Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro
Oxidative damage and inflammation are among the very significant aspects interrelated with cancer and other degenerative diseases. In this study, we investigated the biological activities of a 25 kDa protease (SH21) that was purified from <i>Bacillus siamensis</i>. SH21 exhibited very po...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/17/2190 |
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| author | Hasan Tarek Seung Sik Cho Md. Selim Hossain Jin Cheol Yoo |
| author_facet | Hasan Tarek Seung Sik Cho Md. Selim Hossain Jin Cheol Yoo |
| author_sort | Hasan Tarek |
| collection | DOAJ |
| description | Oxidative damage and inflammation are among the very significant aspects interrelated with cancer and other degenerative diseases. In this study, we investigated the biological activities of a 25 kDa protease (SH21) that was purified from <i>Bacillus siamensis</i>. SH21 exhibited very powerful antioxidant and reactive oxygen species (ROS) generation inhibition activity in a dose-dependent approach. The mRNA and protein levels of antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (GPx-1) were enhanced in the SH21-treated sample. SH21 also increased the transcriptional and translational activities of NF-E2-related factor 2 (Nrf2) with the subsequent development of detoxifying enzyme heme oxygenase-1 (HO-1). In addition, SH21 showed potential anti-inflammatory activity via inhibition of nitric oxide (NO) and proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. At concentrations of 60, 80, and 100 μg/mL, SH21 potentially suppressed nitric oxide synthase (iNOS) and cytokine gene expressions. Furthermore, SH21 significantly released lactate dehydrogenase (LDH) enzyme in cancer cell supernatant in a concentration-dependent manner and showed strong activity against three tested cancer cell lines, including HL-60, A549, and Hela. Our results suggest that SH21 has effective antioxidant, anti-inflammatory, and anticancer effects and could be an excellent therapeutic agent against inflammation-related diseases. |
| first_indexed | 2024-03-10T23:26:12Z |
| format | Article |
| id | doaj.art-e2a0a9ea4e834d208263d5dc49b82b3d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T23:26:12Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-e2a0a9ea4e834d208263d5dc49b82b3d2023-11-19T07:58:29ZengMDPI AGCells2073-44092023-09-011217219010.3390/cells12172190Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In VitroHasan Tarek0Seung Sik Cho1Md. Selim Hossain2Jin Cheol Yoo3Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju 61452, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Mokpo National University, Muan 58554, Republic of KoreaDepartment of Biomedical Sciences, Chosun University, Gwangju 61452, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Chosun University, Gwangju 61452, Republic of KoreaOxidative damage and inflammation are among the very significant aspects interrelated with cancer and other degenerative diseases. In this study, we investigated the biological activities of a 25 kDa protease (SH21) that was purified from <i>Bacillus siamensis</i>. SH21 exhibited very powerful antioxidant and reactive oxygen species (ROS) generation inhibition activity in a dose-dependent approach. The mRNA and protein levels of antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (GPx-1) were enhanced in the SH21-treated sample. SH21 also increased the transcriptional and translational activities of NF-E2-related factor 2 (Nrf2) with the subsequent development of detoxifying enzyme heme oxygenase-1 (HO-1). In addition, SH21 showed potential anti-inflammatory activity via inhibition of nitric oxide (NO) and proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. At concentrations of 60, 80, and 100 μg/mL, SH21 potentially suppressed nitric oxide synthase (iNOS) and cytokine gene expressions. Furthermore, SH21 significantly released lactate dehydrogenase (LDH) enzyme in cancer cell supernatant in a concentration-dependent manner and showed strong activity against three tested cancer cell lines, including HL-60, A549, and Hela. Our results suggest that SH21 has effective antioxidant, anti-inflammatory, and anticancer effects and could be an excellent therapeutic agent against inflammation-related diseases.https://www.mdpi.com/2073-4409/12/17/2190protease SH21oxidative damageantioxidantsanti-inflammatoryanticancer |
| spellingShingle | Hasan Tarek Seung Sik Cho Md. Selim Hossain Jin Cheol Yoo Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro Cells protease SH21 oxidative damage antioxidants anti-inflammatory anticancer |
| title | Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro |
| title_full | Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro |
| title_fullStr | Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro |
| title_full_unstemmed | Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro |
| title_short | Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro |
| title_sort | attenuation of oxidative damage via upregulating nrf2 ho 1 signaling pathway by protease sh21 with exerting anti inflammatory and anticancer properties in vitro |
| topic | protease SH21 oxidative damage antioxidants anti-inflammatory anticancer |
| url | https://www.mdpi.com/2073-4409/12/17/2190 |
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