order to further find ways to improve their biological effects. The Ru(III) complexes with quinolones developed by our group manifested a strong drug-mediated cytotoxicity against the LoVo colon cancer cell line, as assessed both by real-time cell analysis (RTCA) or end-point cytotoxicity assay, and results varied depending on the compound and concentration used. The registered RTCA proliferation curves of treated LoVo cells and the calculated IC50 values showed that Ru(III)-nf, -oflo, -levo, and -cipro were the most effective in killing colon cells at lower doses. Their toxicity profiles seemed to be lower compared to cisplatin; therefore, a wide modulation of concentrations might be further used in therapeutic approaches, and the control of non-target cell-toxicity could be improved. Since apoptosis started to be considered as an ideal way to eliminate precancerous and/or cancer cells, and chemopreverity agents might modulate apoptosis, our experimental results obtained after evaluation of the apoptotic events induced by Ru(III) complexes with quinolones showed that treatments of colon cancer cells with the drugs under study induced dose-dependent effects, which could be useful in the management and therapy of cancer, since they proved to be at least as efficient as cisplatin. Treatments with 10 uM of all Ru(III) complexes with quinolones induced over 32% of apoptosis, while Ru-cipro, Ru-pip, Ru-enoxa, and Ru-enro induced higher levels of apoptotic events than CisPt. When drug doses of cell treatments were increased to 50 uM, stronger effects were observed both for Ru(III) complexes and CisPt treatments, the highest apoptosis being induced by Ru-enoxa treatment (73.34% apoptotic events). Ru(III) complexes with quinolones seemed also to regulate the colon cell proliferation through cell cycle phases in a dose-dependent manner: both 10 and 50 uM treatments induced a decrease in the cells found in the synthesis (S) phase; in addition, we observed an increase in the cell cycle arrest mainly in the G0/G1 phase, the highest effect being obtained for Ru-pip, Ru-nf, Ru-oflo, Ru-enro, and Ru-enoxa treated cells. Our results, consistent with other scientific reports highlighting the cytotoxic effects of ruthenium-based drugs in colon cells, showed that Ru(III) complexes with quinolone antibiotics might be further used to elaborate new therapeutic approaches for future personalized cancer treatments. Conceptualization, M.M. and V.U.