Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer

Jeong, Soyeon; Jo, Min Jee; Yun, Ho-Gyeong; Kim, Dae Yeong; Kim, Bo Ram; Kim, Jung Lim; Park, Seong Hye; Na, Yoo Jin; Jeong, Yoon-Su; Kim, Bu Gyeom; Ashktorab, Hassan; Smoot, Duane T.; Heo, Jun Young; Han, Jeongsu; Lee, Sun Il; Kim, Han Do; Kim, Dae Hyun; Oh, Sang Cheul; Lee, Dong Hoon

doi:10.1038/s41419-019-2001-7

Cited by 66 publications

(75 citation statements)

References 28 publications

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“…There are also other studies where cancer cells were cultured with 10% FCS and treated with CBD or other synthetic CBD-like molecules. The results of these studies showed that CBD (5-20 μg/mL) reduced the viability of cancer cells and also had effects on other survival variables [6][7][8]16]. The cell lines used in these studies being different to the ones used in our study, could account for the different results observed.…”

Section: Limitationsmentioning

confidence: 56%

Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum

Sainz-Cort¹,

Müller‐Sánchez

Espel

2020

BMC Res Notes

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Objective: Cannabinoids are able to reduce tumor growth in xenograft models, but their therapeutic potential as anti-cancer drugs in humans is unclear yet. In vitro studies of the effect of cannabinoids on cancer cells are often carried out in absence of serum or in low serum concentration (i.e. 0.5% serum), conditions that limit cellular growth and therefore can increase the response of cells to additional challenges such as the presence of cannabinoids. However, the tumor microenvironment can be teaming with growth factors. In this study we assessed the viability and proliferation of cancer cells treated with cannabidiol in presence of a serum concentration that commonly sustains cell growth (10% serum). Results: The results show that cannabidiol exerts a markedly different effect on the viability of the human HT-29 cancer cell line when cultured in presence of 0.5% serum in comparison to 10% serum, displaying a cytotoxic effect only in the former situation. In presence of 10% serum, no inhibitory effect of cannabidiol on DNA replication of HT-29 cells was detected, and a weak inhibition was observed for other cancer cell lines. These results indicate that the effect of cannabidiol is cell context-dependent being modulated by the presence of growth factors.

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Section: Limitationsmentioning

confidence: 56%

Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum

Sainz-Cort¹,

Müller‐Sánchez

Espel

2020

BMC Res Notes

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“…CBD is known for its anticancer activity [ 16 ] and is the abundant phytocannabinoid in the IGB strain (50.7%, Supplementary Table S1 ). Hence, we also examined the effect of CB1 and CB2 IA on CBD activity.…”

Section: Resultsmentioning

confidence: 99%

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

et al. 2021

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Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.

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“…We generated the mouse model of xenografted gastric cancer as previously described [ 30 ]. Briefly, AGS cells (10 7 cells) were subcutaneously injected into each mouse [ 34 , 35 ]. The mice were weighed twice a week.…”

Section: Methodsmentioning

confidence: 99%

Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

Kim

Jeena

Kim

et al. 2020

IJMS

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Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes.

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Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer

Cited by 66 publications

References 28 publications

Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum

Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

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