Cannabidiol Regulates PPARγ-Dependent Vesicle Formation as well as Cell Death in A549 Human Lung Cancer Cells

Abstract

Extracts of phytocannabinoids from Cannabis sativa have been studied for therapeutic purposes. Although nonpsychoactive CBD has been studied as a promising anticancer drug because it induces apoptosis in many cancer cells, it is also known to induce several physiological changes. In this study, we clarify the functional role it plays in the morphological characteristics of intracellular vesicle formation as well as apoptosis in A549 human lung cancer cells. CBD treatment shows growth inhibition at concentrations above 20 μM, but FACS analysis shows low efficacy in terms of cell death. Microscopic observations suggest that multiple vesicles were detected in the cytoplasmic region of CBD-treated A549 cells. CBD treatment upregulates apoptosis-related proteins, such as p53, PARP, RIP1, RIP3, Atg12, and Beclin, indicating that CBD regulates several types of cell death. CBD treatment also induced E-cadherin, PPARγ, clathrin, β-adaptin, and Tsg101, also known to be cellular-differentiation inducers or vesicle-formation components. Treatment combining CBD with GW9662, a PPARγ inhibitor, reduced CBD-induced cytoplasmic vesicle formation. This indicates that PPARγ regulates the vesicle-formation mechanism. However, CBD-treated E-cad KO clones did not show this regulatory mechanism. These results elucidate the pharmacological and molecular networks associated with CBD in PPARγ-dependent vesicle formation and the induction of apoptosis.

Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells

“…To determine this, we first investigated whether CBD has any particular effects on NSCLC cell lines with diverse genetic backgrounds such as A549 cells (KRAS mutation, P53 wide-type), NCI-H2228 (EML4-ALK variant 3, P53 Q331 * mutation) and HCC-827 (EGFR exon19 deletion mutant, inactivation P53 mutation). A study concluded that CBD treatment regulates several types of cell death via upregulating apoptosis-related proteins, such as p53 in A549 (45). Similarly, our analysis revealed that A549 cells were more sensitive to CBD treatment compared to other cell types, presumably attributable to their p53 wild-type state.…”

Synergistic effects of cannabidiol and cytokine-induced killer cells via the modulation of TRPV2 channel and intracellular p-ERK 1/2 expression on non-small cell lung cancer cells

“…To determine this, we first investigated whether CBD has any particular effects on NSCLC cell lines with diverse genetic backgrounds such as A549 cells (KRAS mutation, P53 wide-type), NCI-H2228 (EML4-ALK variant 3, P53 Q331* mutation) and HCC-827 (EGFR exon19 deletion mutant, inactivation P53 mutation). A study concluded that CBD treatment regulates several types of cell death via upregulation apoptosis-related proteins, such as p53 in A549 [31]. Similarly, our analysis revealed that A549 cells were more sensitive to CBD treatment compared to other cell types, presumably attributable to their p53 wild-type state.…”

Metallothionein Family Proteins as Regulators of Zinc Ions Synergistically Enhance the Anticancer Effect of Cannabidiol in Human Colorectal Cancer Cells

“…Cannabinoids can interact with their receptors or proteins via cellular pathways, thus affecting the development/progression of diseases, including cancer [35]. Our previous study suggested that CBD shows anticancer activity by inducing PPAR-γ-dependent cytoplasmic vesicles in human lung cancer cells and colorectal cancer cells [36,37]. This biological activity was also observed in colorectal cancer cells, indicating the anticancer effects of cannabinoids on various cancer types.…”