Effects of tetrahydrocannabinols on human oral cancer cell proliferation, apoptosis, autophagy, oxidative stress, and DNA damage

Semlali, Abdelhabib; Beji, Sarra; Ajala, Ikram; Rouabhia, Mahmoud

doi:10.1016/j.archoralbio.2021.105200

Cited by 27 publications

(42 citation statements)

References 43 publications

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“…Briefly, Ca9-22 and GMSM-K cells were seeded into 12-well plates at the density of 3 x 10 5 cells/well, cultured overnight and then exposed to different concentrations of rapamycin (from 0.1 to 100 µM) for 24 h. After incubation, the culture medium was replaced with a new one containing MTT solution of 5 mg/ml in PBS for 3 h at 37°C in the dark, as described by Semlali and al. previously ( 13 , 14 ). The cells were incubated for 15 min in 1 ml HCl 0.05 N-isopropanol solution to lyse the cells and release the formed formazan.…”

Section: Methodsmentioning

confidence: 95%

Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways

et al. 2022

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Treatment of oral cancer is based exclusively on surgery combined with or without chemotherapy. However, it has several side effects. Targeting a new, more effective therapy has become an urgent matter. The purpose of this study was to evaluate the anti-tumor activity of rapamycin in oral cancer and its mechanism of action. Human gingival carcinoma cells were stimulated with different concentrations of rapamycin to assess proliferation, colony formation, cell migration, as well as apoptosis, and autophagy. The expression of proteins involved in the cell cycle (cyclin D1, p15, p21, p27) and autophagy, as well as that of oncogenes and tumor suppressor genes, were determined by quantitative PCR. The signaling pathways were evaluated by Western blotting. Our results show that rapamycin has a selective effect at a low dose on cancer cell growth/survival. This was confirmed by low colony formation and the inhibition of cell migration, while increasing cell apoptosis by activating caspase-9 and -3. Rapamycin promoted cell autophagy and increased mitochondrial oxidative stress by being involved in DNA damage in the exposed cells. Finally, rapamycin exhibits potent anti-oral cancer properties through inhibition of several cancer-promoting pathways (MAPK, NF-κB, and Wnt/beta-catenin). These results indicate that rapamycin could be a potential agent for the treatment of oral cancer and for a prevention strategy.

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Section: Methodsmentioning

confidence: 95%

Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways

et al. 2022

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“…The human oral cancer cell line Ca9–22 cells were cultured at 37 °C and 5% CO 2 in RPMI-1640 medium (Thermo Fisher Scientific, Burlington, ON, Canada), supplemented with L-glutamine, 5% fetal bovine serum (FBS, Gibco) provided by the same company, and 1% penicillin/streptomycin solution (Sigma-Aldrich, Oakville, ON, Canada). Cell proliferation was bi-evaluated using two MTT and LDH tests as described by Semlali et al 2021 [ 35 , 36 ] and Contant et al 2021 [ 37 ]. For the MTT assay, 10 5 Ca9-22 cells per well containing the sample were seeded in 24-well plates for 24 h. After adhesion and growth of the cells, the culture medium is replaced by a new one containing a solution of MTT at 5 mg∙ml −1 in PBS and left for 3 h at 37 °C in the dark.…”

Section: Methodsmentioning

confidence: 99%

“…LDH assay was realized by the LDH Cytotoxicity Detection Kit from Roche, which allows to directly quantify the cell death in culture based on the measurement of lactate dehydrogenase released into growth media. As described in our previous work [ 35 , 36 ], 10 5 cells per well were seeded in 24-well plates containing NPX/pHEMA and NPX/pHPMA with different compositions. After adhesion for 24 h, 50 μL of each supernatant was transferred in triplicate into a 96-well plate and supplemented with 50 μL reconstituted substrate mixture.…”

