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In-vitro Evaluation Of Cannabinoids In Combination with Terpenes In Overcoming Cancer Resistance

Mounika Aare
Florida A&M University

Co-Authors: Sukhmandeep Kaur1, Breana Boire1, Mandip Singh Sachdeva1
1Florida A&M University

To study the effect of combinations of various cannabinoids and terpenes against cancer resistance.

Several cannabinoids such as cannabidiol (CBD), cannabichromene (CBC), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabinol (CBN), cannabigerol (CBG) were screened for their anticancer activity against MDA MB 231 DOX RT, H1975 OSM RT, PDX Lung cancer cell lines using 2D cytotoxicity and 3D spheroids assay. Terpenes such as β-caryophyllene, bisabolol, myrcene, linalool, limonene, geraniol, neralidol, α-pinene, α-terpineol, γ-terpinene were tested individually against MDA MB 231 DOX RT, H1975 OSM RT, PDX Lung cancer cell lines for their anticancer potential in 2D cytotoxicity and 3D spheroid assay. The potential cannabinoids (all) and terpenes (β-caryophyllene) obtained from the individual screening were tested in combinations against resistance cancer cell lines. The mode of action of combinations either synergistic, additive or antagonistic was determined from combination index (CI) values using compusyn software. Other assays such as colony formation assay and wound healing assay were performed using the potential combinations obtained. The anticancer activity of combination was also confirmed by live/dead staining using Hoechst’s stain. The anticipated mechanism of action by which cannabinoids acts along with terpenes in overcoming resistance are through mitogen-activated protein kinase (MAPK), Phosphatidylinositol 3-Kinase (PI3K) pathway, epigenetics histone modifications.

The IC50 values of cannabinoids were found to be around 10µM against all the three resistant cancer cell lines in a 2D cytotoxicity assay. The IC50 values of β-caryophyllene and bisabolol were found to be 35µM and 90µM respectively in 2D cytotoxicity assay. Other terpenes screened had IC50 values more than 150µM and hence were not studied further. The IC50 values of combinations of cannabinoids and β-caryophyllene decreased by 10 folds and was 1µM for all the combinations. Same pattern was replicated in 3D spheroid assay i.e., the IC50 values dropped from 50µM to 6µM. The colony formation ability of cells post treatment with combinations reduced significantly(p<0.001).

The results obtained emphasizes that combinations of cannabinoids and terpenes plays a magical role in overcoming cancer resistance.

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