The heterogeneity and complexity of <i>Cannabis</i> extracts as antitumor agents

Abstract

// Liran Baram 1 , Ella Peled 1 , Paula Berman 1 , Ben Yellin 1 , Elazar Besser 1 , Maya Benami 1 , Igal Louria-Hayon 1 , Gil M. Lewitus 1 and David Meiri 1 1 The Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion - Israel Institute of Technology, Haifa, Israel Correspondence to: David Meiri, email: dmeiri@technion.ac.il Keywords: cancer; Cannabis ; cannabinoids; (-)-&#x0394; 9 - trans -tetrahydrocannabinol (&#x0394; 9 -THC); antitumor Received: March 23, 2019&emsp;&emsp;&emsp;&emsp; Accepted: May 02, 2019&emsp;&emsp;&emsp;&emsp; Published: June 25, 2019 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&#x2019;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 (-)-&#x0394; 9 - trans -tetrahydrocannabinol (&#x0394; 9 -THC) did not produce the same effects on these cell lines as the whole Cannabis extracts. Furthermore, Cannabis extracts with similar amounts of &#x0394; 9 -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&#x2019;s composition as well as on certain characteristics of the targeted cells.