Tumoricidal properties of thymoquinone on human colorectal adenocarcinoma cells via the modulation of autophagy.

Autor:	Moulana MS; Department of Persian Medicine, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran., Haiaty S; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Bazmani A; Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Shabkhizan R; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Moslehian MS; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Sadeghsoltani F; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences, Tabriz, Iran., Mostafazadeh M; Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences, Tabriz, Iran., Asadi MR; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Talebi M; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Jafari Z; Department of Persian Medicine, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran., Morovati MR; Department of Persian Medicine, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran., Farzaei MH; Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. mh.farzaei@gmail.com.; Department of Traditional Pharmacy, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. mh.farzaei@gmail.com., Rahbarghazi R; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. rezarahbardvm@gmail.com.; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. rezarahbardvm@gmail.com.
Jazyk:	angličtina
Zdroj:	BMC complementary medicine and therapies [BMC Complement Med Ther] 2024 Mar 26; Vol. 24 (1), pp. 132. Date of Electronic Publication: 2024 Mar 26.
DOI:	10.1186/s12906-024-04432-2
Abstrakt:	Colorectal cancer (CRC) is deadly anaplastic changes in the gastrointestinal tract with high-rate mortality. In recent years, the application of phytocompounds has been extended along with different therapeutic protocols. Here, we monitored the effects of Thymoquinone (TQ) on autophagy via mitochondrial function after modulation of the Wnt/β-catenin signaling pathway.Human colorectal adenocarcinoma HT-29 cells were treated with TQ (60 µM) and 15 µM Wnt3a inhibitor (LGK974) for 48 h. The survival rate was evaluated using an MTT assay. The expression of Wnt-related factors (c-Myc, and Axin), angiogenesis (VE-Cadherin), and mitophagy-related factors (PINK1, OPTN) was assessed using real-time PCR assay. Protein levels of autophagy factors (Beclin-1, LC3, and P62) were monitored using western blotting. Using flow cytometry analysis, the intracellular accumulation of Rhodamine 123 was evaluated. The migration properties were analyzed using a scratch wound healing assay.Data indicated that TQ can reduce the viability of HT-29 cells compared to the control cells (p < 0.05). The expression of VE-Cadherin was inhibited while the expression of PINK1 was induced in treated cells (p < 0.05). Both LGK974 and TQ-treated cells exhibited activation of autophagy flux (Beclin-1↑, LC3II/I↑, and p62↓) compared to the control group (p < 0.05). TQ can increase intracellular accumulation of Rhodamine 123, indicating the inhibition of efflux mechanisms in cancer cells. Along with these changes, the migration of cells was also reduced (p < 0.05).TQ is a potential phytocompound to alter the dynamic growth of human colorectal HT-29 cells via the modulation of autophagy, and mitophagy-related mechanisms. (© 2024. The Author(s).)
Databáze:	MEDLINE
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