TY - JOUR
T1 - Combined effects of eicosapentaenoic acid and adipocyte renin–angiotensin system inhibition on breast cancer cell inflammation and migration
AU - Rasha, Fahmida
AU - Kahathuduwa, Chanaka
AU - Ramalingam, Latha
AU - Hernandez, Arelys
AU - Moussa, Hanna
AU - Moustaid-Moussa, Naima
N1 - Funding Information:
Funding: This work was supported by the Texas Tech University (TTU) Transdisciplinary Research Academy (N.M.-M.), TTU startup funds (N.M.-M.), and the Obesity Research Institute. Internal funds are used to cover the costs to publish in open access.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/1
Y1 - 2020/1
N2 - Obesity is a major risk factor for breast cancer (BC). Obesity-related metabolic alterations such as inflammation and overactivation of the adipose renin–angiotensin system (RAS) may contribute to the progression of BC. Clinically used antihypertensive drugs such as angiotensin-converting enzyme inhibitors (ACE-I) and dietary bioactive components such as eicosapentaenoic acid (EPA) are known for their anti-inflammatory and adipose RAS blocking properties. However, whether EPA enhances the protective effects of ACE-I in lessening adipocyte inflammation on BC cells has not been studied. We hypothesized that combined EPA and ACE-I would attenuate BC cell inflammation and migration possibly via adipose RAS inhibition. To test our hypothesis, we examined the (i) direct effects of an ACE-I (captopril (CAP)) or EPA, individually and combined, on MCF-7 and MDA-MB-231 human BC cells, and the (ii) effects of conditioned medium (CM) from human adipocytes pretreated with the abovementioned agents on BC cells. We demonstrated that CM from adipocytes pretreated with EPA with or without captopril (but not direct treatments of BC cells) significantly reduced proinflammatory cytokines expression in both BC cell lines. Additionally, cell migration was reduced in MDA-MB-231 cells in response to both direct and CM-mediated CAP and/or EPA treatments. In summary, our study provides a significant insight into added benefits of combining anti-inflammatory EPA and antihypertensive ACE-I to attenuate the effects of adipocytes on breast cancer cell migration and inflammation.
AB - Obesity is a major risk factor for breast cancer (BC). Obesity-related metabolic alterations such as inflammation and overactivation of the adipose renin–angiotensin system (RAS) may contribute to the progression of BC. Clinically used antihypertensive drugs such as angiotensin-converting enzyme inhibitors (ACE-I) and dietary bioactive components such as eicosapentaenoic acid (EPA) are known for their anti-inflammatory and adipose RAS blocking properties. However, whether EPA enhances the protective effects of ACE-I in lessening adipocyte inflammation on BC cells has not been studied. We hypothesized that combined EPA and ACE-I would attenuate BC cell inflammation and migration possibly via adipose RAS inhibition. To test our hypothesis, we examined the (i) direct effects of an ACE-I (captopril (CAP)) or EPA, individually and combined, on MCF-7 and MDA-MB-231 human BC cells, and the (ii) effects of conditioned medium (CM) from human adipocytes pretreated with the abovementioned agents on BC cells. We demonstrated that CM from adipocytes pretreated with EPA with or without captopril (but not direct treatments of BC cells) significantly reduced proinflammatory cytokines expression in both BC cell lines. Additionally, cell migration was reduced in MDA-MB-231 cells in response to both direct and CM-mediated CAP and/or EPA treatments. In summary, our study provides a significant insight into added benefits of combining anti-inflammatory EPA and antihypertensive ACE-I to attenuate the effects of adipocytes on breast cancer cell migration and inflammation.
KW - Adipocyte inflammation
KW - Breast cancer
KW - Eicosapentaenoic acid
KW - Obesity
KW - Renin–angiotensin system
UR - http://www.scopus.com/inward/record.url?scp=85079163977&partnerID=8YFLogxK
U2 - 10.3390/cancers12010220
DO - 10.3390/cancers12010220
M3 - Article
AN - SCOPUS:85079163977
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 1
M1 - 220
ER -