Structure-dependent inhibitory effects of synthetic cannabinoids against 12-<i>O</i>-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice

Nakajima, Jun; Nakae, Dai; Yasukawa, Ken

doi:10.1111/jphp.12082

Cited by 15 publications

(13 citation statements)

References 26 publications

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“…The effects of TPA on keratin reorganization in PANC-1 cells and on the underlying mechanisms of their migratory properties were the foci of the present study. Even though TPA has long been known to promote tumorigenesis and PKC activator (Blumberg, 1988; Nakajima et al ., 2013), its influence on keratin phosphorylation and reorganization had not previously been investigated.…”

Section: Discussionmentioning

confidence: 99%

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12-O-Tetradecanoylphorbol-13-Acetate Induces Keratin 8 Phosphorylation and Reorganization via Expression of Transglutaminase-2

Lee

Park

Kim

et al. 2014

Biomolecules & Therapeutics

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The stiffness of cancer cells is attributable to intermediate filaments such as keratin. Perinuclear reorganization via phosphorylation of specific serine residue in keratin is implicated in the deformability of metastatic cancer cells including the human pancreatic carcinoma cell line (PANC-1). 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a potent tumor promoter and protein kinase C (PKC) activator. However, its effects on phosphorylation and reorganization of keratin 8 (K8) are not well known. Therefore, we examined the underlying mechanism and effect of TPA on K8 phosphorylation and reorganization. TPA induced phosphorylation and reorganization of K8 and transglutaminase-2 (Tgase-2) expression in a time- and dose-dependent manner in PANC-1 cells. These effects peaked after 45 min and 100 nM of TPA treatment. We next investigated, using cystamine (CTM), Tgase inhibitor, and Tgase-2 gene silencing, Tgase-2’s possible involvement in TPA-induced K8 phosphorylation and reorganization. We found that Tgase-2 gene silencing inhibited K8 phosphorylation and reorganization in PANC-1 cells. Tgase-2 gene silencing, we additionally discovered, suppressed TPA-induced migration of PANC-1 cells and Tgase-2 overexpression induced migration of PANC-1 cells. Overall, these results suggested that TPA induced K8 phosphorylation and reorganization via Tgase-2 expression in PANC-1 cells.

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Section: Discussionmentioning

confidence: 99%

“…12-O-Tetradecanoylphorbol-13-acetate (TPA), also commonly known as phorbol-12-myristate-13-acetate (PMA), is a diester of phorbol and a potent tumor promoter often employed in skin cancer models (Nakajima et al ., 2013). Via the PKC/AP-1 pathway, TPA induces cancer cell invasion (Xu et al ., 2013).…”

Section: Introductionmentioning

confidence: 99%

12-O-Tetradecanoylphorbol-13-Acetate Induces Keratin 8 Phosphorylation and Reorganization via Expression of Transglutaminase-2

Lee

Park

Kim

et al. 2014

Biomolecules & Therapeutics

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“…Mixed CB1 and CB2 synthetic cannabinoids JWH-018, JWH-122, and JWH-210 demonstrate effective effects in topical application against both carcinogenesis and ear inflammation on a TPA-induced mouse model, hinting at interconnection and interferences between cancer development and inflammation, influenced by CB1 and CB2 [183].…”

Section: Non-melanoma Cancersmentioning

confidence: 97%

Cannabinoids in the Pathophysiology of Skin Inflammation

et al. 2020

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Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.

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“…Although presently absent within otolaryngology literature, there is encouraging in vitro and in vivo data demonstrating significant antineoplastic potential of the ESS within a wide variety of cancer models . The ENT‐related tumors with data demonstrating the potential antineoplastic activity of cannabinoids include oropharyngeal and tongue cancer, thyroid cancer, lymphoma, basal cell, squamous cell, and melanoma . Using a mouse model, Shi et al demonstrated a strong antitumoral effect on anaplastic thyroid cancer cell lines.…”

Section: Potential Therapies For the Otolaryngic Patientmentioning

confidence: 99%

“…34,38,109,116 The ENT-related tumors with data demonstrating the potential antineoplastic activity of cannabinoids include oropharyngeal and tongue cancer, thyroid cancer, lymphoma, basal cell, squamous cell, and melanoma. 5,7,27,36,38,68,79,107,[117][118][119][120][121][122][123][124][125][126][127] Using a mouse model, Shi et al demonstrated a strong antitumoral effect on anaplastic thyroid cancer cell lines. In addition to the direct effects observed, ESS agonism was also shown to increase paclitaxel induced apoptosis by two-fold via an unknown synergistic mechanism.…”

Section: Painmentioning

confidence: 99%

Therapeutic Cannabis and Endocannabinoid Signaling System Modulator Use in Otolaryngology Patients

Bryant

Daniels

Cognetti

et al. 2018

Laryngoscope Investig Oto

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Objectives1) review benefits and risks of cannabis use, with emphasis on otolaryngic disease processes; 2) define and review the endocannabinoid signaling system (ESS); and 3) review state and federal regulations for the use and research of cannabis and ESS modulators.MethodsThis manuscript is a review of the current literature relevant to the stated objectives.ResultsCannabis (marijuana) use is increasing. It is the most widely used illicit substance in the world. There is increasing interest in its therapeutic potential due to changing perceptions, new research, and legislation changes controlling its use. The legal classification of cannabis is complicated due to varied and conflicting state and federal laws. There are currently two synthetic cannabinoid drugs that are FDA approved. Current indications for use include chemotherapy‐related nausea and vomiting, cachexia, and appetite loss. Research has demonstrated potential benefit for use in many other pathologies including pain, inflammatory states, and malignancy. Data exists demonstrating potential antineoplastic benefit in oral, thyroid, and skin cancers.ConclusionsESS modulators may play both a causal and therapeutic role in several disorders seen in otolaryngology patients. The use of cannabis and cannabinoids is not without risk. There is a need for further research to better understand both the adverse and therapeutic effects of cannabis use. With increasing rates of consumption, elevated public awareness, and rapidly changing legislation, it is helpful for the otolaryngologist to be aware of both the adverse manifestations of use and the potential therapeutic benefits when talking with patients.

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Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice

Cited by 15 publications

References 26 publications

12-O-Tetradecanoylphorbol-13-Acetate Induces Keratin 8 Phosphorylation and Reorganization via Expression of Transglutaminase-2

12-O-Tetradecanoylphorbol-13-Acetate Induces Keratin 8 Phosphorylation and Reorganization via Expression of Transglutaminase-2

Cannabinoids in the Pathophysiology of Skin Inflammation

Therapeutic Cannabis and Endocannabinoid Signaling System Modulator Use in Otolaryngology Patients

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