Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization

Dyshlovoy, Sergey A.; Hauschild, Jessica; Amann, Kerstin; Tabakmakher, Ksenia M; Venz, Simone; Walther, Reinhard; Guzii, Alla G.; Makarieva, Tatiana N.; Shubina, Larisa K.; Fedorov, Sergey N.; Stonik, Valentin A.; Bokemeyer, Carsten; Balabanov, Stefan; Honecker, Friedemann; Amsberg, Gunhild von

doi:10.18632/oncotarget.4175

Cited by 63 publications

(90 citation statements)

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“…Western blotting was performed as described before . Total protein extracts (20–30 µg/sample) were subjected to electrophoresis in SDS‐polyacrylamide gels at 120 V, and transferred from gel to a 0.2 µm pore PVDF membrane.…”

Section: Methodsmentioning

confidence: 99%

“…The medium was changed with medium containing FrA (1 µM). After 48 h of incubation cells were fixed and permeabilized as described before . After washing with PBS, samples were treated with 1: 400 rabbit anti‐LC3B‐I/II antibody solution (in 0.1% (w/v) NaN 3 ; 0.2% (w/v) BSA in PBS, pH 7.4) overnight at 4°C, washed with PBS and incubated with secondary anti‐rabbit Alexa Fluor 488‐conjugated antibody solution in PSB for 1 h at RT.…”

Section: Methodsmentioning

confidence: 99%

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The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer

Dyshlovoy

Menchinskaya

Venz

et al. 2016

Intl Journal of Cancer

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Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), outcome of patients remains poor due to the development of drug resistance. Thus, new drugs are urgently needed. We investigated efficacy, toxicity and mechanism of action of marine triterpene glycoside frondoside A (FrA) using CRPC cell lines in vitro and in vivo. FrA revealed high efficacy in human prostate cancer cells, while non-malignant cells were less sensitive. Remarkably, proliferation and colony formation of cells resistant to enzalutamide and abiraterone (due to the androgen receptor splice variant AR-V7) were also significantly inhibited by FrA. The marine compound caused cell type specific cell cycle arrest and induction of caspase-dependent or -independent apoptosis. Up-regulation or induction of several pro-apoptotic proteins (Bax, Bad, PTEN), cleavage of PARP and caspase-3 and down-regulation of anti-apoptotic proteins (survivin and Bcl-2) were detected in treated cells. Global proteome analysis revealed regulation of proteins involved in formation of metastases, tumor cell invasion, and apoptosis, like keratin 81, CrkII, IL-1b and cathepsin B. Inhibition of pro-survival autophagy was observed following FrA exposure. In vivo, FrA inhibited tumor growth of PC-3 and DU145 cells with a notable reduction of lung metastasis, as well as circulating tumor cells in the peripheral blood. Increased lymphocyte counts of treated animals might indicate an immune

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer

Dyshlovoy

Menchinskaya

Venz

et al. 2016

Intl Journal of Cancer

Self Cite

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“…40 However, Dyshlovoy et al reported that monanchocidin A ( 24 ) displayed up to 4-fold higher potency against several cancer cell lines than non-malignant cell lines. 47 Monanchocidin A ( 24 ) was also equally active in cisplatin-sensitive and -resistant germ cell tumor (GCT) cell lines. Strong synergistic effects of combined treatment of monanchocidin A ( 24 ) and cisplatin were observed as well 47 …”

Section: Toxicity and General Sar Picturementioning

confidence: 99%

“…47 Monanchocidin A ( 24 ) was also equally active in cisplatin-sensitive and -resistant germ cell tumor (GCT) cell lines. Strong synergistic effects of combined treatment of monanchocidin A ( 24 ) and cisplatin were observed as well 47 …”

Section: Toxicity and General Sar Picturementioning

confidence: 99%

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Structure, synthesis and biological properties of the pentacyclic guanidinium alkaloids

Shi

Moazami

Pierce

2017

Bioorganic & Medicinal Chemistry

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The pentacyclic guanidinium alkaloids (PGAs) are a family of marine natural products that possess a poly-cyclic guanidine-containing core and a long alkyl chain tethered spermidine-derived tail that is rarely observed in other natural products. These natural products exhibit potent activities on a wide range of organisms and therefore have attracted the attention of many synthetic chemists; however, the structure-activity relationships and mechanisms of action of PGAs remain largely elusive. Herein we summarize the structure, synthesis, toxicity and mechanisms of action of PGAs and highlight their potential as chemical probes and/or therapeutic leads.

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Caspase‐driven cancer therapies: Navigating the bridge between lab discoveries and clinical applications

Allani,

Akhilesh,

Tiwari

2024

Cell Biochemistry & Function

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Apoptosis is the cell's natural intrinsic regulatory mechanism of normal cells for programmed cell death, which plays an important role in cancer as a classical mechanism of tumor cell death causing minimal inflammation without causing damage to other cells in the vicinity. Induction of apoptosis by activation of caspases is one of the primary targets for cancer treatment. Over the years, a diverse range of natural, synthetic, and semisynthetic compounds and their derivatives have been investigated for their caspase‐mediated apoptosis‐induced anticancer activities. The review aims to compile the preclinical evidence and highlight the critical mechanistic pathways related to caspase‐induced cell apoptosis in cancer treatment. The focus is placed on the key components of the mechanisms, including their chemical nature, and specific attention is given to phytochemicals derived from natural sources and synthetic and semisynthetic compounds. 180+ compounds from the past two decades with potential as anticancer agents are discussed in this review article. By summarizing the current knowledge and advancements in this field, this review provides a comprehensive overview of potential therapeutic strategies targeting apoptosis in cancer cells. The findings presented herein contribute to the ongoing efforts to combat cancer and stimulate further research into the development of effective and targeted anticancer therapies.

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Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization

Cited by 63 publications

References 50 publications

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer

Structure, synthesis and biological properties of the pentacyclic guanidinium alkaloids

Caspase‐driven cancer therapies: Navigating the bridge between lab discoveries and clinical applications

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