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Orbitides isolated from flaxseed induce apoptosis against SGC-7901 adenocarcinoma cells
Xian-Guo Zou1,2, Jing Li2, Pei-Long Sun1
1College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
Abstract:
Unique plant-derived cyclic peptides family exhibiting various key biological activities has great possibility for anticancer therapy. In this study, we investigated the effects of orbitides isolated from flax (Linum usitatissimum L.) on the growth of SGC-7901 cancer cells and the potential mechanism. Results showed that flaxseed orbitides killed off cancer cells by inducing apoptosis in a dose-dependent manner, which was confirmed by the appearance of nuclear shrinkage and DNA fragmentation, and the inhibitory effect was stronger than that of pure orbitide [1-9-NαC]-linusorb B2 or [1-9-NαC]-linusorb B3. Besides, the mitochondrial apoptosis pathway-related protein cytochrome C (Cyt C) was released from mitochondria to cytosol, associated with the activation of caspases 9 and 3, and the cleavage of PARP. Taken together, these results indicated that flaxseed orbitides induced apoptosis via the mitochondrial pathway, releasing Cyt C, increasing Bax/Bcl-2 ratio and elevating the expression of cleaved caspase 9 and 3 in SGC-7901 cells.
Insights
Flaxseed orbitides effectively kill SGC-7901 cancer cells by inducing apoptosis. These plant-derived compounds activate the mitochondrial pathway, leading to programmed cell death.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Plant-derived cyclic peptides, particularly orbitides, show promise for anticancer therapies.
- Flax (Linum usitatissimum L.) is a source of unique bioactive compounds.
- Understanding the mechanisms of these compounds against cancer cells is crucial.
Purpose of the Study:
- To investigate the anticancer effects of flaxseed orbitides on SGC-7901 cancer cells.
- To elucidate the underlying molecular mechanism of cell death induced by these orbitides.
- To compare the efficacy of flaxseed orbitides with specific pure orbitides.
Main Methods:
- Treatment of SGC-7901 cancer cells with flaxseed orbitides.
- Assessment of apoptosis through nuclear morphology and DNA fragmentation.
- Analysis of mitochondrial apoptosis pathway proteins, including cytochrome C, caspases, and PARP.
- Evaluation of the Bax/Bcl-2 ratio.
Main Results:
- Flaxseed orbitides induced apoptosis in SGC-7901 cells in a dose-dependent manner.
- Apoptosis was characterized by nuclear shrinkage and DNA fragmentation.
- Flaxseed orbitides demonstrated stronger inhibition compared to pure orbitides [1-9-NαC]-linusorb B2 and [1-9-NαC]-linusorb B3.
- The mitochondrial apoptosis pathway was activated, evidenced by cytochrome C release, caspase 9 and 3 activation, and PARP cleavage.
- The Bax/Bcl-2 ratio increased, and cleaved caspase 9 and 3 expression was elevated.
Conclusions:
- Flaxseed orbitides induce apoptosis in SGC-7901 cancer cells via the mitochondrial pathway.
- The mechanism involves cytochrome C release, caspase activation, and modulation of the Bax/Bcl-2 ratio.
- These findings highlight the potential of flaxseed orbitides as a therapeutic strategy for cancer treatment.
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