Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8-O-(12-Aminododecanoyl)-8-O-Debutanoylthapsigargin

Zimmermann, Tomáš; Drašar, Pavel; Rimpelová, Silvie; Christensen, Søren Brøgger; Хрипач, В. А.; Jurášek, Michal

doi:10.3390/biom10121640

Cited by 11 publications

(10 citation statements)

References 36 publications

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“…Thus far, a large number of natural compounds have been identified to have anti-tumor effects. The action mechanisms of these compounds are varied, including inducement of endoplasmic reticulum stress and cell cycle arrest, inhibition of ATPase and protein synthesis, and promotion of apoptosis [ 30 , 31 , 32 , 33 , 34 ]. Ginsenosides, the main active ingredients in ginseng, have been suggested to have therapeutic effects on a variety of human diseases, such as senescence, hyperglycemia, hypertension, hypoimmunity, and cancer.…”

Section: Discussionmentioning

confidence: 99%

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Chen

Yang

2021

Molecules

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Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.

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Section: Discussionmentioning

confidence: 99%

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Chen

Yang

2021

Molecules

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“…Alternatively, PS can be modified by ligands increasing cell specificity of PS drugs [40,41]. Such active targeting can be achieved by modification with specific antibodies, nanobodies, affibodies, peptides, aptamers [42], androgens [43], or natural products such as sesquiterpene lactones and their derivatives [44][45][46]. Besides nanoparticles, liposomes are also a viable alternative for PS targeted delivery.…”

Section: Photodynamic Therapymentioning

confidence: 99%

Quo Vadis Advanced Prostate Cancer Therapy? Novel Treatment Perspectives and Possible Future Directions

et al. 2021

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Prostate cancer is a very common disease, which is, unfortunately, often the cause of many male deaths. This is underlined by the fact that the early stages of prostate cancer are often asymptomatic. Therefore, the disease is usually detected and diagnosed at late advanced or even metastasized stages, which are already difficult to treat. Hence, it is important to pursue research and development not only in terms of novel diagnostic methods but also of therapeutic ones, as well as to increase the effectiveness of the treatment by combinational medicinal approach. Therefore, in this review article, we focus on recent approaches and novel potential tools for the treatment of advanced prostate cancer; these include not only androgen deprivation therapy, antiandrogen therapy, photodynamic therapy, photothermal therapy, immunotherapy, multimodal therapy, but also poly(ADP-ribose) polymerase, Akt and cyclin-dependent kinase inhibitors.

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“…Sesquiterpenes were known to exhibit anti-cancer properties [16]. Currently, thapsigargin and trilobolide are leading sesquiterpene lactones in anticancer therapy [17,18]. It has been reported that costunolide possesses a variety of biological properties, such as anti-oxidant [19], anti-inflammatory [20], anti-allergic [21], neuroprotective [22], antimicrobial [23], anti-cancer [24], and bone remodeling [25] effects.…”

Section: Introductionmentioning

confidence: 99%

Costunolide, a Sesquiterpene Lactone, Suppresses Skin Cancer via Induction of Apoptosis and Blockage of Cell Proliferation

Lee

Cho

Lim

2021

IJMS

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Costunolide is a naturally occurring sesquiterpene lactone that demonstrates various therapeutic actions such as anti-oxidative, anti-inflammatory, and anti-cancer properties. Costunolide has recently emerged as a potential anti-cancer agent in various types of cancer, including colon, lung, and breast cancer. However, its mode of action in skin cancer remains unclear. To determine the anti-cancer potential of costunolide in skin cancer, human epidermoid carcinoma cell line A431 was treated with costunolide. A lactate dehydrogenase assay showed that costunolide diminished the viability of A431 cells. Apoptotic cells were detected by annexin V/propidium iodide double staining and Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay assay, and costunolide induced cell apoptosis via activation of caspase-3 as well as induction of poly-ADP ribose polymerase cleavage in A431 cells. In addition, costunolide elevated the level of the pro-apoptotic protein Bax while lowering the levels of anti-apoptotic proteins, including Bcl-2 and Bcl-xL. To address the inhibitory effect of costunolide on cell proliferation and survival, various signaling pathways, including mitogen-activated protein kinases, signal transducer and activator of transcription 3 (STAT3), nuclear factor κB (NF-κB), and Akt, were investigated. Costunolide activated the p38 and c-Jun N-terminal kinase pathways while suppressing the extracellular signal-regulated kinase (ERK), STAT3, NF-κB, and Akt pathways in A431 cells. Consequently, it was inferred that costunolide suppresses cell proliferation and survival via these signaling pathways. Taken together, our data clearly indicated that costunolide exerts anti-cancer activity in A431 cells by suppressing cell growth via inhibition of proliferation and promotion of apoptosis. Therefore, it may be employed as a potentially tumor-specific candidate in skin cancer treatment.

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Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8-O-(12-Aminododecanoyl)-8-O-Debutanoylthapsigargin

Cited by 11 publications

References 36 publications

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Quo Vadis Advanced Prostate Cancer Therapy? Novel Treatment Perspectives and Possible Future Directions

Costunolide, a Sesquiterpene Lactone, Suppresses Skin Cancer via Induction of Apoptosis and Blockage of Cell Proliferation

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