Krill oil ameliorates benign prostatic hyperplasia by regulating G<sub>1</sub>-phase cell cycle arrest and altering signaling pathways and benign prostatic hyperplasia-associated markers

Hoon Kim; Jongyeob Kim; Byungdoo Hwang; SangYong Park; Ji-Yeon Shin; EunByeol Go; Jae Sil Kim; Youngjin Roh; SoonChul Myung; Seok-Joong Yun; YungHyun Choi; Wun-Jae Kim; Sung-Kwon Moon

doi:10.26599/FSHW.2023.9250017

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Open Access

Krill oil ameliorates benign prostatic hyperplasia by regulating G₁-phase cell cycle arrest and altering signaling pathways and benign prostatic hyperplasia-associated markers

Hoon Kim^{^a}, Jongyeob Kim^{^a}, Byungdoo Hwang^{^a}, SangYong Park^{^b}, Ji-Yeon Shin^{^b}, EunByeol Go^{^b}, Jae Sil Kim^{^b}, Youngjin Roh^{^a}, SoonChul Myung^{^c}, Seok-Joong Yun^{^d}, YungHyun Choi^{^e}, Wun-Jae Kim^{^f}, Sung-Kwon Moon^{^a}()

Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Republic of Korea

SD Biotechnologies, Seoul 07793, Republic of Korea

Department of Urology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea

Department of Urology, Chungbuk National University, Chungbuk 361-763, Republic of Korea

Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 47340, Republic of Korea

Institute of Urotech, Cheongju, Chungcheongbuk-do 361-763, Republic of Korea

Peer review under responsibility of Tsinghua University Press.

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Highlights

• Krill oil (KO) inhibits proliferation of normal prostatic cells

• KO induces G₁-phase cell cycle arrest via regulation of CDKs, cyclins, and CDKIs

• KO affects signaling pathway and proliferation-mediated NF-κB binding activity

• Oral administration of KO improves BPH in a rat model

• KO modulates expression of BPH-associated markers in vitro and in vivo

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Abstract

Krill oil (KO) exhibits various biological activities, such as anti-inflammatory and antitumor effects. However, the inhibitory effects of benign prostatic hyperplasia (BPH) in vitro and in vivo have not yet been studied. This study investigated the anti-BPH effects of KO extracted by an enzymatic hydrolysis method. KO treatment inhibited the proliferation of WMPY-1 and BPH-1 cells by induction of G₀/G₁ phase arrest through the modulation of positive and negative regulators in both prostate cell types. KO treatment stimulated phosphorylation of c-Jun N-terminal kinase (JNK) and p38 signaling. In addition, KO changed the expression of BPH-related markers (5α-reductase, androgen receptor, FGF, Bcl-2, and Bax) and the activity of the proliferation-mediated NF-κB binding motif. KO-induced levels of proliferation-mediated molecules of prostate cells were attenuated in the presence of siRNA-specific p-38 (si-p38) and JNK (si-JNK). Furthermore, the administration of KO alleviated prostate size and weight and the cell layer thickness of prostate glands in a testosterone enanthate-induced BPH rat model. KO treatment altered the level of dihydrotestosterone in serum and the expression levels of BPH-related markers in prostate tissues. Finally, KO-mediated inhibition of prostatic growth was validated by histological analysis. These results suggest that KO has an inhibitory effect on BPH in prostate cells in vitro and in vivo. Thus, KO might be a potential prophylactic or therapeutic agent for patients with BPH.

Keywords

Proliferation G₀/G₁-phase cell cycle NF-κB Dihydrotestosterone

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References

[1]

J. Sausville, M. Naslund. Benign prostatic hyperplasia and prostate cancer: an overview for primary care physicians, Int. J. Clin. Pract. 64 (2010) 1740-1745. http://doi.org/10.1111/j.1742-1241.2010.02534.x.

Krill oil ameliorates benign prostatic hyperplasia by regulating G1-phase cell cycle arrest and altering signaling pathways and benign prostatic hyperplasia-associated markers