β-2-himachalen-6-ol protects against skin cancer development <i>in vitro</i> and <i>in vivo</i>

Daaboul, Hamid Elia; Daher, Costantine F.; Taleb, Robin I.; Boulos, Joelle C.; Bodman‐Smith, Kikki; Boukamp, Petra; Shebaby, Wassim N.; Dagher, Carol; El‐Sibai, Mirvat; Mroueh, Mohamad

doi:10.1111/jphp.12796

Cited by 15 publications

(12 citation statements)

References 49 publications

(123 reference statements)

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“…Moreover, it has been reported that the antitumor activity of these compounds was associated with the induction of apoptosis through caspase-3 activation and the inhibition of DNA. [15][16][17][18] Meanwhile, the literature survey revealed that semicarbazone and thiosemicarbazone derivatives have demonstrated great promise in pharmacological and industrial chemistry. [19] Also, they have been widely used as useful intermediates to produce heterocyclic compounds (such as thiazoles and 4-thiazolidinones) and as ligands in metal-complexes synthesis because of their excellent chemical properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

et al. 2022

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Herein, we report the synthesis of a novel series of βhimachalene derivatives, including semicarbazones, thiosemicarbazones, and thiazoles. The structures of these compounds were elucidated by NMR, IR, and HRMS analysis methods. The in vitro antitumor activity of these compounds was evaluated by the MTT assay against four human cancer cell lines, such as fibrosarcoma (HT-1080), breast adenocarcinoma (MCF-7 and MDA-MB-231), and lung carcinoma (A-549), and the results indicated that all compounds showed moderate to significant cytotoxic activities against all cancer cell lines with IC 50 values ranging from 7.19 � 0.30 to 50 μM. The mechanism of action of the most cytotoxic compounds 2 b and 7 b suggested that they induced apoptosis through caspase-3/7 activation, and elicited G2/M-phase arrest with the loss of mitochondrial membrane potential in HT-1080 cells. The molecular docking showed that compounds 2 b and 7 b activated the caspase-3 by forming a stable protein-ligand complex.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

et al. 2022

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“…In addition, earlier work in our lab showed that β-2-himachalene-6-ol, an isomer of 7-HC, isolated from wild carrot demonstrated potent anticancer activity against several human and murine cancer cell lines 22,23 . β-2-Himachalene-6-ol was also found to exhibit significant anti-tumor promoting effect against DMBA/TPA skin carcinogenesis and dimethylhydrazine-induced colon carcinogenesis in mice 24 .…”

Section: Discussionmentioning

confidence: 96%

In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani

Elias

Shebaby

Nehme

et al. 2019

Sci Rep

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Cedrus libani is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce C. libani oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC 50 8.1 μg/mL) and colon (HT-29, IC 50 10.1 μg/mL; Caco-2, IC 50 9.9 μg/mL) with ovarian (Sk-OV-3, IC 50 > 50 μg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8–10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy.

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“…More recently, β‐2‐himachalen‐6‐ol ((Figure 1): A‐1) and 2‐himachelen‐7‐ol ((Figure 1): A‐2) showed promising cytotoxic activity against B16‐F‐10, Caco‐2, MB‐MDA‐231 and A‐549 cells. In the same way, the mechanism of action study showed that these products induced apoptosis through the activation of caspase‐3 in renal cell carcinoma (HaCaT‐ras) ((Figure 1): A‐1) or ((Figure 1): A‐2), associated with the ability to interact with DNA [6–8] …”

Section: Introductionmentioning

confidence: 87%

“…In the same way, the mechanism of action study showed that these products induced apoptosis through the activation of caspase-3 in renal cell carcinoma (HaCaT-ras) ((Figure 1): A-1) or ((Figure 1): A-2), associated with the ability to interact with DNA. [6][7][8] Nowadays, heterocyclic compounds carrying oxygen and nitrogen are an important class of compounds with interesting biological and pharmacological activities, due to their similarity with various bioactive molecules of natural origin. [9][10][11] Among these compounds, substituted thiazolidin-4-ones mediated significant antiproliferative effects, studies concerning structure-activity relationships have shown that the cytotoxic potency of compounds was highly dependent on the types and patterns of N-substitution on the thiazolidin-4-one ring.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Biological and Computational Assessment of New Thiazolidin‐4‐one Derivatives as Potential Anticancer Agents Through the Apoptosis Pathway

et al. 2022

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A variety of novel thiazolidin‐4‐one himachalene derivatives were designed and synthesized through hetero‐cyclization of thiosemicarbazone analogs that have previously exhibited strong anticancer activity. The synthesized products 2 a–4 f were completely characterized by 1H NMR, 13C NMR, IR, and HRMS and were later submitted for in vitro evaluation of their anticancer activity and cytotoxicity on a panel of four human cancer cell lines ( i.eHT‐1080, MCF‐7, A‐549, and MDA‐MB‐231). Most of the evaluated compounds showed potent antiproliferative activities against the four human cancer cell lines with tested IC50 values ranging from 5.25±0.32 to 9.26±0.73 μM. The mechanism of action revealed that compounds 2 b and 4 b induced caspase‐3/7‐activated apoptosis and cell cycle arrest in the G0/G1 stage in HT‐1080 and A‐549 cells. Furthermore, molecular docking studies were conducted to evaluate the binding affinities and the possible binding modes of the top‐performing compounds 2 b and 4 b. This was later supported by Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis predicting their prospective pharmacological profiles. The outcome of this study supports the validity of our strategy and presents 2 b and 4 b as a pattern for the discovery of novel cancer therapeutics.

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β-2-himachalen-6-ol protects against skin cancer development in vitro and in vivo

Abstract: In conclusion, HC treatment induced cell cycle arrest (low dose) and promoted apoptosis partly via inhibition of the MAPK/ERK and PI3K/AKT pathways with no significant toxicity to laboratory mice.

Cited by 15 publications

References 49 publications

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti‐Proliferative and Mechanistic Analyses and Molecular Docking Studies

In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani

Design, Synthesis, Biological and Computational Assessment of New Thiazolidin‐4‐one Derivatives as Potential Anticancer Agents Through the Apoptosis Pathway

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