hispidulin and Lung-Neoplasms

Hispidulin is a medicinal natural compound isolated from S. involucrata, which exhibits potent anticancer properties. However, there are few reports on its effects on lung cancer cells. Therefore, the current study investigated the effects of hispidulin on cell viability and apoptosis in human non‑small‑cell lung cancer (NSCLC) cell lines NCI‑H460 and A549 in vitro and in vivo. Methyl thiazolyl tetrazolium, colony formation assay, Hoechst 33342 staining, flow cytometry and western blotting were performed on Human NCI‑H460 and A549 cells. A mouse xenograft model was also established using NCI‑H460 cells. The results showed that the growth of NCI‑H460 and A549 cells was inhibited, while apoptosis was promoted by hispidulin via increased generation of reactive oxygen species (ROS) in a dose‑dependent manner. Furthermore, hispidulin triggered apoptosis in NSCLC cells through upregulating the expression of cleaved caspase‑3 and cleaved poly [ADP‑ribose] polymerase. All these effects were reversed upon pretreatment with glutathione, a selective ROS inhibitor. In addition, endoplasmic reticulum stress (ER stress) in NCI‑H460 cells was activated by hispidulin. Pretreatment with tauroursodeoxycholic acid, a specific ER stress inhibitor, effectively reduced the cell apoptosis induced by hispidulin. In conclusion, hispidulin induces ROS‑mediated apoptosis via activating the ER stress pathway. The current study provides theoretical basis for the antitumor effect of hispidulin in NSCLC.

Topics: A549 Cells; Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Endoplasmic Reticulum Stress; Flavones; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Mice; Reactive Oxygen Species; Xenograft Model Antitumor Assays

Colorectal cancer (CRC) accounts for over 600 000 deaths annually worldwide. The current study aims to evaluate the value of proto-oncogene PIM1 as a therapeutic target in CRC and investigate the anticancer activity of hispidulin, a naturally occurring phenolic flavonoid compound, against CRC. Immunohistochemistry analysis showed that PIM1 was upregulated in CRC tissue. The role of PIM1 as an oncogene was evidenced by the fact that PIM1 knockdown inhibits cell growth, induces apoptosis, and suppresses invasion. Our results showed that hispidulin exerts antitumor activity in CRC through inhibiting the expression of PIM1. Moreover, our findings revealed that hispidulin downregulated the expression of PIM1 by inhibiting JAK2/STAT3 signaling by generating reactive oxygen species. Furthermore, our in vivo studies showed that hispidulin can significantly inhibit tumor growth and metastasis in CRC. Collectively, our results provide an experimental basis for trialing hispidulin in CRC treatment. PIM1 can be considered a potential therapeutic target in CRC.

Topics: Animals; Cell Line, Tumor; Colorectal Neoplasms; Female; Flavones; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Janus Kinase 2; Lung Neoplasms; Male; Mice; Proto-Oncogene Mas; Proto-Oncogene Proteins c-pim-1; Reactive Oxygen Species; Signal Transduction; STAT3 Transcription Factor; Up-Regulation; Xenograft Model Antitumor Assays