Linderalactone Suppresses Pancreatic Cancer Development In Vitro and In Vivo via Negatively Regulating PI3K/AKT
Dongchao Xu1,2,3, Mengyao Tian1, Wangyang Chen1
1Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
Abstract:
Linderalactone is one of the main extracts of Linderae Radix, which is widely used in traditional Chinese medicine. There have been few studies on the antitumor effect of linderalactone in the past. In this study, we explored the anti-pancreatic cancer activity of linderalactone in vitro and in vivo. The results showed that linderalactone inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Cell migration and invasion were significantly inhibited by linderalactone. The cell cycle was arrested in the G2/M phase, and the expression levels of cell cycle-associated proteins changed significantly with linderalactone treatment. In addition, linderalactone induced cell apoptosis and altered the expression of apoptotic markers, such as caspase 3 and PARP1. Mechanistically, linderalactone suppressed the PI3K/AKT signaling pathway by downregulating the phosphorylation of PI3K and AKT. The xenograft study results were consistent with the in vitro results, and there was no obvious chemical toxicity. Thus, our research demonstrated that linderalactone exhibits antitumor activity against pancreatic cancer and may be developed as a potential anti-pancreatic cancer agent in the future.
Insights
Linderalactone, a traditional Chinese medicine extract, effectively inhibits pancreatic cancer cell growth, migration, and invasion. This compound shows potential as a novel anti-pancreatic cancer agent with no observed toxicity in preclinical studies.
Area of Science:
- Pharmacology
- Oncology
- Traditional Chinese Medicine
Background:
- Linderae Radix is utilized in traditional Chinese medicine.
- Linderalactone is a key extract from Linderae Radix.
- Limited research exists on linderalactone's antitumor properties.
Purpose of the Study:
- To investigate the anti-pancreatic cancer effects of linderalactone.
- To evaluate linderalactone's efficacy both in vitro and in vivo.
- To elucidate the underlying mechanisms of linderalactone's action against pancreatic cancer.
Main Methods:
- Cell proliferation, migration, and invasion assays were performed.
- Cell cycle analysis and apoptosis assays were conducted.
- Western blotting was used to assess protein expression and signaling pathways (PI3K/AKT).
- In vivo xenograft studies were performed to evaluate efficacy and toxicity.
Main Results:
- Linderalactone significantly inhibited pancreatic cancer cell proliferation, migration, and invasion in a dose- and time-dependent manner.
- Linderalactone induced G2/M cell cycle arrest and promoted apoptosis by altering caspase 3 and PARP1 expression.
- Linderalactone suppressed the PI3K/AKT signaling pathway.
- In vivo studies confirmed antitumor activity with no significant chemical toxicity.
Conclusions:
- Linderalactone demonstrates significant antitumor activity against pancreatic cancer.
- Linderalactone acts by inhibiting cell proliferation, inducing apoptosis, and suppressing the PI3K/AKT pathway.
- Linderalactone holds promise as a potential therapeutic agent for pancreatic cancer.
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