NV-128 blocks OCSC differentiation

Data presented at the annual meeting of the American Association for Cancer Research, in Colorado, show that NV-128, a synthetic isoflavonoid  compound developed by US firm Novogen, not only induces cell death in  ovarian cancer stem cells, but also blocks their differentiation into  structures that are required to support tumor growth.

Novogen said that the anti-proliferative effects were achieved as a  result of NV-128 inhibiting phosphorylation of the pro-survival mTOR  pathway resulting in mitochondrial depolarization and cell death. Time  lapsed photographic morphometry revealed in graphic detail how NV-128  induces morphological changes in OCSCs after 24 hours, even when dosed  as low as 1mcg/ml with a progressive clearing of cytoplasm and  condensation of nuclear material.

The effect of NV-128 on OCSC vessel formation was observed by plating  OCSCs in high-density matrigel either without NV-128 or in the presence  of 0.1mg/ml NV-128 and observing for 48 hours. Whereas the control  cultures showed differentiation of the stem cells into endothelial-type  cells forming structurally intact blood vessels in the culture plates,  cells cultured in the presence of NV-128 showed no differentiation and  no structural elements were observed, the firm noted. OCSCs represent a  highly chemo-resistant cell population, allowing them to survive  conventional chemotherapy.