Natural Product Gossypol and its Derivatives in Precision Cancer Medicine

Abstract

Gossypol, a natural product extracted from the seed, roots, and stem of cotton, was initially used as a male contraceptive but was subsequently investigated as a novel antitumor agent. This review depicts the current status of gossypol and its derivatives as novel antitumor agents as well as presents their preparation and characteristics, especially of some gossypol Schiff bases, through quantitative and structural analyses. The main attractive target sites of gossypol and its derivatives are Bcl-2 family proteins containing the anti-apoptosis proteins Bcl-2 and Bcl-XL. The molecular mechanism of gossypol analogs not only involves cell apoptosis but also autophagy, cell cycle arrest, and other abnormal cellular phenomena. Gossypol and its derivatives exert antitumor effects on different cancer types in vitro and in vivo, and demonstrate synergistic effects with other chemo- and radio- therapeutic treatments. In addition, several nanocarriers have been designed to load gossypol or its derivatives in order to expand the range of their applications and evaluate their combination effects with other anti-tumor agents. This review may serve as a reference for the rational application of gossypol analogs as anti-tumor agents.

Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

“…A natural phenol extracted from cottonseed ((-)-gossypol) was shown to reduce MSI1 to bind RNA 45 but this interaction was not validated by structure-activity relationships. Of note, (-)-gossypol has been considered to be a pan-active compound that has hit in multiple HTS screens 48–50 and assigned to have activity against Bcl-2 51 . MSI1 activity was also inhibited by γ-9 monounsaturated fatty acids (e.g.…”

Lytic and sublytic effects of gossypol on red blood cells and thymocytes

“…Gossypol exhibits a range of biological activities including antifertile action, antiviral, antiparasitic, antioxidant and antiproliferative activities 1‐4 . A recent surge of interest to this polyphenol is related to its strong anticancer action as a BH3 mimetic drug 5,6 . Naturally occurring racemic gossypol was able to displace the synthetic BH3 peptide bound to Bcl‐x L antiapoptotic protein with a half‐maximal effect at 0.5 μmol/L 7 .…”

Prenatal Exposure to Gossypol Impairs Corticogenesis of Mouse

“…Previous studies have focused on the toxic effects of gossypol on the reproductive system, and immune function, while reducing resistance to infections, and impairing the efficiency of vaccines (Gadelha et al, 2014b). Cumulative evidence suggests that gossypol exhibits various pharmacological properties such as anti-inflammatory, anti-fungal, anti-fertility, and anti-cancer properties (Moon et al, 2011;Keshmiri-Neghab and Goliaei, 2014;Zeng et al, 2019). Molecular research shows that gossypol causes mitochondrial dysfunction by inhibiting cell respiration.…”