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Pro-Apoptotic Activity and Cell Cycle Arrest of Caulerpa sertularioides against SKLU-1 Cancer Cell in 2D and 3D
Rosette Agena1, Alejandro De Jesús Cortés-Sánchez2, Humberto Hernández-Sánchez1
1Ingeniería Bioquímica-Escuela Nacional de Ciencias Biológicas (ENCB)-Instituto Politécnico Nacional, Ciudad de México 07738, Mexico.
Abstract:
Cancer is a disease with the highest mortality and morbidity rate worldwide. First-line drugs induce several side effects that drastically reduce the quality of life of people with this disease. Finding molecules to prevent it or generate less aggressiveness or no side effects is significant to counteract this problem. Therefore, this work searched for bioactive compounds of marine macroalgae as an alternative treatment. An 80% ethanol extract of dried Caulerpa sertularioides (CSE) was analyzed by HPLS-MS to identify the chemical components. CSE was utilized through a comparative 2D versus 3D culture model. Cisplatin (Cis) was used as a standard drug. The effects on cell viability, apoptosis, cell cycle, and tumor invasion were evaluated. The IC50 of CSE for the 2D model was 80.28 μg/mL versus 530 μg/mL for the 3D model after 24 h of treatment exposure. These results confirmed that the 3D model is more resistant to treatments and complex than the 2D model. CSE generated a loss of mitochondrial membrane potential, induced apoptosis by extrinsic and intrinsic pathways, upregulated caspases-3 and -7, and significantly decreased tumor invasion of a 3D SKLU-1 lung adenocarcinoma cell line. CSE generates biochemical and morphological changes in the plasma membrane and causes cell cycle arrest at the S and G2/M phases. These findings conclude that C. sertularioides is a potential candidate for alternative treatment against lung cancer. This work reinforced the use of complex models for drug screening and suggested using CSE's primary component, caulerpin, to determine its effect and mechanism of action on SKLU-1 in the future. A multi-approach with molecular and histological analysis and combination with first-line drugs must be included.
Insights
Marine algae extract from Caulerpa sertularioides (CSE) shows potential as an alternative lung cancer treatment. CSE effectively reduced tumor invasion and induced cancer cell death, offering a promising avenue for novel therapies.
Area of Science:
- Marine Biotechnology
- Cancer Research
- Pharmacology
Background:
- Cancer poses a significant global health burden with limited treatment options.
- Conventional cancer drugs often cause severe side effects, impacting patient quality of life.
- Marine macroalgae represent a rich source of novel bioactive compounds for therapeutic development.
Purpose of the Study:
- To investigate the anti-cancer potential of Caulerpa sertularioides extract (CSE) against lung adenocarcinoma.
- To compare the efficacy of CSE in 2D versus 3D cell culture models.
- To elucidate the mechanisms of action of CSE in cancer cells.
Main Methods:
- An 80% ethanol extract of Caulerpa sertularioides (CSE) was prepared and analyzed using High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS).
- Comparative efficacy studies were conducted using 2D and 3D cell culture models of SKLU-1 lung adenocarcinoma.
- Assays included cell viability, apoptosis induction, cell cycle analysis, and tumor invasion assays, with Cisplatin (Cis) as a control.
Main Results:
- CSE demonstrated significant anti-cancer activity, with varying IC50 values between 2D (80.28 μg/mL) and 3D (530 μg/mL) models, highlighting the complexity of 3D models.
- CSE induced apoptosis via both extrinsic and intrinsic pathways, upregulated caspases-3 and -7, and reduced mitochondrial membrane potential.
- CSE significantly inhibited tumor invasion and caused cell cycle arrest at the S and G2/M phases in a 3D lung adenocarcinoma model.
Conclusions:
- Caulerpa sertularioides extract (CSE) exhibits promising anti-cancer properties against lung adenocarcinoma, particularly in complex 3D models.
- CSE's mechanism involves inducing apoptosis, disrupting mitochondrial function, and inhibiting tumor invasion.
- Further research into caulerpin, a primary component of CSE, is warranted for developing novel lung cancer therapeutics.
