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Published on: January 19, 2019
Deoxypodophyllotoxin inhibits lung adenocarcinoma growth through regulation of FOXO1 nuclear translocation
Feng Zhou1, Linxi Lv2, Jiahui Wen3
1First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Abstract:
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer and remains associated with high mortality despite advances in current therapies. Deoxypodophyllotoxin (DPT), a natural lignan derived from Anthriscus sylvestris, has been reported to exhibit antitumor activity in multiple cancer types; however, its molecular mechanism of action in LUAD has not been fully elucidated. In this study, we investigated the antitumor effects of DPT in LUAD and explored the involvement of Forkhead box O1 (FOXO1) signaling. Using LUAD cell lines and a xenograft mouse model, we found that DPT significantly inhibited cell proliferation and migration, induced apoptosis, and suppressed tumor growth in vivo. Mechanistic analyses revealed that FOXO1 was predominantly localized in the cytoplasm of LUAD cells under basal conditions. DPT treatment reduced FOXO1 phosphorylation and promoted its translocation into the nucleus, accompanied by enhanced FOXO1-associated antitumor effects. Functional experiments further supported a contributory role of FOXO1 in mediating the cellular response to DPT. Collectively, these findings demonstrate that DPT suppresses LUAD progression and identify FOXO1 as a mechanistically relevant downstream target of DPT. This study provides new insight into the molecular basis of DPT's anticancer activity and highlights FOXO1 signaling as an important component of its antitumor mechanism in LUAD.
Insights
Deoxypodophyllotoxin (DPT) effectively suppresses lung adenocarcinoma (LUAD) progression by inhibiting cell growth and promoting apoptosis. This natural compound targets Forkhead box O1 (FOXO1) signaling, enhancing its nuclear translocation for antitumor effects.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Lung adenocarcinoma (LUAD) presents a significant global health challenge due to high mortality rates.
- Current therapies for LUAD have limitations, necessitating the exploration of novel therapeutic agents.
- Deoxypodophyllotoxin (DPT), a natural lignan, shows potential antitumor activity, but its mechanism in LUAD requires elucidation.
Purpose of the Study:
- To investigate the antitumor effects of Deoxypodophyllotoxin (DPT) in lung adenocarcinoma (LUAD).
- To explore the role of Forkhead box O1 (FOXO1) signaling in mediating DPT's effects on LUAD.
Main Methods:
- Utilized LUAD cell lines and a xenograft mouse model to assess DPT's efficacy.
- Examined DPT's impact on cell proliferation, migration, apoptosis, and tumor growth.
- Investigated FOXO1 localization and phosphorylation status following DPT treatment.
Main Results:
- DPT significantly inhibited LUAD cell proliferation and migration, and induced apoptosis in vitro.
- DPT suppressed tumor growth in vivo in a xenograft mouse model.
- DPT treatment reduced FOXO1 phosphorylation, promoting its nuclear translocation and enhancing antitumor activity.
Conclusions:
- Deoxypodophyllotoxin (DPT) demonstrates potent antitumor effects against lung adenocarcinoma (LUAD).
- FOXO1 signaling is a key downstream target mediating DPT's anticancer mechanisms in LUAD.
- DPT represents a promising therapeutic candidate for LUAD, with FOXO1 as a critical mediator.
