Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells

Durchschein, Christin; Hüfner, Antje; Rinner, Beate; Stallinger, Alexander; Deutsch, Alexander; Lohberger, Birgit; Bauer, Rudolf; Kretschmer, Nadine

doi:10.3390/molecules23112820

Cited by 16 publications

(16 citation statements)

References 47 publications

(64 reference statements)

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“…The present study identified that a high concentration of shikonin demonstrated characteristics of necrosis, whereas a low concentration demonstrated characteristics of apoptosis (data not shown). In spite of the large number of studies indicating that shikonin induces apoptosis in various human tumor cell lines (8,9,11), the molecular mechanism of the potential anti-glioma effect of shikonin is not completely understood.…”

Section: Discussionmentioning

confidence: 99%

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

et al. 2019

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Shikonin, a traditional Chinese medicine, has been identified as being capable of inducing apoptosis in various tumors, including glioma, and is thus considered to be a promising therapeutic agent for tumor therapy. However, little is known about the molecular mechanism of shikonin in glioma. The present study investigated the influence of shikonin on the proliferation and apoptosis of glioma cells U251 and U87MG and explored the potential molecular mechanisms. It was identified that shikonin was able to induce apoptosis in human glioma cells in a time- and dose-dependent manner, and a decreased expression level of cluster of differentiation (CD)147 was observed in shikonin-treated U251 and U87MG cells. Knockdown of CD147 inhibited U251 and U87MG cell growth, whereas CD147 overexpression enhanced cell growth and decreased shikonin-induced apoptosis. Additionally, an increased expression level of CD147 suppressed the elevated production of reactive oxygen species and mitochondrial membrane potential levels induced by shikonin. The data indicated that shikonin-induced apoptosis in glioma cells was associated with the downregulation of CD147 and the upregulation of oxidative stress. CD147 may be an optional target of shikonin-induced cell apoptosis in glioma cells.

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Section: Discussionmentioning

confidence: 99%

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

et al. 2019

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“…Besides, it inhibits cell proliferation and migration, and induces cell cycle arrest and apoptosis in murine melanoma B16F0 cells [626]. Another novel shikonin derivative, cyclopropylacetylshikonin, exhibits strong anti-tumor and pro-apoptotic effects in human melanoma WM164 and MUG-MEL2 cells [628]. In addition, drug delivery system is also developed to promote the intracellular delivery of shikonin.…”

Section: Shikoninmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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“…In addition, cyclopropylacetylshikonin, a structural analogue of acetylshikonin, suppressed the proliferation of melanoma cell lines (WM164 and MUG-Mel2). The mechanisms were associated with inducing caspase-dependent apoptosis, leading to doublestranded DNA breaks, and increasing the protein levels of cleaved Poly ADP-ribose polymerase (Durchschein et al 2018).…”

Section: Lung Cancermentioning

confidence: 99%

“…The mechanisms were associated with inducing caspase-dependent apoptosis, leading to double-stranded DNA breaks, and increasing the protein levels of cleaved Poly ADP-ribose polymerase (Durchschein et al. 2018 ).…”

Section: Pharmacologymentioning

confidence: 99%

Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review

Zhang

Bai

Zeng

et al. 2020

Pharmaceutical Biology

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Context: Acetylshikonin, a naphthoquinone derivative, is mainly extracted from some species of the family Boraginaceae, such as Lithospermum erythrorhizon Sieb. et Zucc., Arnebia euchroma (Royle) Johnst., and Arnebia guttata Bunge. As a bioactive compound, acetylshikonin has attracted much attention because of its broad pharmacological properties. Objective: This review provides a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of acetylshikonin focussing on its mechanisms on the basis of currently available literature. Methods: The information of acetylshikonin from 1977 to 2020 was collected using major databases including Elsevier, Scholar, PubMed, Springer, Web of Science, and CNKI. Acetylshikonin, pharmacology, toxicity, pharmacokinetics, and naphthoquinone derivative were used as key words. Results: According to emerging evidence, acetylshikonin exerts a wide spectrum of pharmacological effects such as anticancer, anti-inflammatory, lipid-regulatory, antidiabetic, antibacterial, antifungal, antioxidative, neuroprotective, and antiviral properties. However, only a few studies have reported the adverse effects of acetylshikonin, with respect to reproductive toxicity and genotoxicity. Pharmacokinetic studies demonstrate that acetylshikonin is associated with a wide distribution and poor absorption. Conclusions: Although experimental data supports the beneficial effects of this compound, acetylshikonin cannot be considered as a therapy drug without further investigations, especially, on the toxicity and pharmacokinetics.

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Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells

Cited by 16 publications

References 47 publications

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review

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