Gedunin – Cancer enemy from Indian plant

Gedunin has been isolated from the Indian neem tree (Credit: J. Med. Chem.)

Gedunin is a tetranortriterpenoid ingredient obtained from the Indian neem tree ( Azadirachta indica). It has been used as a natural remedy in Asia for centuries (Kamath SG et al., 2009). It has been used as antimalarial, insecticidal and anticancer in the recent times (Brandt GE et al., 2008).

This ingredient has anticancer activity and the mechanism of action has been found to be its inhibition of 90 kDa heat shock protein (Hsp90) (Brandt GE et al., 2008). Hsp90 plays an important role in helping the mutated proteins in cancer. Recently, researchers have found that gedunin binds directly to p23, i.e. helper protein of Hsp90, resulting in its inactivation. (Patwardhan CA et al., 2013).

Hsp90 is also an important regulator of androgen receptor. Thus, Hsp90 inhibitory activity of gedunin can work as a controlling strategy for androgen receptor activity in prostate cancer. (yi Lu et al., 2009)

Researchers found nearly 80% decrease in the cell proliferation in ovarian cancer cells after in-vitro treatment with gedunin (Kamath SG et al., 2009).

Reference:

Brandt GE, Schmidt MD, Prisinzano TE, Blagg BS, (2008). Gedunin, a novel hsp90 inhibitor: semisynthesis of derivatives and preliminary structure-activity relationships. Journal of Medicinal Chemistry, doi: 10.1021/jm8007486

Kamath SG, Chen N, Xiong Y, Wenham R, Apte S, Humphrey M, Cragun J, Lancaster JM, (2009). Gedunin, a novel natural substance, inhibits ovarian cancer cell proliferation. Int J Gynecol Cancer, doi: 10.1111/IGC.0b013e3181a83135

Patwardhan, C., Fauq, A., Peterson, L., Miller, C., Blagg, B., & Chadli, A. (2013). Gedunin Inactivates the Co-chaperone p23 Causing Cancer Cell Death by Apoptosis Journal of Biological Chemistry DOI: 10.1074/jbc.M112.427328

Yi Lu, Ram I. Mahato, (2009). Pharmaceutical Perspectives of Cancer Therapeutics. Springer.