The antitumor activity of cannabidiol on lung cancer cell lines A549 and H1299: the role of apoptosis

Abstract

In the recent years, the application of new antitumor drugs has focused on the replacement of conventional chemotherapeutics with compounds derived from natural products. Cannabidiol (CBD) is one of the 113 cannabinoids derived from the plant Cannabis sativa and is characterized with complex and not entirely understood biological function. Unlike the other most abundant cannabinoid in Cannabis sativa -tetrahydrocannabinol, cannabidiol has low affinity to the endocannabinoid receptors and the manifestation of its activity does not appear to rely on the endocannabinoid system. Cannabidiol is used in the treatment of many diseases including some types of cancer. The aim of our study was to evaluate the cytotoxic activity of cannabidiol and its effect on the process of programmed cell death. This process is directly involved in the antitumor effect of many drugs. Two lung cancer cell lines, A549 expressing р53 and H1299-p53 negative, were used. Apoptosis was monitored by Anexin V assay and the activation of Caspase 3/7. We found that CBD treatment led to a dose-dependant apoptosis increase in p53 positive A549 cells. The level of apoptosis in p53 negative H1299 cells was much lower and did not seem to be dose dependent. However, the total cell viability was similar for the two cell lines, which was due to the increased necrosis observed in H1299 cells.

Antitumorigenic Effect of Cannabidiol in Lung Cancer: What Do We Know So Far?–A Mini Review

“…One study was a letter to the editor [29] . Overall, this review included nine studies [30][31][32][33][34][35][36][37][38] , which met the inclusion criteria we set. The study selection process is shown in Figure 1.…”

“…All included in vitro studies were assigned to Klimisch category 1. Eight out of nine studies received maximum score (18 points) as all criteria were met [30][31][32][33][35][36][37][38] . One study gained 16 points as it missed criteria 2 and 12 (purity of the test substance and positive controls included) [34] .…”

“…In a cohort of 157 lung cancer patients, the increased cannabinoid receptor expression in the primary tumor was associated with prolonged survival [ 38 ] . In a recent study included in this review, the authors observed that CBD induced apoptosis in A549 cells, which express p53 in a dose-dependent manner [ 33 ] . The effect was much less pronounced in H1299 cell line, which did not express p53, and no dose-response relationship was observed.…”

“…Todorova et al [33] CBD Bulgaria In vitro A549, H1299 CBD induces apoptosis in A549 cells which express p53 in a dose dependant manner;…”

Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges

“…To increase the understanding of CBD action, there is a growing body of in vitro and pre-clinical evidence for the effectiveness of CBD in slowing tumor growth and causing cancer cell death [ 11 , 12 , 13 , 14 , 15 ]. CBD is metabolized by the cytochrome P450 (CYP) family of enzymes in the liver, with CYP2C9, CYP2C19, and CYP3A4 responsible for most of its conversion to 7-OH-CBD [ 16 , 17 ].…”