Osthole interacts with an ER-mitochondria axis and facilitates tumor suppression in ovarian cancer

doi:10.1002/jcp.29913

. 2021 Feb;236(2):1025-1042.

doi: 10.1002/jcp.29913. Epub 2020 Jul 22.

Osthole interacts with an ER-mitochondria axis and facilitates tumor suppression in ovarian cancer

Hyocheol Bae¹, Jin-Young Lee², Jisoo Song³, Gwonhwa Song¹, Whasun Lim³

Affiliations

¹ Department of Biotechnology, Korea University, Seoul, Republic of Korea.
² Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
³ Department of Food and Nutrition, Kookmin University, Seoul, Republic of Korea.

PMID: 32697363
DOI: 10.1002/jcp.29913

Osthole interacts with an ER-mitochondria axis and facilitates tumor suppression in ovarian cancer

Hyocheol Bae et al. J Cell Physiol. 2021 Feb.

. 2021 Feb;236(2):1025-1042.

doi: 10.1002/jcp.29913. Epub 2020 Jul 22.

Authors

Hyocheol Bae¹, Jin-Young Lee², Jisoo Song³, Gwonhwa Song¹, Whasun Lim³

Affiliations

¹ Department of Biotechnology, Korea University, Seoul, Republic of Korea.
² Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.
³ Department of Food and Nutrition, Kookmin University, Seoul, Republic of Korea.

PMID: 32697363
DOI: 10.1002/jcp.29913

Abstract

Osthole is a natural coumarin found in a variety of plants and has been reported to have diverse biological functions, including antimicrobial, antiviral, immunomodulatory, and anticancer effects. Here, we investigated the natural derivative osthole as a promising anticancer compound against ovarian cancer and evaluated its ability to suppress and abrogate tumor progression. In addition, we found the endoplasmic reticulum-mitochondrial axis-mediated anticancer mechanisms of osthole against ES2 and OV90 ovarian cancer cells and demonstrated its calcium-dependent pharmacological potential. Mechanistically, osthole was found to target the phosphatidylinositol 3-kinase/mitogen-activated protein kinase signaling pathway to facilitate tumor suppression in ovarian cancer. Furthermore, we identified the effects of osthole in a three-dimensional tumor-formation model using the zebrafish xenograft assay, providing convincing evidence of the pharmacological effects of osthole within the anchorage-independent tumor microenvironment. These findings suggest that osthole has strong potential as a pharmacological agent for targeting ovarian cancer.

Keywords: apoptosis; calcium homeostasis; osthole; ovarian cancer; zebrafish.

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References

REFERENCES

1. Azimi, I., Roberts-Thomson, S. J., & Monteith, G. R. (2014). Calcium influx pathways in breast cancer: Opportunities for pharmacological intervention. British Journal of Pharmacology, 171(4), 945-960. https://doi.org/10.1111/bph.12486
1. Bae, H., Lee, J. Y., Song, G., & Lim, W. (2020). Function of CCL5 in maternal-fetal interface of pig during early pregnancy. Developmental and Comparative Immunology, 103, 103503. https://doi.org/10.1016/j.dci.2019.103503
1. Bae, H., Lim, W., Bazer, F. W., Whang, K. Y., & Song, G. (2019). Mitigation of ER-stress and inflammation by chemokine (C-C motif) ligand 21 during early pregnancy. Developmental and Comparative Immunology, 94, 73-84. https://doi.org/10.1016/j.dci.2019.01.016
1. du Bois, A., Reuss, A., Pujade-Lauraine, E., Harter, P., Ray-Coquard, I., & Pfisterer, J. (2009). Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer, 115(6), 1234-1244. https://doi.org/10.1002/cncr.24149
1. Bosanac, I., Alattia, J. R., Mal, T. K., Chan, J., Talarico, S., Tong, F. K., … Ikura, M. (2002). Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature, 420(6916), 696-700. https://doi.org/10.1038/nature01268

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[1] Azimi, I., Roberts-Thomson, S. J., & Monteith, G. R. (2014). Calcium influx pathways in breast cancer: Opportunities for pharmacological intervention. British Journal of Pharmacology, 171(4), 945-960. https://doi.org/10.1111/bph.12486

[2] Azimi, I., Roberts-Thomson, S. J., & Monteith, G. R. (2014). Calcium influx pathways in breast cancer: Opportunities for pharmacological intervention. British Journal of Pharmacology, 171(4), 945-960. https://doi.org/10.1111/bph.12486

[3] Bae, H., Lee, J. Y., Song, G., & Lim, W. (2020). Function of CCL5 in maternal-fetal interface of pig during early pregnancy. Developmental and Comparative Immunology, 103, 103503. https://doi.org/10.1016/j.dci.2019.103503

[4] Bae, H., Lee, J. Y., Song, G., & Lim, W. (2020). Function of CCL5 in maternal-fetal interface of pig during early pregnancy. Developmental and Comparative Immunology, 103, 103503. https://doi.org/10.1016/j.dci.2019.103503

[5] Bae, H., Lim, W., Bazer, F. W., Whang, K. Y., & Song, G. (2019). Mitigation of ER-stress and inflammation by chemokine (C-C motif) ligand 21 during early pregnancy. Developmental and Comparative Immunology, 94, 73-84. https://doi.org/10.1016/j.dci.2019.01.016

[6] Bae, H., Lim, W., Bazer, F. W., Whang, K. Y., & Song, G. (2019). Mitigation of ER-stress and inflammation by chemokine (C-C motif) ligand 21 during early pregnancy. Developmental and Comparative Immunology, 94, 73-84. https://doi.org/10.1016/j.dci.2019.01.016

[7] du Bois, A., Reuss, A., Pujade-Lauraine, E., Harter, P., Ray-Coquard, I., & Pfisterer, J. (2009). Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer, 115(6), 1234-1244. https://doi.org/10.1002/cncr.24149

[8] du Bois, A., Reuss, A., Pujade-Lauraine, E., Harter, P., Ray-Coquard, I., & Pfisterer, J. (2009). Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer, 115(6), 1234-1244. https://doi.org/10.1002/cncr.24149

[9] Bosanac, I., Alattia, J. R., Mal, T. K., Chan, J., Talarico, S., Tong, F. K., … Ikura, M. (2002). Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature, 420(6916), 696-700. https://doi.org/10.1038/nature01268

[10] Bosanac, I., Alattia, J. R., Mal, T. K., Chan, J., Talarico, S., Tong, F. K., … Ikura, M. (2002). Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature, 420(6916), 696-700. https://doi.org/10.1038/nature01268

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Osthole interacts with an ER-mitochondria axis and facilitates tumor suppression in ovarian cancer

Affiliations

Osthole interacts with an ER-mitochondria axis and facilitates tumor suppression in ovarian cancer

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