Distinct anti-proliferative effects of herbal melanin on human acute monocytic leukemia THP-1 cells and embryonic kidney
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(2020) 20:154
RESEARCH ARTICLE
BMC Complementary Medicine and Therapies
Open Access
Distinct anti-proliferative effects of herbal melanin on human acute monocytic leukemia THP-1 cells and embryonic kidney HEK293 cells Adila El-Obeid1,2,3,4†, Hala Alajmi2,4†, Mashael Harbi1,4, Wesam Bin Yahya1,4, Hamad Al-Eidi1,4, Monira Alaujan1,4, Adil Haseeb6, Thadeo Trivilegio7,4, Alshaimaa Alhallaj7,4, Saleh Alghamdi1,4, Abdul-Wali Ajlouni5 and Sabine Matou-Nasri1,4*
Abstract Background: Herbal melanin (HM) is a dark pigment extracted from the seed coat of Nigella sativa L. and known to exert biological effects via toll-like receptor 4 (TLR4). Recently, TLR4 was described as involved in natural programmed cell death (apoptosis). Tumor and embryonic cells are used as in vitro cellular models for drug and anti-cancer agent screening. To date, no cytotoxic studies have been reported of HM in TLR4positive acute monocytic leukemia THP-1 cells compared to TLR4-negative human embryonic kidney HEK293 cells. Methods: We studied the anti-proliferative effects of several HM concentrations on THP-1 and HEK293 cells by evaluating cell viability using the CellTiter-Glo® luminescent assay, assessing the TLR4 expression level, determining the apoptotic status, and analyzing the cell cycle distribution using flow cytometry. Apoptotic pathways were investigated using mitochondrial transition pore opening, caspase activity assays and immunoblot technology. Results: Low HM concentrations did not affect THP-1 cell viability, but high HM concentrations (62.5–500 μg/ mL) did decrease THP-1 cell viability and induced G0/G1 phase cell cycle arrest. Only at the highest concentration (500 μg/mL), HM slightly increased the TLR4 expression on the THP-1 cell surface, concomitantly upregulated TLR4 whole protein and gene expression, and induced apoptosis in THP-1 cells via activation of the extrinsic and intrinsic pathways. No change of apoptotic status was noticed in TLR4-negative HEK293 cells, although HM decreased HEK293 cell viability and induced cell growth arrest in the G2 phase. (Continued on next page)
* Correspondence: [email protected] † Adila El-Obeid and Hala Alajmi contributed equally to this work. 1 Cell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, P.O. Box 22490, Riyadh 11426, Saudi Arabia 4 King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons lice
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