The Potential Anti-Tumor Extract Of Ocimum Basilicum Lamiaceae Towards Colorectal Cancer Via The Angiogenesis Mechanistic Pathway
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Date
2021-03
Authors
Al Deeb, Ibrahim Deeb Tawfiq
Journal Title
Journal ISSN
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Publisher
Universiti Sains Malaysia
Abstract
Angiogenesis is a process of new blood vessel development which can be triggered by inflammation. Both processes play crucial role in colorectal cancer. Natural products that have high level of antioxidants are known to have anti-inflammatory and anti-angiogenic activity and hence could be useful to treat colon cancer. In this work present here, methanolic extracts of 19 plant species of lamiaceae family found in Saudi Arabia were screened for their anti-angiogenic activity to ascertain their potency towards colon cancer. Only six extracts inhibited neovascularization formation by 50% or more, namely Thymbra capitate (Arial part) (97.93±2.63%), Premna resinosa (Stem) (85.03±16.84%), Phlomis viscosa Poir (Arial part) (81.47±22.95%), Salvia samuelssonii (Arial part) (55.69±12.72%), Ocimum basilicum (Leaves) (54.55 ± 4.27%) and Ocimum basilicum (Arial part) (53.99 ± 8.75%). However, methanolic extract of Ocimum basilicum (OB) leaves shown the highest inhibition towards endothelial cells proliferation and migration among other extracts. (OB) leaves were extracted with 70% ethanol (OBL70) at 55 ⁰C, causing a 43% increase in the anti-angiogenic properties compared to methanolic extract. OBL70 was studied in vitro against endothelial cells proliferation, cytotoxicity, migration, invasion and capillary-like structures using MTT, colony formation, scratch, invasion and tube formation assays, respectively. Its IC50 value after 96 h treatment was 79.78± 2.35 μg/ml. OBL70 at 100 μg/ml was able to inhibit colony formation, migration, invasion and tube formation by 71.6±4.1, 59.1±1.17, 31.51± 2.37 and 100±0.0 % in respect to untreated groups, in a dose-dependent manner, respectively. The anti-tumor properties of OBL70 against in vitro co-cultured 2D spheroids model revealed that 200 μg/ml concentration could inhibit the spheroids growth by 40.15 ± 9.99 % compared to untreated group after 13 days treatment. The GC-MS chemical identification revealed the presence of 77 compounds. Of these, three compounds with highest abundance, namely (+)-Epi-bicyclosesquiphellandrene (7.83%), 2-Methoxy-4-vinylphenol (3.54 %) and Eugenol (3.3 %). The molecular mechanism of OBL70 against endothelial cells revealed significant inhibition for the release of IL-8, Leptin and VEGFR-2 by 82, 65 and 55% compared to untreated group. (+)-Epi-bicyclosesquiphellandrene also showed the highest binding affinities against all targeted proteins with more potent inhibitory effect in molecular docking studies. In conclusion, OBL70 of Ocimum basilicum extract shows potential anti-tumor properties against colorectal cancer via the inhibition of endothelial cells angiogenic factors; IL-8, Leptin and VEGFR-2 by its major compounds (+)-Epi-bicyclosesquiphellandrene (7.83%), 2-Methoxy-4-vinylphenol (3.54 %) and Eugenol (3.3 %) . This highlights its potential application in clinical setting for treating colon cancer.
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Keywords
Cancer