1.Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways.
Jing H1, Sun W2, Fan J1, Zhang Y3, Yang J1, Jia J1, Li J1, Guo J1, Luo S4, Zheng Y1. Mol Med Rep. 2016 Apr;13(4):3009-16. doi: 10.3892/mmr.2016.4917. Epub 2016 Feb 19.
Shikonin, which is a major ingredient of the traditional Chinese herb Lithospermum erythrorhizon, possesses various biological functions, including antimicrobial, anti-inflammatory, and antitumor activities. The present study aimed to determine the molecular mechanisms underlying the effects of shikonin on HaCaT cell apoptosis. Treatment with shikonin significantly inhibited the viability of HaCaT cells in a dose‑ and time‑dependent manner, and promoted cell cycle arrest at G0/G1 phase and apoptosis. In addition, shikonin treatment reduced the mitochondrial membrane potential and induced reactive oxygen species generation. The results of a western blot analysis demonstrated that shikonin significantly activated caspase 3 expression, downregulated B‑cell lymphoma 2 (Bcl‑2) expression, and upregulated Bcl‑2‑associated X protein and Bcl‑2 homologous antagonist killer expression in a dose‑dependent manner in HaCaT cells. Furthermore, shikonin decreased extracellular signal‑regulated kinase (Erk) and Akt phosphorylation.
2.Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.
Chopra D1, Ray L2, Dwivedi A2, Tiwari SK3, Singh J3, Singh KP2, Kushwaha HN2, Jahan S3, Pandey A2, Gupta SK4, Chaturvedi RK3, Pant AB5, Ray RS6, Gupta KC7. Biomaterials. 2016 Apr;84:25-41. doi: 10.1016/j.biomaterials.2016.01.018. Epub 2016 Jan 11.
Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs.
