Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

doi:10.1016/j.bbrc.2016.04.028

Cited by 23 publications

(20 citation statements)

References 31 publications

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“…ETC complex I, constitutes the entry point of electrons and is an essential site for ROS generation (33). Caulerpin has been reported to reduce respiratory complex II activity and to exhibit cytotoxicity to human dermal fibroblasts (14). In this study, caulerpin considerably reduced oxygen consumption rate and ATP level in both SW480 and LOVO cells, accompanied by an elevation in ROS.…”

Section: Discussionmentioning

confidence: 56%

“…In this study, caulerpin considerably reduced oxygen consumption rate and ATP level in both SW480 and LOVO cells, accompanied by an elevation in ROS. Mitochondria isolated from rat liver have been selected as a system in which mechanisms of bioenergetics are not altered (14). Therefore, liver mitochondrial and LOVO cells were used to explore the complex interactions between caulerpin and the organelle.…”

Section: Discussionmentioning

confidence: 99%

“…algal pigment, was first mentioned by Liu et al (13), who suggested that mitochondrial respiration can be intervened by caulerpin via suppressing ETC complex I of breast cancer cells in hypoxia. Recently, the study group of Ferramosca et al found that caulerpin selectively repressed the activity of complex II in rat liver mitochondria (14). The observations that caulerpin suppresses HIF-1 activation and displays cytotoxicity to human dermal fibroblasts support further exploration into the anticancer mechanism of caulerpin.…”

Section: Metabolic Reprogramming and Ampkα1 Pathway Activation By Caumentioning

confidence: 94%

“…Previous findings illustrated that caulerpin impaired mitochondrial ETC in cisplatin-resistant C13 cells and human breast cancer T47D cells (13,14), but its effects on oxygen consumption have not been fully addressed. Additionally, whether the emergence of an energy stress correlates with the anticancer activity of caulerpin in colorectal cells needs to be explored.…”

Section: Caulerpin Inhibits Oxphos and Disturbs Mitochondrial Functiomentioning

confidence: 99%

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Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

Zhang

Dong

et al. 2016

International Journal of Oncology

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Caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea is known to induce mitochondrial dysfunctions. In this study, the anticancer property of caulerpin was assessed in a panel of colorectal cancer cell lines. We demonstrated that caulerpin inhibited oxidative phosphorylation (OXPHOS) and facilitated an early intervention of the mitochondrial function, via inhibiting mitochondrial complex I, accompanied by the dissipation of mitochondrial membrane potential and a surge of reactive oxygen species (ROS) generation. Moreover, in response to the increment in AMP/ATP ratio, the energy sensor AMP-activated protein kinase (AMPK) was activated by caulerpin treatment in a calcium/calmodulin-dependent protein kinase 2 (CaMKK2)‑dependent manner. Distinguished effect on glycolysis was observed at different time-points after caulerpin treatment. Glycolysis was enhanced after a short time treatment with caulerpin, associated with upregulation of glucose transporter 1 (GLUT1), hexokinase II (HKII) and 6-phosphofructo-2-kinase (PFKFB3) protein expressions. However, long-term activation of AMPK by caulerpin damaged the glycolysis and glucose metabolism in colorectal cells, finally causing cell death. The persistent effect of caulerpin was mediated by AMPKα1, rather than AMPKα2, to abolish cell viability through hindering mTORC1-4E-BP1 axis. Moreover, caulerpin synergized with the glycolytic inhibitor 3BP in inhibiting cellular proliferation both in vitro and in vivo. Our findings on the previously uncharacterized anticancer effects of caulerpin may provide potential therapeutic approaches targeting the colorectal carcinoma metabolism.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Metabolic Reprogramming and Ampkα1 Pathway Activation By Caumentioning

confidence: 94%

Section: Caulerpin Inhibits Oxphos and Disturbs Mitochondrial Functiomentioning

confidence: 99%

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Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

Zhang

Dong

et al. 2016

International Journal of Oncology

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“…Caulerpin 53 overpowers the mitochondrial respiratory at complex II and increases ROS production in cisplatin-resistant C13 ovarian cancer cells, while it has no effect on the complexes I, III and IV [ 169 ], suggesting that some derivatives could be good candidates for the treatment of cisplatin-resistant cancer, once ovarian cancer cisplatin resistant cells are characterized by reduced oxygen consumption and increased dependence on glucose [ 170 ].…”

Section: Secondary Metabolites From Seaweeds With In Vitro Cytotoxmentioning

confidence: 99%

Seaweed Secondary Metabolites In Vitro and In Vivo Anticancer Activity

2018

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Isolation, finding or discovery of novel anticancer agents is very important for cancer treatment, and seaweeds are one of the largest producers of chemically active metabolites with valuable cytotoxic properties, and therefore can be used as new chemotherapeutic agents or source of inspiration to develop new ones. Identification of the more potent and selective anticancer components isolated from brown, green and red seaweeds, as well as studies of their mode of action is very attractive and constitute a small but relevant progress for pharmacological applications. Several researchers have carried out in vitro and in vivo studies in various cell lines and have disclosed the active metabolites among the terpenoids, including carotenoids, polyphenols and alkaloids that can be found in seaweeds. In this review the type of metabolites and their cytotoxic or antiproliferative effects will be discussed additionally their mode of action, structure-activity relationship and selectivity will also be revealed. The diterpene dictyolactone, the sterol cholest-5-en-3β,7α-diol and the halogenated monoterpene halomon are among the reported compounds, the ones that present sub-micromolar cytotoxicity. Additionally, one dimeric sesquiterpene of the cyclolaurane-type, three bromophenols and one halogenated monoterpene should be emphasized because they exhibit half maximal inhibitory concentration (IC50) values between 1–5 µM against several cell lines.

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Natural Inhibitors of Mitochondrial Respiratory Chain: Therapeutic and Toxicological Implications

Peláez

Pedro

Tormo

2017

Natural Products Targeting Clinically Relevant Enzymes

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Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

Cited by 23 publications

References 31 publications

Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

Metabolic reprogramming and AMPKα1 pathway activation by caulerpin in colorectal cancer cells

Seaweed Secondary Metabolites In Vitro and In Vivo Anticancer Activity

Natural Inhibitors of Mitochondrial Respiratory Chain: Therapeutic and Toxicological Implications

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