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Mechanism of Action of Isotretinoin
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Isotretinoin and ATRA show similar effects on cell growth in primary human keratinocytes and HaCaT cultures tested with increasing proliferation at low cell densities. They are rather inactive at high ones in normal keratinocytes and exhibit an antiproliferative effect in HaCaT keratinocytes (168). Isotretinoin added to human pilosebaceous ducts in culture causes an additional significant reduction in the rate of [3H] thymidine uptake, pointing to reduced epithelial duct proliferation during isotretinoin treatment (169).
Biochemical Aspects of Nickel Hypersensitivity: Factors Determining Allergenic Action
Published in Jurij J. Hostýnek, Howard I. Maibach, Nickel and the Skin, 2019
Baldassarré Santucci, Emanuela Camera, Mauro Picardo
Recent studies have compared the effect of various sensitizing agents in cultured normal human keratinocytes and transformed human keratinocyte HaCaT cell lines and in conditions favoring either cell proliferation or differentiation. In the proliferative HaCaT cell line, following 24-h exposure, nickel produced a concentration-dependent up-regulation of ICAM-1 expression without reducing cell viability. In normal human keratinocytes, NiSO4 induced ICAM-1 expression to a significantly greater extent in proliferative cells than in differentiated cells. Interestingly, among the nickel-containing compounds tested, NiSO4, NiCI2, NiCitrate, and Ni(His)2 complex, the latter was the less effective in the up-regulation of ICAM-1 expression (Wagner et al., 1997).
New Models to Assess in Vitro Action of Retinoids
Published in Francis N. Marzulli, Howard I. Maibach, Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
HaCaT, a spontaneously transformed human keratinocyte cell line (Boukamp et al., 1988), was used to study the apoptotic potential of several retinoids. Apoptosis was followed by using TUNEL staining. Among all the tested retinoids, CD437, a RARγ selective agonist, was shown to be the most active compound. Figure 3 shows the TUNEL staining obtained after treatment for 24 hr with CD437 at 1 μM compared to mock treated cells. Induction of apoptosis is a rapid process since it is apparent after treatment for 24 hr. Apoptosis is also visible after treatment of HaCaT cells with a lower concentration of CD437 (0.3 μM) revealing the high potency of this compound. Since CD437 is a RARγ selective retinoid, it is tempting to conclude that this receptor subtype is mediating apoptosis in HaCaT keratinocytes.
B-Raf inhibitor vemurafenib counteracts sulfur mustard-induced epidermal impairment through MAPK/ERK signaling
Published in Drug and Chemical Toxicology, 2023
Zhiyong Xiao, Feng Liu, Junping Cheng, Ying Wang, Wenxia Zhou, Yongxiang Zhang
The therapeutic effect of dual therapy may be attributed to the blockade of the MEK inhibitor on the paradoxical activation of the MAP kinase pathway by Raf inhibitors (Roskoski 2018, 2019). Although Raf inhibitors sustain MEK/ERK phosphorylation inhibition in B-RafV600E A375 cells, these agents promote cell survival and increased phospho-MEK and phospho-ERK levels in WT Ras and RAS-mutated cancer cell lines without B-Raf mutations (Hatzivassiliou et al.2010). Consistent with these results, we found that vemurafenib protected HaCaT cells from SM-induced cell death and simultaneously enhanced phosphorylation of ERK1/2 (Figure 4). HaCaT is an immortal human keratinocyte line with mutated p53 and intact Ras or Raf (Lehman et al.1993). Thus, the apparent phosphorylation of ERK1/2 after vemurafenib treatment observed in our study might be a consequence of the activation of the EGFR/Ras pathway in the non-Raf mutant background.
Assessment of genotoxicity induced by subchronic exposure to graphene in HaCaT human skin cell line
Published in Nanotoxicology, 2023
Javier Frontiñan-Rubio, Sonia García-Carpintero, Viviana Jehová González, Ester Vázquez, Mario Durán-Prado
In this work, we established different HaCaT sublines for subchronic GBMs exposure. HaCaTs are a spontaneously immortalized, nontumorigenic human keratinocyte cell line used previously to study graphene-induced toxicity (Pelin et al. 2017, 2018; Frontiñán-Rubio et al. 2018, 2020). HaCaT cells are also suitable for long-term culture due to their chromosomal stability (Boukamp et al. 1988, 1997; Deyrieux and Wilson 2007). Four different GBMs, with different oxidation degrees and lateral dimensions (Figures 1 and 2) were used: two commercial GOs prepared from different starting materials (carbon nanofibers—GO 1and graphite—GO 2); and two FLGs (FLG 1 and FLG 2) manufactured in our laboratory (González-Domínguez et al. 2018; González et al. 2018). These GBMs had different lateral dimensions and sizes (Figures 1 and 2) (Pelin et al. 2017; Frontiñán-Rubio et al. 2018). Cells were treated once a week with two different sub-lethal doses of GBMs (0.5 and 5 µg/mL) (Pelin et al. 2017; Frontiñán-Rubio et al. 2018) for 14 days, 30 days, 3 months, and 6 months (Figure 1), generating a continuous exposure to the different GBMs intended to simulate the conditions that can arise from different applications or in the workplace.
Co-delivery of isotretinoin and clindamycin by phospholipid-based mixed micellar system confers synergistic effect for treatment of acne vulgaris
Published in Expert Opinion on Drug Delivery, 2021
Gajanand Sharma, Yukhti Yachha, Kanika Thakur, Akanksha Mahajan, Gurjeet Kaur, Bhupinder Singh, Kaisar Raza, OP Katare
Very few studies have reported the in vitro toxicity of topical retinoids like ITR on human skin cells. HaCat cells are the immortal human keratinocyte cells, which have been employed in many studies as standard for epidermal keratinocytes. Untreated HaCat cells served as the control. MTT assay is employed to measure the viable cells in 96-well plates without the need for cell counting; hence it is used to determine cytotoxicity of various drugs at different concentrations. The assay is based on the principle that mitochondrial activity remains almost constant for most of the viable cells. Therefore, the viable cell count is directly related to the mitochondrial activity. The results of cell viability assay using MTT dye are depicted in Figure 5. Control and the formulations (ITR-CLIN-loaded MM and Blank MM) did not show any toxicity till 100 µg/mL after 24 h of treatment indicating that all the excipients employed for the formulation of mixed micellar gel are safe to use without any cytotoxic effects. The differences in % cell viability between control and the developed formulations was non-significant; however, it was significant between control and pure drug (p < 0.05). The study concluded that the formulations are non-cytotoxic to HaCat cell lines [13,45].