Semaphorin 4D (
Sema4D) has been involved in
cancer progression, the expression of which is associated with the poor clinical outcomes of some
cancer patients.
Dihydromyricetin (DMY) has antitumor potentials for different types of human
cancer cells. However, the pharmacological effects of DMY on
colon cancer (CC) or the regulatory effects of
Sema4D on this process remain largely unknown. In the present study, we aimed to evaluate the effects of DMY on CC, and to elucidate the role of
Sema4D in DMY-induced antitumor effects. DMY inhibited the proliferation and growth of Colo-205
colon cancer cells significantly in vivo and in vitro. DMY inhibited
reactive oxygen species (ROS) and
malondialdehyde (MDA) levels, but increased
glutathione (GSH) level. Moreover, the activities of
antioxidant enzymes catalase (CAT),
superoxide dismutase (SOD),
glutathione peroxidase (GPx),
glutathione reductase (GR) and
heme oxygenase 1 (HO-1) were enhanced by DMY treatment in vitro, showing strong anti-oxidative stress effect. In addition, DMY inhibited the secretion of
interleukin 1β (IL-1β),
interleukin-6 (IL-6),
interleukin-8 (IL-8) and
tumor necrosis factor (TNF-α) in the supernatant of Colo-205 culture medium. Besides, the expressions of
cyclooxygenase (COX-2) and
inducible nitric oxide synthase (iNOS) were suppressed by DMY in dose-dependent manners in vivo, showing potent anti-inflammatory effect. Further investigations showed that DMY suppressed the expression and secretion of
Sema4D in Colo-205 cells and tissues. Interestingly, overexpression of
Sema4D significantly weakened the regulatory effects of DMY on oxidative stress. Furthermore, overexpression of
Sema4D significantly attenuated the anti-inflammatory effects of DMY. Collectively, we drew a conclusion that the anti-
colon cancer effect of DMY was attributed to its negative modulation on oxidative stress and
inflammation via suppression of
Sema4D. The findings broaden the width and depth of molecular mechanisms involved in the DMY action, facilitating the development of DMY in anti-
colon cancer therapies.