Inhibitory effects of indirubin‐3′‐monoxime against human osteosarcoma

Abstract

Indirubin is widely used as the active component of “Dangui Luhui Wan” in ancient China. However, its effects against the osteosarcoma (OS), the most common primary malignancy, are still unknown. In our present study, we investigated the effects of the Indirubin‐3′‐monoxime (I3M), a derivative of indirubin with better water solubility, against the OS cells. We found I3M inhibited OS cell proliferation in a dose‐dependent manner. Flow cytometry assays showed that I3M could not only induce OS cell apoptosis in a time‐ and dose‐dependent manner but also regulate the cell cycle distribution. Additionally, we demonstrated that several Bcl‐2 family members, cyclin‐dependent kinases (CDKs) and cyclins contributed to this process. Furthermore, out data verified that I3M suppressed OS cell migration and invasion by decreasing MMP‐2 and MMP‐9 levels. Moreover, survivin and focal adhesion kinase (FAK) might play important roles in the anti‐OS effects of I3M. The administration of I3M also inhibited the OS cell growth in mice. Taken together, our results indicated the inhibitory effects of I3M against human OS and thus might be an efficient candidate for OS chemotherapy.

Indirubin in Vitro Apoptotic Effect Towards Chronic Lymphocytic Leukaemia (CLL) Lineage

“…we provided evidences that I3M exerts apoptotic effects on the CLL cells by decreasing Bcl-2 expression [23,27]. An increase in Bax expression was reported by Li et al in glioma cells [23].…”

“…These compounds are known to have some therapeutic effects, however rarely the same have been tested in scienti cally studies. Indirubin-3monoxime (I3M) is described to be a potent inducer of apoptotic cell death in a wide spectrum of human cancer cells with few cytotoxicity on normal cells, including breast cancer, acute lymphoblastic leukemia, chronic myelomonocytic leukemia, osteosarcoma, and neuroblastoma [27][28][29]. However, the exact mechanisms underlying the apoptotic cell death induced by I3M have not been fully elucidated.…”

Synergistic effect of plasma-activated medium and novel indirubin derivatives on human skin cancer cells by activation of the AhR pathway

“…In addition, it has an enhanced anti-proliferative and pro-apoptotic effect. Regarding the metastatic potential of cancer, I3M led to decreased cell migration and invasion 13 , 30 , 31 . The inhibitory effect of I3M on tumour proliferation has also been studied in vivo.…”

“…However, indirubin promotes the expression of the thrombopoietin receptor, a transmembrane protein, in peripheral blood mononuclear cells 41 . The structure of the cell membrane and extracellular matrix could also be altered via mechanisms that influence cancer cell migration and invasion 31 , with implications for impedance measurement and hence adhesion capacity values.…”

Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential

“…Among the synthetic indirubin analogs, indirubin-3′-monoxime (compound 1 ) has been reported to inhibit growth of human MCF-7 breast cancer cells [ 124 , 125 ], osteosarcoma [ 82 ], and cholangiocarcinoma cells [ 81 ]. Compound 1 also suppressed the production of interleukin (IL)-1β, IL-6, NO, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) expression via downregulation of NF-κB and JNK signaling pathways in lipopolysaccharide (LPS)-treated murine RAW264.7 macrophage cells [ 112 ].…”