Natural compound from an Indian plant could help against mesothelioma; Research

Withania somniferaResearchers have found that a natural compound found in the medicinal plant Withania somnifera could be helpful against malignant pleural mesothelioma.

This research has been published online in the August 17th issue of the journal PLoS ONE.

Researchers already knew that Withania somnifera (also known as “Ashwagandha”, or “Indian ginseng”), which is a medicinal plant used in Indian Ayurvedic Medicine for centuries, has a bioactive compound Withaferin A (WA) that is helpful against inflammation, angiogenesis, and cancer. In this research, they worked in-vivo on the mouse model and in-vitro on the patient-derived cells of malignant pleural mesothelioma. Researchers found that WA not only stops proteasome activity but also increases apoptosis in malignant pleural mesothelioma. Proteasome is a protein complex involved in the degradation of the damaged proteins. In cancerous cells, inhibition of proteasome activity helps in the damage of cells. Apoptosis means the programmed cell death.

You can read the abstract of the paper here,

The medicinal plant Withania somnifera has been used for over centuries in Indian Ayurvedic Medicine to treat a wide spectrum of disorders. Withaferin A (WA), a bioactive compound that is isolated from this plant, has anti-inflammatory, immuno-modulatory, anti-angiogenic, and anti-cancer properties. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of WA and the molecular mechanisms involved. WA inhibited growth of the murine as well as patient-derived MPM cells in part by decreasing the chymotryptic activity of the proteasome that resulted in increased levels of ubiquitinated proteins and pro-apoptotic proteasome target proteins (p21, Bax, IκBα). WA suppression of MPM growth also involved elevated apoptosis as evidenced by activation of pro-apoptotic p38 stress activated protein kinase (SAPK) and caspase-3, elevated levels of pro-apoptotic Bax protein and cleavage of poly-(ADP-ribose)-polymerase (PARP). Our studies including gene-array based analyses further revealed that WA suppressed a number of cell growth and metastasis-promoting genes including c-myc. WA treatments also stimulated expression of the cell cycle and apoptosis regulatory protein (CARP)-1/CCAR1, a novel transducer of cell growth signaling. Knock-down of CARP-1, on the other hand, interfered with MPM growth inhibitory effects of WA. Intra-peritoneal administration of 5 mg/kg WA daily inhibited growth of murine MPM cell-derived tumors in vivo in part by inhibiting proteasome activity and stimulating apoptosis. Together our in vitro and in vivo studies suggest that WA suppresses MPM growth by targeting multiple pathways that include blockage of proteasome activity and stimulation of apoptosis, and thus holds promise as an anti-MPM agent.

Reference:

Yang H, Wang Y, Cheryan VT, Wu W, Cui CQ, et al. (2012) Withaferin A Inhibits the Proteasome Activity in Mesothelioma In Vitro and In Vivo. PLoS ONE, doi:10.1371/journal.pone.0041214

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