Oleanolic acid inhibits proliferation and invasiveness of Kras-transformed cells via autophagy
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Updated: Apr 25, 2026

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Published on: January 31, 2025
Jia Liu1, Lanhong Zheng2, Leina Ma3
1College of Medicine, Qingdao University, Qingdao 266021, China; Institutes of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
Abstract:
Oleanolic acid (OA) has been widely studied because of its pleiotropic therapeutic and preventive effect on various diseases. However, the mechanisms of OA's action are still not clear yet, especially its suppressing effect on transformed cells. In this work, we found that OA induced autophagy in normal tissue-derived cells without cytotoxicity. OA-induced autophagy was shown to decrease the proliferation of KRAS-transformed normal cells and to impair their invasion and anchorage-independent growth. Interrupting autophagy rescued OA's effect on the transformed cells. Mouse model experiments also demonstrated that OA suppressed the growth of KRAS-transformed breast epithelial cell MCF10A-derived tumor xenograft by inducing autophagy. Finally, we identified that OA induced autophagy in normal cells by inhibiting the activation of Akt/mTOR/S6K signaling. In conclusions, we found that OA treatment permitted normal cells to undergo autophagy. The induced autophagy was required for OA to prevent or delay the growth of transformed normal cells.
Insights
Oleanolic acid (OA) triggers autophagy in normal cells, which then suppresses the growth of KRAS-transformed cells. This autophagy induction is key to OA's preventive effects on cancer development.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Oleanolic acid (OA) exhibits diverse therapeutic effects, but its mechanism against transformed cells remains unclear.
- Understanding OA's action is crucial for developing novel cancer prevention strategies.
Purpose of the Study:
- To elucidate the mechanism by which Oleanolic acid (OA) suppresses transformed cells.
- To investigate the role of autophagy in OA's anti-cancer effects.
Main Methods:
- Induction of autophagy in normal and KRAS-transformed cells using OA.
- Assessment of cell proliferation, invasion, and anchorage-independent growth.
- In vivo tumor xenograft studies in a mouse model.
- Analysis of the Akt/mTOR/S6K signaling pathway.
Main Results:
- OA induced autophagy in normal cells without cytotoxicity.
- OA-induced autophagy inhibited proliferation and invasion of KRAS-transformed cells.
- Blocking autophagy abolished OA's suppressive effects on transformed cells.
- OA suppressed tumor growth in a xenograft model by inducing autophagy.
- OA inhibited Akt/mTOR/S6K signaling to induce autophagy.
Conclusions:
- Oleanolic acid (OA) treatment induces autophagy in normal cells.
- This OA-induced autophagy is essential for preventing or delaying the growth of transformed normal cells.
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