Cervical cancer
Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which inactivate the tumor suppressor protein p53 and pRb respectively. Withaferin A was found to down regulate expression of E6 and E7 oncoproteins, induce accumulation of p53, causes G2/M cell cycle arrest, alters the expression levels of apoptotic markers Bcl2, Bax and caspase3. In athymic mice model, withaferin reduced 70% of the tumor volume. Therefore, withaferin A can be a potential therapeutic agent for the treatment of cervical cancer without major side effects. Withaferin A has been shown to enhance radiation-induced apoptosis in certain cell lines. However, its mechanism of action on cell death is not well understood. It has been suggested that sensitization of cancer cells to radiation is due to the inhibition of NF-κB. It exhibits anti-tumor as well as anti-inflammatory activities. It can act as an immuno-suppressant by inhibiting NF-κB activation. In animal models, it prevented skin cancer induced by ultraviolet radiation. The antioxidant property of withaferin aid in the prevention of DNA damage by mutagens; in combination with detoxifying, anti-inflammatory and immunomodulatory effects, it can contribute to the chemopreventive action.