Total flavonoids of Oldenlandia diffusa (Willd.) Roxb. suppresses the growth of hepatocellular carcinoma through endoplasmic reticulum stress-mediated autophagy and apoptosis

Abstract

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world. Although the current treatment methods for HCC are gradually increasing, its efficacy still cannot meet the medical needs of patients with liver cancer, and new and effective treatment strategies are urgently needed. The total flavonoids of Oldenlandia diffusa (FOD) are the main active components in Oldenlandia diffusa, which have anti-inflammatory, antioxidant and anti-tumor effects, but their mechanism of action in liver cancer is unclear. In this study, we examined the effect of FOD on HCC. Using both in vitro and in vivo models, we confirmed that FOD inhibited HCC proliferation and induced apoptosis and autophagy. Mechanistic studies have shown that FOD induces apoptosis and activates autophagy in HCC cells by inducing endoplasmic reticulum stress (ER stress) and activating the PERK-eIF2α-ATF4 signaling pathway. Taken together, our results suggest that FOD is a potential anticancer drug targeting ER stress for the treatment of HCC.

Upregulation of FAM134B inhibits endoplasmic reticulum stress‐related degradation protein expression and promotes hepatocellular carcinogenesis

“…Studies have revealed that endoplasmic reticulum stress can inhibit the expression of autophagy‐related genes, including ATG12 and ATG5, allowing liver cancer cells to evade autophagic degradation and enhance their capacity for growth and proliferation. Consequently, the role of autophagy in liver cancer cells is counteracted by endoplasmic reticulum stress 30 . In conclusion, the interplay between ER stress and cell autophagy plays a crucial role in the progression of liver cancer.…”

“…Consequently, the role of autophagy in liver cancer cells is counteracted by endoplasmic reticulum stress. 30 In conclusion, the interplay between ER stress and cell autophagy plays a crucial role in the progression of liver cancer. Hence, future investigation should focus on elucidating the underlying mechanisms of this interaction to pave the way for novel therapeutic strategies in liver cancer.…”

Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms

“…Studies have shown that the alkaloid veratramine significantly inhibits the proliferation, migration, and invasion of HepG2 cells and induces autophagy-mediated cell death by inhibiting the PI3K/Akt/mTOR signaling pathway [ 96 ]. Both in vitro and in vivo studies have demonstrated that the main active component, total flavonoids of Hedyotis diffusa Willd, induces endoplasmic reticulum stress (ER stress) and activates the PERK/EIF2α/ATF4 signaling pathway, inducing apoptosis and activating autophagy in HCC cells [ 60 ].…”