STAT3 is regarded as a latent transcription factor, which is activated by
tyrosine phosphorylation at position 705 by non-receptor tyrosine kinase, leading to its
dimerization, nuclear translocation, DNA binding, and activation of gene transcription.
Activation of STAT3 is important for the transcription of genes related to cell cycle,
growth, proliferation, migration, and angiogenesis. Under normal physiological
conditions, its upstream signaling that leads to its activation is tightly regulated, but in
cancer, the activation of STAT3 is dysregulated. Studies on various cancer models
suggest that it is constitutively activated in cancer cells and plays a crucial role in the
growth, progression, and metastasis of cancer. It is involved in the induced expression
of procarcinogenic cytokines, such as interleukin-13, and suppressed expression of
Anti-cancer cytokines, such as interleukin-12, indicating shifting of the balancer of
tumor immunity toward tumor growth and progression. Thus it appears to be a
potential target for cancer therapeutics. Several bioactive compounds from natural
sources have been found to interfere with the signaling leading to deregulated STAT3
activation in cancer cells and subsequent cancer suppression/rejection. This chapter
discusses a wide range of natural bioactive compounds that show antitumor effects by
inhibiting STAT3 activation both in vitro and in vivo, as well as their future
perspectives in anti-cancer therapeutics.
Keywords: Apoptosis, Anticancer therapeutics, Cell cycle, Cell proliferation, Cell migration, Lignans, Flavonoids, Metastasis, Polyphenols, STAT3, Tumor growth, Triterpenes.
