Apoptotic and autophagic death union by Thuja occidentalis homeopathic drug in cervical cancer cells with thujone as the bioactive principle  

作　　者：Asmita Pal Sucharita Das Soumalee Basu Rita Kundu 

机构地区：[1]Department of Botany,University of Calcutta,Kolkata,West Bengal 700019,India [2]Department of Microbiology,University of Calcutta,Kolkata,West Bengal 700019,India

出　　处：《Journal of Integrative Medicine》2022年第5期463-472,共10页结合医学学报（英文版）

基　　金：This work has been funded by University Grants Commission-University with Potential for Excellence Phase II grant from Government of India(sanction No.UCC/144/UPE/ST1).

摘　　要：Objective‘Multi-targeting’drugs can prove fruitful to combat drug-resistance of multifactorial disease—cervical cancer.This study envisioned to reveal if Thuja homeopathic mother tincture(MT)and its bioactive component could combat human papillomavirus(HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts.Methods Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species(ROS)generation by 2’,7’-dichlorodihydrofluorescein diacetate(DCFDA)staining and loss in mitochondrial membrane potential(MMP)by rhodamine(Rh)123 staining.Apoptosis and autophagy inductions were studied by acridine orange(AO)ethidium bromide(EB)staining and immunoblot analyses of marker proteins.The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency.Results Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50%inhibitory concentration(IC50)dosage of 17.3μL/mL.An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MMP respectively.AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways—apoptosis and autophagy.Immunoblots showed cleavage of caspase-3 and poly adenosine diphosphate-ribose polymerase-1(PARP-1)along with upregulation of Beclin-1,microtubule-associated protein 1 light chain 3B(LC3B)-II,and p62 proteins.Hence,the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage,while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins.Thujone,detected as the bioactive principle of Thuja MT showed greater anti-proliferative and anti-migratory poten

关 键 词：Thuja HOMEOPATHY Thujone Cervical cancer Apoptosis-autophagy crosstalk 

分 类 号：R285[医药卫生—中药学]