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Published on: March 30, 2019
14-Deoxycoleon U-induced endoplasmic reticulum stress-mediated apoptosis, autophagy, and cell cycle arrest in lung
Xiaozhi Peng1, Yijun Tu1, San Fu2
1Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Department of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, 430065, People's Republic of China.
Objective:
14-Deoxycoleon U is a natural abietane-type diterpene and exerts an inhibitory effect on tumor cells proliferation, which suggests that 14-Deoxycoleon U may be a potent anti-cancerous lead compound for lung cancer treatment. This study was to evaluate potential of 14-Deoxycoleon U to treat lung adenocarcinoma in vitro and in vivo.
Methods:
In the present study, the cell viability and apoptosis morphology of 14-Deoxycoleon U-treated A549 and LLC cells were explored using cell counting kit-8 assay and Hoechst 33258 staining. Then, the protein expressions about apoptosis, endoplasmic reticulum (ER) stress, autophagy and cell cycle were measured using Western blot. The autophagosome formation of 14-Deoxycoleon U-treated A549 cells was visualized using a confocal microscopy. LLC lung adenocarcinoma model was established.
Results:
The results indicated that 14-Deoxycoleon U significantly inhibited A549 and LLC cell proliferation in a dose-dependent manner via caspase-dependent apoptosis. Furthermore, apoptosis of both cells was mediated by 14-Deoxycoleon U-induced ER stress. In addition, 14-Deoxycoleon U-induced A549 and LLC cell autophagy, thus promoting their death. Moreover, 14-Deoxycoleon U-induced cell cycle arrest in both cells via inhibition of cyclin D3, cyclin-dependent kinase 6, CDC2 and up-regulation of p21. In vivo results showed that administration of 14-Deoxycoleon U significantly suppressed LLC growth and adverse effects of 14-Deoxycoleon U on organs might be lower than of adriamycin.
Conclusion:
Overall, our results demonstrated that 14-Deoxycoleon U represses in vitro and in vivo growth of lung adenocarcinoma through ER stress-mediated apoptosis accompanied by autophagy and cell cycle arrest.
Insights
14-Deoxycoleon U effectively inhibits lung adenocarcinoma cell proliferation by inducing apoptosis, endoplasmic reticulum stress, and autophagy. This natural compound shows promise for treating lung cancer in vitro and in vivo.
Area of Science:
- Pharmacology
- Cancer Biology
- Molecular Biology
Background:
- 14-Deoxycoleon U is a natural abietane-type diterpene with demonstrated inhibitory effects on tumor cell proliferation.
- Lung adenocarcinoma is a significant global health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the potential of 14-Deoxycoleon U as a therapeutic agent for lung adenocarcinoma.
- To investigate the in vitro and in vivo efficacy of 14-Deoxycoleon U against lung adenocarcinoma.
Main Methods:
- Cell viability and apoptosis were assessed using cell counting kit-8 assay and Hoechst 33258 staining.
- Western blot analysis was employed to measure protein expression related to apoptosis, ER stress, autophagy, and cell cycle.
- Autophagosome formation was visualized via confocal microscopy, and an in vivo LLC lung adenocarcinoma model was established.
Main Results:
- 14-Deoxycoleon U significantly inhibited A549 and LLC cell proliferation in a dose-dependent manner, inducing caspase-dependent apoptosis.
- Apoptosis was mediated by 14-Deoxycoleon U-induced endoplasmic reticulum stress and promoted by autophagy.
- Cell cycle arrest was observed, linked to modulation of key cell cycle regulatory proteins.
Conclusions:
- 14-Deoxycoleon U demonstrates significant anti-cancer activity against lung adenocarcinoma both in vitro and in vivo.
- The compound's efficacy is attributed to ER stress-mediated apoptosis, autophagy, and cell cycle arrest.
- 14-Deoxycoleon U presents a promising lead compound for lung cancer treatment with potentially lower adverse effects than adriamycin.
