In this paper, we will outline the current understanding of cell cycle modulation and induction of apoptosis in
cancer cells by natural and synthetic
bile acid.
Bile acid homeostasis is tightly regulated in health, and their cellular and tissue concentrations are restricted. However, when pathophysiological processes impair their biliary secretion, hepatocytes are exposed to elevated concentrations of
bile acids which trigger cell death. In this context, we developed several newly synthesized
bile acid derivatives. These synthetic
bile acids modulated the cell cycle and induced apoptosis in several human
cancer cells similar to natural
bile acids. In human breast and
prostate cancer cells with different
tumor suppressor p53 status, synthetic
bile acid-induced growth inhibition and apoptosis were associated with up-regulation of Bax and p21(WAF1/CIP1) via a p53-independent pathway. In Jurkat human
T cell leukemia cells, the synthetic
bile acids induced apoptosis through
caspase activation. In addition to this, the synthetic
bile acids induced apoptosis in a JNK dependent manner in SiHa human
cervical cancer cells, via induction of Bax and activation of
caspases in PC3
prostate cancer cells and induction of G1 phase arrest in the cell cycle in HT29
colon cancer cells. Moreover, they induced apoptosis in four human
glioblastoma multiform cell lines (i.e., U-118MG, U-87MG, T98G, and U-373MG) and one human TE671
medulloblastoma cells. In addition to this, a
chenodeoxycholic acid derivative, called
HS-1200, significantly decreased the growth of TE671
medulloblastoma tumor size and increased life span in non-obese diabetic and severe combined immunodeficient (NOD/SCID) mice. Therefore, these new synthetic
bile acids, which are novel apoptosis mediators, might be applicable to the treatment of various human
cancer cells.