Cancer Initiation, Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds?

Abstract

Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.

The Origin and Biomedical Relevance of Cannabigerol

“…The oil is a valued source of linoleic (LA), α-linolenic (ALA), oleic (OA), γ-linolenic (GLA), stearidonic (SDA), and cis-vaccenic acids [16]. Phytocannabinoids are a group of 21-carbon terpenophenolic compounds [19]. To date, more than 120 phytocannabinoids have been isolated from cannabis, including two compounds, (−)-trans-Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and (−)-trans-Δ 8 -tetrahydrocannabinol (Δ 8 -THC), which produce the characteristic psychotropic effect by binding to cannabinoid receptors [20].…”

Phytocannabinoids in the Pharmacotherapy of Psoriasis

“…However, phytocannabinoids are a group of compounds naturally present in plants, mainly in true hemp ( Cannabis sativa L., cannabis) [ 4 ]. The group primarily includes 21-carbon (22-carbon if present in the form of acid) terpenophenolics [ 4 , 5 ]. Many of these compounds are biosynthesized from olivetolic acid (OLA) and geranyl diphosphate (GPP) in trichomes, i.e., outgrowths located on almost the whole surface of the plant [ 6 ].…”

Repositioning Cannabinoids and Terpenes as Novel EGFR-TKIs Candidates for Targeted Therapy Against Cancer: A virtual screening model using CADD and biophysical simulations

“…Due to the lack of efficient treatments accessible to all populations at the lowest cost and with less toxicity, efforts of researchers have turned towards medicinal plants such as Cannabis sativa L. and their therapeutic benefits against breast and lung cancer [ [26] , [27] , [28] ]. The World Health Organization (WHO) reported 10.44 million cancer deaths in 2020, including 2.26 million cases of breast cancer, 2.21 million cases of lung cancer, 1.93 million cases of colon and rectal cancer, 1.41 million cases of prostate cancer, 1.20 million cases of non-melanoma skin cancer, and 1.09 million cases of stomach cancer [ [29] , [30] , [31] ].…”