I read with great interest the recent article “Artesunate inhibits growth and induces apoptosis in human osteosarcoma HOS cell line in vitro and in vivo” by Xu et al. (2011), published in Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology). Artesunate exerts anti-neoplastic effects in a number of systemic malignancies besides osteosarcomas.
Artesunate exerts anti-proliferative effects in pulmonary adenocarcinomas. It mediates these anti-neoplastic effects by virtue of activating Bak (Zhou et al., 2012). At the same time, it down-regulates epidermal growth factor receptor expression. This results in augmented non-caspase dependent apoptosis in the adenocarcinoma cells. Artesunate mediated apoptosis is time as well as dose dependent. Interestingly, AIF and Bim play significant roles in this Bak-dependent accentuated apoptosis (Ma et al., 2011). Adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) expression is also attenuated while transcription of matrix metallopeptidase 7 (MMP-7) is also down-regulated (Zhao et al., 2011). In addition, arsenuate enhances the radio-sensitization of lung carcinoma cells. It mediates this effect by down-regulating cyclin B1 expression, resulting in augmented G2/M phase arrest (Rasheed et al., 2010).
Similarly, artesunate exhibits anti-neoplastic effects in breast carcinomas. Artesunate administration is typically accompanied by attenuated turnover as well as accentuated peri-nuclear localization of autophagosomes in the breast carcinoma cells. Mitochondrial outer membrane permeability is typically augmented. As a result, artesunate augments programmed cellular decline in breast carcinoma cells (Hamacher-Brady et al., 2011). Lysosomal iron plays a major role in the production of reactive oxygen species (ROS). Similarly, artesunate inhibits the PI3K/Akt signaling pathway in cervical malignancies. The expression of Bcl-xL is markedly attenuated. As a result, it accentuates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced intrinsic as well as extrinsic apoptosis in these cancers (Thanaketpaisarn et al., 2011). It also decreases TRAIL induced nuclear factor-κB (NF-κB) activity.
Artesunate also exerts anti-neoplastic effects in skin malignancies. It mediates these effects by up-regulating p21. At the same time it down-regulates cyclin D1 (Jiang et al., 2012). Cdk4 is also down-regulated simultaneously. As a consequence there is accentuated G0/G1 phase arrest. Artesunate also augments iron-dependent mitochondrial apoptosis. Similarly, artesunate enhances the radio-sensitivity of tumors such as gliomas. It mediates this effect by down-regulating the expression of surviving (Reichert et al., 2012). As a result, there is increased G2/M phase arrest. Intra-tumoral apoptosis is also markedly accentuated.
The above examples clearly illustrate the significant anti-proliferative and apoptosis enhancing effects of artesunate and the need for further large scale studies in this regard.
References
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