The natural compound Alizarin as an osteotropic drug for the treatment of bone tumors

Abstract

Despite significant clinical improvements, conventional therapies for bone cancer treatment are limited by significant systemic toxicity and lack of specific targeting. In this study, we considered Alizarin, a natural hydroxyanthraquinone derived from madder root with high affinity to calcium and remarkable osteotropic features, as a novel approach for bone cancer treatment. Due to its antitumor properties, as demostrated in colon cancer cells, and to its tropism to bone, Alizarin may be an ideal drug to reduce bone tumor growth. We demonstrated that low dosages of Alizarin strongly inhibited the osteosarcoma (IC 50 for Saos-2, MG-63, and U-2 OS cells, 27.5, 29.0, and 69.9 mg/ml, respectively) and breast carcinoma (IC 50 for MDA-MB-231 cells, 62.1 mg/ml) cell proliferation in vitro. Importantly, Alizarin had a significantly lower inhibitory activity on normal cells (IC 50 for MSC, 828.6 mg/ml), thereby revealing a selective activity towards malignant cells. Furthermore, we found that Alizarin acted through the inhibition of ERK phosphorylation and cell cycle arrest in the S-phase. Finally, Alizarin significantly and strongly impaired both osteosarcoma and breast cancer tumorigenesis. Our results highlight a selective and effective inhibitory activity of Alizarin towards cancerous cells, laying the basis for further studies to investigate its application in bone cancer therapy.

Flavokawain B, a kava chalcone, inhibits growth of human osteosarcoma cells through G2/M cell cycle arrest and apoptosis

“…Although maximal dose escalation of conventional chemotherapy has been utilized, there is still no significant gain in clinical outcome. The use of conventional antitumor drugs, such as doxorubicin and methotrexate, is usually limited due to their systemic toxicity and lack of specificity [19]. Furthermore, no effective standard second-line chemotherapeutic agent has been identified in local or distant relapsed osteosarcoma.…”

Microbial Transformation of Bioactive Anthraquinones ? A Review

“…Alizarin 7 was found to have a better antioxidant activity when compared with green tea polyphenol and vitamin E 35 . In additional, alizarin (7) also showed good cytotoxicity against osteosarcoma and breast carcinoma cells 36 . It also exhibits immunosuppressive activity 37 .…”

Comprehensive analysis of the atenolol – DNA complex by viscometric, molecular docking and spectroscopic techniques

“…Alizarin (ALZ) is a red, natural, non‐toxic hydroxyanthraquinone drug derived from the madder root that has been mainly used for dying fabrics, or as a staining reagent to stain murine cartilage and bone . Caterina Fotia and co‐workers reported that ALZ can be used in the treatment of bone marrow tumors . In the present study, for the first time, we report the use of ALZ as a spectroscopic probe for the interaction of the neutral drug, ATN, with DNA.…”

“…[34] Caterina Fotia and co-workers reported that ALZ can be used in the treatment of bone marrow tumors. [35] In the present study, for the first time, we report the use of ALZ as a spectroscopic probe for the interaction of the neutral drug, ATN, with DNA.…”