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. 2022 Sep 16;27(18):6057.
doi: 10.3390/molecules27186057.

Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts

Dongping Li  1 , Yaroslav Ilnytskyy  1 , Esmaeel Ghasemi Gojani  1 , Olga Kovalchuk  1 , Igor Kovalchuk  1
Affiliations

Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts

Dongping Li et al. Molecules. .

Abstract

Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect-the synergistic or antagonistic effect of various cannabinoids and terpenes. In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells. Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold. We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation. A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA. Our work, thus, showed that most of high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids.

Keywords: Cannabis sativa; anti-cancer property; anti-inflammatory property; delta-9-tetrahydrocannabinol; flower extracts.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Total THC, CBD and CBG content in the flowers (A) and extracts (B). Concentration is shown in the percentage of total weight of dry flowers or extracts prepared from flowers of 25 varieties.
Figure 2
Figure 2
Inhibition of growth of breast cancer cell line HCC1806 and normal cell line BJ-5ta. (A)—growth curve of HCC1806 cells in response to extract #16; (B)—growth curve of BJ-5ta cells in response to extract #16; (C)—growth curve of HCC1806 cells in response to extract #24; (D)—growth curve of BJ-5ta cells in response to extract #24. Cells were treated with 0, 0.007 and 0.015 μg/μL of the above-mentioned extracts for various periods of time, from 0 to 120 h. MTT assay was performed and data were expressed as an average (from 3 independent replicates) with SD. Asterisks indicate significant (p < 0.05) difference from control (0 μg/μL ).
Figure 3
Figure 3
Inhibition of growth of breast cancer cell line HCC1806 and normal cell line BJ-5ta in response to THC. (A)—growth curve of HCC1806 cells in response to 5, 10 and 15 μM of THC; (B)—growth curve of BJ-5ta cells in response to 5, 10 and 15 μM of THC. Y axis shows arbitrary units of cell growth, while X axis shows the time of treatment. MTT assay was performed and data were expressed as an average (from 3 independent replicates) with SD. Asterisks indicate significant (p < 0.05) difference from control (0 μg/μL ).
Figure 4
Figure 4
The effect of selected extracts on the expression of COX2 and IL6 in WI38 cells treated by 10 ng/mL TNF-α/IFN-γ. (A)—Western blot image of COX2, IL6 and GAPDH in response to DMSO, 10 ng/mL TNF-α/IFN-γ, or TNF/IFN together with one of the extracts, from #1 to #7. (B)—ImageJ calculated the densitometry of COX2 for samples #1–#7. (C)—ImageJ calculated the densitometry of IL-6 for samples #1–#7. (D)—Western blot image of COX2, IL6 and GAPDH in response to DMSO, 10 ng/mL TNF-α/IFN-γ, 10 ng/mL TNF-α/IFN-γ plus 5 µM CBD, or TNF/IFN together with one of the extracts—#2, #7, #17, #19 and #24. (E)—ImageJ calculated densitometry of COX2 for samples #2, #7, #17, #19 and #24. (F)—ImageJ calculated densitometry of IL-6 for samples #2, #7, #17, #19 and #24. Data are shown as average relative to GAPDH, calculated from 3 independent measurements, with SE. Asterisks show significant difference from TNF-α/IFN-γ treatment (p < 0.05). NS—non-specific binding.
Figure 5
Figure 5
The effect of various concentrations of THC on the expression of COX2 and IL6 in WI38 cells treated with 10 ng/mL TNF-α/IFN-γ. (A)—Western blot image of COX2, IL6 and GAPDH in response to DMSO, 10 ng/mL TNF-α/IFN-γ, or TNF-α/IFN-γ together with different concentrations of THC. ImageJ calculated the densitometry of COX2 (B) and IL6 (C) relative to GAPDH, calculated from 3 independent measurements, shown as averages with SE. Asterisks show significant difference from TNF-α/IFN-γ treatment (p < 0.05).
Figure 6
Figure 6
Clustering and correlation analysis. (A)—clustering of cultivars according to their terpene concentrations. (B)—PCA analysis according to the terpene concentration. Correlation analysis indicating correlation between the concentration of gamma-terpinene and anti-cancer activity (C), between CBD and alpha-pinene levels (D), CBGA and terpinolene (E), CBGA and p-cymene (F) and CBGA and isopulegol (G). Open circles indicate individual extracts.
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