Parthenolide suppresses pancreatic cell growth by autophagy-mediated apoptosis
Weifeng Liu1, Xinshuai Wang2, Junjun Sun1
1Department of Hepatobiliary Surgery.
Abstract:
Pancreatic cancer is an aggressive malignancy and is unresponsive to conventional chemotherapies. Parthenolide, a sesquiterpene lactone isolated from feverfew, has exhibited potent anticancer effects against various cancers. The purpose of this report was to investigate the effect and underlying mechanism of parthenolide in human pancreatic cancer Panc-1 and BxPC3 cells. The results demonstrated that parthenolide suppressed the growth and induced apoptosis of Panc-1 and BxPC3 pancreatic cancer cells with the half maximal inhibitory concentration (IC50) ranging between 7 and 9 μM after 24 h of treatment. Significant autophagy was induced by parthenolide treatment in pancreatic cancer cells. Parthenolide treatment concentration-dependently increased the percentage of autophagic cells and significantly increased the expression levels of p62/SQSTM1, Beclin 1, and LC3II in Panc-1 cells. Punctate LC3II staining confirmed autophagy. Furthermore, inhibiting autophagy by chloroquine, 3-methyladenine, or LC3II siRNA significantly blocked parthenolide-induced apoptosis, suggesting that parthenolide induced apoptosis through autophagy in this study. In conclusion, these studies established that parthenolide inhibits pancreatic cell growth by autophagy-mediated apoptosis. Data of the present study suggest that parthenolide can serve as a potential chemotherapeutic agent for pancreatic cancer.
Insights
Parthenolide, derived from feverfew, effectively inhibits pancreatic cancer cell growth and induces apoptosis. This anticancer effect is mediated through autophagy, suggesting its potential as a novel chemotherapy agent.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Pancreatic cancer is a highly aggressive malignancy with limited treatment options.
- Parthenolide, a natural compound, shows promise as an anticancer agent.
- Understanding its mechanism in pancreatic cancer is crucial for therapeutic development.
Purpose of the Study:
- To investigate the effects of parthenolide on human pancreatic cancer cell lines (Panc-1 and BxPC3).
- To elucidate the underlying mechanism of parthenolide-induced cell death, focusing on autophagy.
Main Methods:
- Cell viability assays to determine IC50 values.
- Analysis of autophagy markers (p62/SQSTM1, Beclin 1, LC3II) and autophagic cell percentage.
- Inhibition of autophagy using chloroquine, 3-methyladenine, or LC3II siRNA to assess its role in apoptosis.
Main Results:
- Parthenolide suppressed pancreatic cancer cell growth and induced apoptosis with IC50 values between 7-9 μM.
- Parthenolide significantly increased autophagy in a concentration-dependent manner.
- Inhibition of autophagy blocked parthenolide-induced apoptosis, confirming autophagy's role.
Conclusions:
- Parthenolide inhibits pancreatic cancer cell growth via autophagy-mediated apoptosis.
- Parthenolide demonstrates potential as a chemotherapeutic agent for pancreatic cancer.