Section: Methodsmentioning

confidence: 99%

Naproxen-Loaded Poly(2-hydroxyalkyl methacrylates): Preparation and Drug Release Dynamics

et al. 2022

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Poly(2-hydroxyethylmethacrylate)/Naproxen (NPX/pHEMA) and poly (2-hydroxypropyl methacrylate)/Naproxen (NPX/pHPMA) composites with different NPX content were prepared in situ by free radical photopolymerization route. The resulted hybrid materials were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning Electron microscopy (SEM), and X-ray diffraction (XRD). These composites have been studied as drug carrier systems, in which a comparison of the in vitro release dynamic of NPX between the two drug carrier systems has been conducted. Different factors affecting the performance of the release dynamic of this drug, such as the amount of Naproxen incorporated in the drug carrier system, the pH of the medium and the degree of swelling, have been investigated. The results of the swelling study of pHEMA and pHPMA in different media pHs revealed that the diffusion of water molecules through both polymer samples obeys the Fickian model. The “in vitro” study of the release dynamic of Naproxen from NPX/pHEMA and NPX/pHPMA drug carrier systems revealed that the higher percentage of NPX released was obtained from each polymer carrier in neutral pH medium, and the diffusion of NPX trough these polymer matrices also obeys the Fickian model. It was also found that the less the mass percent of NPX in the composites, the better its release will be. The comparison between the two drug carrier systems revealed that the pHEMA leads to the best performance in the release dynamic of NPX. Regarding Naproxen solubility in water, the results deducted from the “in vitro” study of NPX/pHEMA10 and NPX/pHPMA10 drug carrier systems revealed a very significant improvement in the solubility of NPX in media pH1 (2.33 times, 1.43 times) and 7 (3.32 times, 2.60 times), respectively, compared to those obtained by direct dissolution of Naproxen powder.

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“…Indeed, in one relative potency study, ∆8THC was shown to inhibit DNA synthesis more strongly and for a longer duration than other cannabinoids including ∆9THC [38]. Whilst this suggests an anti-cancer action for ∆8THC derivatives [36,37,39,40], its effects in vivo may be to potentiate carcinogenesis by interfering with DNA, RNA, and key nucleoprotein metabolism and DNA maintenance pathways [37,38]. As it has been shown long ago that the genotoxic moiety of cannabinoids resides in their central olevitol nucleus core structure [41,42], it is entirely possible that the described genotoxicity of many cannabinoids [13,43] is actually a class effect pertaining broadly to numerous cannabinoid derivates.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study

Reece

Hulse

2022

IJERPH

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The use of Δ8THC is increasing at present across the USA in association with widespread cannabis legalization and the common notion that it is “legal weed”. As genotoxic actions have been described for many cannabinoids, we studied the cancer epidemiology of Δ8THC. Data on 34 cancer types was from the Centers for Disease Control Atlanta Georgia, substance abuse data from the Substance Abuse and Mental Health Services Administration, ethnicity and income data from the U.S. Census Bureau, and cannabinoid concentration data from the Drug Enforcement Agency, were combined and processed in R. Eight cancers (corpus uteri, liver, gastric cardia, breast and post-menopausal breast, anorectum, pancreas, and thyroid) were related to Δ8THC exposure on bivariate testing, and 18 (additionally, stomach, Hodgkins, and Non-Hodgkins lymphomas, ovary, cervix uteri, gall bladder, oropharynx, bladder, lung, esophagus, colorectal cancer, and all cancers (excluding non-melanoma skin cancer)) demonstrated positive average marginal effects on fully adjusted inverse probability weighted interactive panel regression. Many minimum E-Values (mEVs) were infinite. p-values rose from 8.04 × 10−78. Marginal effect calculations revealed that 18 Δ8THC-related cancers are predicted to lead to a further 8.58 cases/100,000 compared to 7.93 for alcoholism and −8.48 for tobacco. Results indicate that between 8 and 20/34 cancer types were associated with Δ8THC exposure, with very high effect sizes (mEVs) and marginal effects after adjustment exceeding tobacco and alcohol, fulfilling the epidemiological criteria of causality and suggesting a cannabinoid class effect. The inclusion of pediatric leukemias and testicular cancer herein demonstrates heritable malignant teratogenesis.

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Effects of tetrahydrocannabinols on human oral cancer cell proliferation, apoptosis, autophagy, oxidative stress, and DNA damage

Cited by 27 publications

References 43 publications

Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways

Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways

Naproxen-Loaded Poly(2-hydroxyalkyl methacrylates): Preparation and Drug Release Dynamics

Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study

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