Abstract
The Cannabis plant contains over 100 phytocannabinoids and hundreds of other components. The biological effects and interplay of these Cannabis compounds are not fully understood and yet influence the plant’s therapeutic effects. Here we assessed the antitumor effects of whole Cannabis extracts, which contained significant amounts of differing phytocannabinoids, on different cancer lines from various tumor origins. We first utilized our novel electrospray ionization liquid chromatography mass spectrometry method to analyze the phytocannabinoid contents of 124 Cannabis extracts. We then monitored the effects of 12 chosen different Cannabis extracts on 12 cancer cell lines. Our results show that specific Cannabis extracts impaired the survival and proliferation of cancer cell lines as well as induced apoptosis. Our findings showed that pure (-)-Δ9-trans-tetrahydrocannabinol (Δ9-THC) did not produce the same effects on these cell lines as the whole Cannabis extracts. Furthermore, Cannabis extracts with similar amounts of Δ9-THC produced significantly different effects on the survival of specific cancer cells. In addition, we demonstrated that specific Cannabis extracts may selectively and differentially affect cancer cells and differing cancer cell lines from the same organ origin. We also found that cannabimimetic receptors were differentially expressed among various cancer cell lines and suggest that this receptor diversity may contribute to the heterogeneous effects produced by the differing Cannabis extracts on each cell line. Our overall findings indicate that the effect of a Cannabis extract on a specific cancer cell line relies on the extract’s composition as well as on certain characteristics of the targeted cells.
Highlights
Of the over 500 different compounds present in the Cannabis plant, currently more than 120 have been identified as phytocannabinoids, the unique bioactive compounds of the Cannabis plant [1]
We found that the A549 and NCI-H460 cancer cell lines were statistically more sensitive to specific Cannabis extracts CAN2, CAN5, CAN7, CAN9, and CAN10 compared to normal airway epithelial cells (AECs) (Figure 6A-6B)
This study demonstrates the anti-cancer activity of various whole Cannabis extracts on a set of human cancer cell lines
Summary
Of the over 500 different compounds present in the Cannabis plant, currently more than 120 have been identified as phytocannabinoids, the unique bioactive compounds of the Cannabis plant [1]. Many of the phytocannabinoids found in Cannabis affect the endocannabinoid system (ECS), a principal endogenous signaling system that appeared early in evolution and has important regulatory functions throughout the body [6,7,8]. This system consists of two main cannabinoid receptors (CB1 and CB2). Following the terminology by Leishman et al, 2015 [11], receptors which interact www.oncotarget.com with cannabinoids are referred to as “cannabimimetic receptors” Some of these receptors were found to be upregulated in cancer, conflicting reports exist regarding the role of the ECS in tumor generation and progression [12,13,14,15,16,17]
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