The labdane diterpene sclareol (labd-14-ene-8, 13-diol) induces apoptosis in human tumor cell lines and suppression of tumor growth in vivo via a p53-independent mechanism of action

Mahaira, Louisa G.; Tsimplouli, Chrisiida; Sakellaridis, Nikolaos; Alevizopoulos, Konstantinos; Demetzos, Costas; Han, Zhiyong; Pantazis, Panayotis; Dimas, Konstantinos

doi:10.1016/j.ejphar.2011.04.065

Cited by 40 publications

(27 citation statements)

References 42 publications

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“…The labdane-type diterpene sclareol, which is used today as a certified drug, has antitumor activity against human breast cancer cell lines and enhances the activity of known anticancer drugs (Dimas et al, 2006). Sclareol is activated through a p53-independent mechanism that targets the G 1 phase of the cell cycle and therefore apoptosis of human cancer cells is induced through the activation of caspases (Mahaira et al, 2011). …”

Section: Biological Functionsmentioning

confidence: 99%

Genus Cistus: a model for exploring labdane-type diterpenes' biosynthesis and a natural source of high value products with biological, aromatic, and pharmacological properties

et al. 2014

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The family Cistaceae (Angiosperm, Malvales) consists of 8 genera and 180 species, with 5 genera native to the Mediterranean area (Cistus, Fumara, Halimium, Helianthemum, and Tuberaria). Traditionally, a number of Cistus species have been used in Mediterranean folk medicine as herbal tea infusions for healing digestive problems and colds, as extracts for the treatment of diseases, and as fragrances. The resin, ladano, secreted by the glandular trichomes of certain Cistus species contains a number of phytochemicals with antioxidant, antibacterial, antifungal, and anticancer properties. Furthermore, total leaf aqueous extracts possess anti-influenza virus activity. All these properties have been attributed to phytochemicals such as terpenoids, including diterpenes, labdane-type diterpenes and clerodanes, phenylpropanoids, including flavonoids and ellagitannins, several groups of alkaloids and other types of secondary metabolites. In the past 20 years, research on Cistus involved chemical, biological and phylogenetic analyses but recent investigations have involved genomic and molecular approaches. Our lab is exploring the biosynthetic machinery that generates terpenoids and phenylpropanoids, with a goal to harness their numerous properties that have applications in the pharmaceutical, chemical and aromatic industries. This review focuses on the systematics, botanical characteristics, geographic distribution, chemical analyses, biological function and biosynthesis of major compounds, as well as genomic analyses and biotechnological approaches of the main Cistus species found in the Mediterranean basin, namely C. albidus, C. creticus, C. crispus, C. parviflorus, C. monspeliensis, C. populifolius, C. salviifolius, C. ladanifer, C. laurifolius, and C. clusii.

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Section: Biological Functionsmentioning

confidence: 99%

Genus Cistus: a model for exploring labdane-type diterpenes' biosynthesis and a natural source of high value products with biological, aromatic, and pharmacological properties

et al. 2014

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“…The anticancer activity of sclareol in vivo has been assessed using human colon cancer xenograft/mouse models. It was observed that sclareol arrested the growth of p53-deficient human colon cancer cells and subsequently induced apoptosis through the activation of caspases-8 and -9 in vivo (13). In another study, sclareol was reported to exhibit an anticancer effect against MN1 and MDD2 human breast cancer cell lines derived from the MCF-7 parental cell line.…”

Section: Discussionmentioning

confidence: 97%

Sclareol, a plant diterpene, exhibits potent antiproliferative effects via the induction of apoptosis and mitochondrial membrane potential loss in osteosarcoma cancer cells

Wang

et al. 2015

Molecular Medicine Reports

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The objective of the current study was to evaluate the antiproliferative activity of sclareol against MG63 osteosarcoma cells. A 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay was used to evaluate the cell viability of cells following treatment with sclareol. The extent of cell death induced by sclareol was evaluated using a lactate dehydrogenase (LDH) assay. The effect of sclareol on cell cycle progression and mitochondrial membrane potential (ΛΨm) was evaluated with flow cytometry using the DNA‑binding fluorescent dyes propidium iodide and rhodamine‑123, respectively. Fluorescence microscopy was used to detect the morphological changes in the MG63 osteosarcoma cancer cells and the appearance of apoptotic bodies following sclareol treatment. The results revealed that sclareol induced dose‑ and time‑dependent growth inhibition of MG63 cancer cells with an IC50 value of 65.2 µM following a 12‑h incubation. Furthermore, sclareol induced a significant increase in the release of LDH from MG63 cell cultures, which was much more pronounced at higher doses. Fluorescence microscopy revealed that sclareol induced characteristic morphological features of apoptosis and the appearance of apoptotic bodies. Flow cytometry revealed that sclareol induced G1‑phase cell cycle arrest, which showed significant dose‑dependence. Additionally, sclareol induced a progressive and dose‑dependent reduction in the ΛΨm. In summary, sclareol inhibits the growth of osteosarcoma cancer cells via the induction of apoptosis, which is accompanied by G1‑phase cell cycle arrest and loss of ΛΨm.

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“…), which is isolated from Salvia officinalis , is widely used in the food and cosmetic industries as a fragrance . Sclareol has been known to have many biological activities, such as antioxidation, antifungal, anticancer, antimicrobial, anti‐inflammatory, and anticholinesterase activity . However, the ability of sclareol to inhibit skin photoaging has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

“…6 Sclareol has been known to have many biological activities, such as antioxidation, antifungal, anticancer, antimicrobial, anti-inflammatory, and anticholinesterase activity. [7][8][9][10][11] However, the ability of sclareol to inhibit skin photoaging has not yet been reported. Therefore, the efficacy of sclareol to inhibit UVB-induced photoaging in a human dermal fibroblast cell line (Hs68) and a reconstructed human epidermis 3D skin model (RHE) was evaluated in this study.…”

Section: Introductionmentioning

confidence: 99%

Sclareol isolated from Salvia officinalis improves facial wrinkles via an antiphotoaging mechanism

Park

Kyung-Eun

Jung

et al. 2016

J of Cosmetic Dermatology

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The labdane diterpene sclareol (labd-14-ene-8, 13-diol) induces apoptosis in human tumor cell lines and suppression of tumor growth in vivo via a p53-independent mechanism of action

Cited by 40 publications

References 42 publications

Genus Cistus: a model for exploring labdane-type diterpenes' biosynthesis and a natural source of high value products with biological, aromatic, and pharmacological properties

Genus Cistus: a model for exploring labdane-type diterpenes' biosynthesis and a natural source of high value products with biological, aromatic, and pharmacological properties

Sclareol, a plant diterpene, exhibits potent antiproliferative effects via the induction of apoptosis and mitochondrial membrane potential loss in osteosarcoma cancer cells

Sclareol isolated from Salvia officinalis improves facial wrinkles via an antiphotoaging mechanism

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