Thapsigargin—From Traditional Medicine to Anticancer Drug

Jaskulska, Agata; Janecka, Anna; Gach-Janczak, Katarzyna

doi:10.3390/ijms22010004

Cited by 83 publications

(53 citation statements)

References 67 publications

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“…This stress response promoted the further expansion of MDSCs, although it shortened their lifespan (Condamine et al, 2014). Thapsigargin, a class of highly oxidized sesquiterpene lactones isolated from the Mediterranean plant Thapsia garganica, has been recognized as an ER stressor because of its irreversible inhibition of the sarcoplasmic/ER Ca 2+ -ATPase pump which pump Ca 2+ ions from the cytoplasm into ER (Jaskulska et al, 2020). Thapsigargin inhibited Ca 2+ transport from the cytosol to ER, declining Ca 2+ concentration in the ER to lead ER dysfunction and eventually trigger ER stress.…”

Section: Er Stressmentioning

confidence: 99%

Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment

Jihu

et al. 2021

Front. Cell Dev. Biol.

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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells generated in various pathologic conditions, which have been known to be key components of the tumor microenvironment (TME) involving in tumor immune tolerance. So MDSCs have been extensively researched recently. As its name suggests, immunosuppression is the widely accepted function of MDSCs. Aside from suppressing antitumor immune responses, MDSCs in the TME also stimulate tumor angiogenesis and metastasis, thereby promoting tumor growth and development. Therefore, altering the recruitment, expansion, activation, and immunosuppression of MDSCs could partially restore antitumor immunity. So, this view focused on the favorable TME conditions that promote the immunosuppressive effects of MDSCs and contribute to targeted therapies with increased precision for MDSCs.

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Section: Er Stressmentioning

confidence: 99%

Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment

Jihu

et al. 2021

Front. Cell Dev. Biol.

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“…Since one of the biggest obstacles seen with many existing anticancer treatments is the selective anticancer effect. For example, a potent cytotoxic effect of thapsigargin, one of sesquiterpene lactones was considered as a novel candidate for anti-cancer agent but it hampered due to high toxicity to normal cells [66]. The mechanism for this selective anti-cancer effect was examined only in our results: (1) costunolide selectively causes changes in the Bcl-2 family, the signaling process involved in apoptosis, and caspase-3 activity in only A431 cells not HEKn.…”

Section: Discussionmentioning

confidence: 81%

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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“…Additionally, JQ-FT is an antileukemic prodrug established by a conjugation of a thapsigargin derivative and folic acid. These prodrugs represent an efficient way to overcome thapsigargin cytotoxicity and provide targeted cancer therapy [764].…”

Section: Safety Aspects Of Natural Products In Cancer Managementmentioning

confidence: 99%

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

et al. 2021

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Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

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Thapsigargin—From Traditional Medicine to Anticancer Drug

Cited by 83 publications

References 67 publications

Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment

Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment

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

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

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