| Full text | |
| Author(s): |
Takayasu, Bianca S.
[1, 2]
;
Martins, Igor R.
[3]
;
Garnique, Anali M. B.
[1]
;
Miyamoto, Sayuri
[4]
;
Machado-Santelli, Glaucia M.
[1]
;
Uemi, Miriam
[3]
;
Onuki, Janice
[2]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil
[2] Butantan Inst, Lab Dev & Innovat, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Chem, Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Archives of Biochemistry and Biophysics; v. 696, DEC 15 2020. |
| Web of Science Citations: | 1 |
| Abstract | |
beta-Sitosterol (beta Sito) is the most abundant phytosterol found in vegetable oils, grains such as wheat, beans, and corn, and in many phytosterol-enriched foods. It is prone to oxidation by reactive oxygen species, such as ozone, leading to the formation of oxyphytosterols. A better understanding regarding the biological effects and mechanism of action of oxyphytosterols is required since the beneficial and adverse side effects of these compounds on human health remain highly controversial. In this work, we investigated the biological effects of beta-Secosterol (beta Sec), a new oxyphytosterol generated by the reaction of beta Sito with ozone. Treatment of HepG2 cells with beta Sito or beta Sec (0.1-100 mu M) for 24, 48, and 72 h induced a dose-dependent reduction of cell viability in the MTT assay, with beta Sec showing higher efficacy than beta Sito. However, beta Sec presented a lower potency than beta Sito, showing IC50 = 37.32 mu M, higher than beta Sito (IC50 = 0.23 mu M) at 48 h. Cell cycle analyses by flow cytometry showed a slight decrease of G0/G1 phase with beta Sito 0.5 mu M, but a significant cell cycle arrest at the G0/G1 phase in the treatment for 48 h with beta Sec 20 mu M (62.69 +/- 2.15%, p < 0.05) and beta Sec 40 mu M (66.96 +/- 5.39%, p < 0.0001) when compared to control (56.97 +/- 2.60%). No suggestion of apoptosis was indicated by flow cytometry data. Also, beta Sec (20 and 40 mu M) reduced the mitotic index. In the laser scanning confocal microscopy analysis no alterations in cell morphology were observed with beta Sito (0.5 mu M). Nevertheless, round-shaped cells, abnormal nuclear morphology with shrinkage, and formation of microtubules clusters were observed in the treatment with beta Sec, indicating a disruption in the microtubules network organization. N-acetyl-L-cysteine was not able to inhibit any of these cellular effects, indicating a lack of involvement of oxidative stress in the mechanism of action of beta Sec. Although not further investigated in this study, it was discussed the hypothesis that covalent adduct formation with lysine residues of proteins, could play an important role in the biological effects elicited by beta Sec. Elucidation of the primary cellular processes induced by beta Sec provides the essential knowledge to be aware of its potential adverse side effects or therapeutic use of this oxyphytosterol. (AU) | |
| FAPESP's process: | 14/14801-8 - Are oxysterols able to modify ubiquitin and inhibit the proteolytic pathway by blockage of the ubiquitin proteasome system? |
| Grantee: | Miriam Uemi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds |
| Grantee: | Leticia Veras Costa Lotufo |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/19506-8 - 7th International Conference on Food Factors (ICoFF2019) & the 12th International Conference and Exhibition on Nutraceuticals and Functional Foods (ISNFF2019) |
| Grantee: | Janice Onuki |
| Support Opportunities: | Research Grants - Meeting - Abroad |