Chemical characterization of non‐psychoactive Cannabis sativa L. extracts, in vitro antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells

Abstract

In this study, extracts from non‐psychoactive Cannabis sativa L. varieties were characterized by means of ultra high‐performance liquid chromatography coupled with high‐resolution mass spectrometry (UHPLC‐HRMS) and their antiproliferative activity was assessed in vitro. The human chronic myelogenous leukaemia cell line K562 was chosen to investigate the mechanism of cell death. The effect on the cell cycle and cell death was analysed by flow cytometry. Proteins related to apoptosis were studied by western blotting. Mechanical properties of cells were assessed using the Micropipette Aspiration Technique (MAT). The results indicated that the cannabidiol (CBD)‐rich extract inhibited cell proliferation of K562 cell line in a dose‐dependent manner and induced apoptosis via caspase 3 and 7 activation. A significant decrease in the mitochondrial membrane potential was detected, together with the release of cytochrome c into the cytosol. The main apoptotic markers were not involved in the mechanism of cell death. The extract was also able to modify the mechanical properties of cells. Thus, this hemp extract and its pure component CBD deserve further investigation for a possible application against myeloproliferative diseases, also in association with other anticancer drugs.

A label free chemoproteomic-based platform to disclose cannabidiol molecular mechanism of action on chronic myelogenous leukemia cancer cells

“…Even though several researches defined the CBD-mediated anti-proliferative activity in cancer cell lines through the action on its putative endogenous receptors CB1 and CB2 and on GPR55 or TRPV1 [ 27 ], the exact molecular mechanism of action of this compound is still unknown. Recent interesting studies have demonstrated that CBD can inhibit the proliferation of human chronic myelogenous leukemia K562 cancer cells by inducing apoptosis, together with a drop of the mitochondrial membrane potential and the stimulation of caspase 3 and 7 [ 14 ]. Remarkably, the protein expression levels of the above-mentioned receptors were low or absent in the K562 cell line as far as regard the CB2 and thus they cannot be accountable of the antiproliferative activity of CBD ( https://www.proteinatlas.org ).…”

“…For the following Western blot experiments performed on protein extracts obtained from K562 cell line, cells were treated for 24 h with CBD 20 μM, corresponding to the IC 25 as optimized by Ref. [ 14 ]. Proteins from both the control and the treated K562 cancer cell line were obtained by lysing and homogenized (in ice) the samples in RIPA buffer with 2 mM phenylmethylsulfonyl fluoride (Merck Life Science S.r.l., Italy).…”

“…Recent studies exposed that CBD decreases the proliferation of human chronic myelogenous leukemia K562 cancer cells by prompting apoptosis, occurring by targeting the cytochrome c in the cytosol together with the reduction of the mitochondrial membrane potential and the activation of caspase 3 and 7 [ 14 ]. To shed light on CBD apoptotic action mechanism, this study is focalized on the identification of its interactome in K562 cancer cells by using a functional proteomic platform initially based on the DARTS.…”

Exploring the Therapeutic Potential of Cannabis Constituents in Parkinson’s Disease: Insights from Molecular Docking Studies

“…Analgesic therapy for psoriasis, antidepressant, bone stimulant, Antiinflammatory [39][40][41][42] Other naturally occurring cannabinoids produced from Cannabis sativa are categorized into a variety of groups, including Cannabidiol (CBD), Cannabichromene (CBC), Cannabicyclol (CBL), Cannabitriol (CBT), Cannabielsoin (CBE), Cannabinol (CBN), and other unconventional types [43]. Cannabinoids interact with several receptors to exert their wide range of beneficial biological effects in the central nervous system and modulate the toxicity of ADassociated proteins.…”

Cannabidiol-loaded microparticles embedded in a porous hydrogel matrix for biomedical applications

“…The global CBD oil extract market was valued at US$ 7.94 billion in 2021 with a prospect of reaching US$ 37.74 billion in 2029 [ 12 ]. The increasing popularity of CBD may be attributed to its multiple medicinal properties, all of which have not yet been proven, including antiemetic, antioxidant [ 13 – 16 ], anticancer [ 9 , 17 , 18 ], regenerative [ 10 , 19 , 20 ], and anti-inflammatory [ 21 ] effects. CBD has been tested in therapies for cancer, epilepsy, pain, inflammation, and psychiatric disorders [ 8 ].…”