Physciosporin suppresses mitochondrial respiration, aerobic glycolysis, and tumorigenesis in breast cancer

Taş, İsa; Varlı, Mücahit; Son, Yeseon; Han, Jing; Kwak, Dahye; Yang, Yi; Zhou, Rui; Gamage, Chathurika D. B.; Pulat, Sultan; Park, So‐Yeon; Yu, Young Hyun; Moon, Kyung‐Sub; Lee, Kyung‐Hwa; Ha, Hyung‐Ho; Hur, Jae‐Seoun; Kim, Hangun

doi:10.1016/j.phymed.2021.153674

Cited by 17 publications

(14 citation statements)

References 56 publications

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“…To investigate the anti-proliferative potential of the ELF-derived compounds in vitro , a clonogenic assay was performed in H1975 cells. Cancer cell proliferation and tumor growth are the defining features of cancer progression ( Taş et al, 2021 ). The proliferative capacity of the H1975 cells were suppressed significantly by radianspenes C and D, and dahliane D, in a dose-dependent manner ( Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

An acetonic extract and secondary metabolites from the endolichenic fungus Nemania sp. EL006872 exhibit immune checkpoint inhibitory activity in lung cancer cell

et al. 2022

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Background: Endolichenic fungi (ELF), which live the inside the lichen thallus, contain many secondary metabolites that show various biological activities. Recent studies show that lichen and ELF secondary metabolites have antioxidant, antibacterial, antifungal, cytotoxic, and anticancer activities.Purpose: Here, the effects of an ELF extract and its bioactive compounds were investigated on the H1975 cell line focusing on immune checkpoint marker inhibition.Methods: An ELF was isolated from the host lichen Bryoria fuscescens (Gyelnik) Brodo and D. Hawksw and identified the species as Nemania sp. EL006872. The fungus was cultured on agar medium and acetonic extracts were obtained. Secondary metabolites radianspenes C and D, and dahliane D, were isolated from the crude extract. The biological effects of both the crude extract and the isolated secondary metabolites were evaluated in cell viability, qRT-PCR assays, flow cytometry analysis and western blotting.Results: The cell viability assay revealed that extracts from Nemania sp. EL006872 and the isolated secondary compounds had low cytotoxicity. The crude extract, radianspenes C and D, and dahliane D, suppressed expression of mRNA encoding PD-L1 and aromatic hydrocarbon receptor (AhR), and surface expression of PD-L1 protein by cells exposed to benzo[a] pyrene. Radianspenes C and D, and dahliane D, reduced expression of AhR, PD-L1, ICOSL, and GITRL proteins by H1975 lung cancer cells, as well as exerting anti-proliferative effects.Conclusion: Radianspenes C and D, and dahliane D, bioactive compounds isolated from Nemania sp. EL006872 ELF, have the potential for use as immunotherapy and immunoncology treatments.

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Section: Resultsmentioning

confidence: 99%

An acetonic extract and secondary metabolites from the endolichenic fungus Nemania sp. EL006872 exhibit immune checkpoint inhibitory activity in lung cancer cell

et al. 2022

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“…Combinational drug therapy is a viable and effective strategy for cancer treatment. Apart from the compounds mentioned above, other small-molecule compounds that induce apoptosis of TNBC cells by regulating Bcl-2 family proteins are also summarized in Table 1 [ 62 – 70 ].…”

Section: Targeting Apoptotic Pathways With Small-molecule Compounds I...mentioning

confidence: 99%

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

et al. 2022

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Triple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies. Graphical abstract

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“…Physciosporin : Physciosporin is one of the potent anticancer lichen compounds shown to suppress colorectal cancer cell proliferation, motility, and tumorigenesis (Taş et al, 2019; Yang et al, 2015). Taş et al (2021) have investigated the anticancer effect of physciosporin on human breast cancer (MCF‐7 and MDA‐MB‐231) cells. Physciosporin triggered apoptosis in a cancer cell by regulating the B‐cell lymphoma‐2 (Bcl‐2) family proteins and the activity of the caspase pathway.…”

Section: Natural Product Inhibitors Of Pkm2mentioning

confidence: 99%

Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics

El‐Far

Jaouni

et al. 2022

Phytotherapy Research

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Glycolysis is the primary source of energy for cancer growth and metastasis. The shift in metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis is called the Warburg effect. Cancer progression due to aerobic glycolysis is often associated with the activation of oncogenes or the loss of tumor suppressors. Therefore, inhibition of glycolysis is one of the effective strategies in cancer control. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in breast, prostate, lung, colorectal, and liver cancers. Here, we discuss published studies regarding PKM2 inhibitors from natural products that are promising drug candidates for cancer therapy. We have highlighted the potential of natural PKM2 inhibitors for various cancer types. Moreover, we encourage researchers to evaluate the combinational effects between natural and synthetic PKM2 inhibitors. Also, further high‐quality studies are needed to firmly establish the clinical efficacy of natural products.

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Physciosporin suppresses mitochondrial respiration, aerobic glycolysis, and tumorigenesis in breast cancer

Cited by 17 publications

References 56 publications

An acetonic extract and secondary metabolites from the endolichenic fungus Nemania sp. EL006872 exhibit immune checkpoint inhibitory activity in lung cancer cell

An acetonic extract and secondary metabolites from the endolichenic fungus Nemania sp. EL006872 exhibit immune checkpoint inhibitory activity in lung cancer cell

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics

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