Ingenane-type diterpenoids inhibit non-small cell lung cancer cells by regulating SRC/PI3K/Akt pathway

Abstract

Ingenane-type diterpenoids (ITDs) are distinct components of plants belonging to the genus Euphorbia. These compounds have significant cytotoxic effects on non-small cell lung cancer (NSCLC) cells. However, the underlying molecular mechanism has yet to be reported. To explore the mechanism of the anticancer effect of ITDs, we carried out a network pharmacology prediction study. PPI network suggested that SRC and PI3K had high levels of interaction. In addition, KEGG analysis revealed that these common targets were significantly enriched in the PI3K/Akt signalling pathway. 13-oxyingenol-dodecanoate (13OD) was used for validation after the biological evaluation of some ITDs against NSCLC cells. It demonstrated that 13OD could significantly inhibit the growth of NSCLC cells by inducing apoptosis. The results from molecular docking and Western blotting showed that 13OD interacted with SRC and PI3K and down-regulated the SRC/PI3K/Akt signalling pathway in NSCLC cells. This study provided the underlying mechanism of ITDs against NSCLC.

Graphic Abstract

Keywords:

• Non-small cell lung cancer
• ingenane-type diterpenoids
• 13-oxyingenol-dodecanoate
• SRC/PI3K/akt pathway

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Plan of Shenyang Young and Middle-aged Science and Technology Innovation Talents Support (RC210451); the Scientific Research Fund Project of Liaoning Provincial Department of Education (LJKZ0907); Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD-D-202208); the Outstanding and Excellent Youth Talent Support Program of Shenyang Pharmaceutical University (ZQ202201, YQ202104).