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Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
Mechanistically, treatment with SAHA reduced phosphorylated Akt/FOXO3a signaling thereby promoted apoptosis in prostate cancer cell lines DU145 and PC-3 (Shi et al., 2017). Additional studies have shown that SAHA can prevent the early-stage melanocytic lesion development in skin; hence, several derivatives of SAHA containing selenium were prepared and tested for safety and efficacy in cultured cells and in xenografted animals (Gowda et al., 2012). In small-cell lung cancer lines NCI-H520, NCI-H460, NCI-H522, NCI-H1299 AND SK-MES-1, addition of SAHA blocked cell growth at G0/G1 and G2/M phases (Asgar et al., 2016). Future studies should focus on combining Vorinostat—along with other chemotherapeutic drugs—to identify a synergistically acting combination therapy for treating cancers. Initial studies in this direction are currently under progress (Suraweera et al., 2018).
Introduction to Bioresponsive Polymers
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Deepa H. Patel, Drashti Pathak, Neelang Trivedi
The novel use of reducible hyperbranched (rHB) polymers for delivery of RNA interference (RNAi) therapeutics. Cationic poly(amidoamine) hyperbranched polymers that enclose different contents of reducible disulfide to nonreducible linkages (0%, 17%, 25%, and 50%) were employed to form inter polyelectrolyte polyplexes with small interfering RNA (siRNA) and precursor microRNA (miRNA). The rHB complexes of ~100 nm in size, which revealed redox-activated disassembly in the presence of dithiothreitol (DTT). The complexes were keenly internalized and showed no cellular toxicity in an endogenous improved green fluorescence protein (EGFP) expressing H1299 human lung cancer cell line. The highest specific enhanced green fluorescent protein (EGFP) gene silencing (~75%) was accomplished with rHB (17%)/siRNA complexes at a weight-to-weight (w/w) ratio of 40 that associated with the capability for this polymer to effectively transfect pre-miRNA. The role of particle disassembly for intracellular targeting and modulation of gene silencing addressed in this work are significant considerations in the development of this and other next-generation delivery systems.
Essential Oils in Cancer Therapy
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Carmen Trummer, Gerhard Buchbauer
Populus alba L. (Salicaceae) and Rosmarinus officinalis L. (Lamiaceae) EO of leaves and flowers were evaluated for their cytotoxic effects (Gezici et al., 2017). The EOs of these medicinal and aromatic plants were obtained by hydrodistillation, and about 300 compounds were identified. The used cell lines were A549 (human lung adenocarcinoma), H1299 (human non-small cell lung cancer), MCF-7 (human breast adenocarcinoma), and non-tumor HUVEC cells. R. officinalis exerted stronger inhibitory effects than P. alba. Calculated IC50 values for R. officinalis were ranging from 3.06 to 7.38 μg/mL and for P. alba from 12.05 to 28.16 μg/mL. The highest activity was achieved on A459 and H1299 cells, while only moderate activity was exhibited against MCF-7 cells. The significant growth inhibition effect of R. officinalis may be attributed to the presence of carnosol, methyl carnosate, carnosic, and rosmarinic acids.
ELANE Promotes M2 Macrophage Polarization by Down-Regulating PTEN and Participates in the Lung Cancer Progression
Published in Immunological Investigations, 2023
Sinuo Song, Yunping Zhao, Tianyu Fu, Yunfei Fan, Jie Tang, Xiaoxing Wang, Chao Liu, Xiaobo Chen
Human THP-1 monocytes (ZQ0086) were purchased from Shanghai Zhong Qiao Xin Zhou Biotechnology Co., Ltd., and cultured in RPMI-1640 medium (Shanghai Zhong Qiao Xin Zhou Biotechnology Co., Ltd.) at 37℃ in a 5% CO2 incubator. Human lung cancer cell lines A549 and H1299 were purchased from the Cell Bank of the Chinese Academy of Sciences. The THP-1 monocytes were divided into M0, M2, and M2+ELANE (20, 40, 80, and 200 nM) groups. M0 group: The THP-1 monocytes were added to 2 mL of RPMI-1640 complete medium containing 320 nM phorbol-12-myristate-13-acetate (PMA; PeproTech), then transferred to 6-well plates at a density of 1 × 106 cells/well, and induced differentiation for 24 h. M2 group: The THP-1 monocytes were treated with 320 nM PMA for 6 h, then cultured with interleukin-4 (IL-4) and IL-13 (20 ng/mL; Cyagen Biosciences) for 18 h. M2+ELANE group: The THP-1 monocytes were treated with 320 nM PMA for 6 h, then cultured with IL-4 and IL-13 (20 ng/mL) and 20, 40, 80, and 200 nM ELANE for 18 h. Conditioned medium (CM) of macrophages in different groups were collected and co-cultured with A549 or H1299 cells for 24 h. Anti-ELANE antibody NP57 (ab254178; abcam) (80 nM) was added to the collected CM to neutralize ELANE and exclude the direct effect of ELANE on the lung cancer cells. The A549 or H1299 cells were divided into control, M0-CM, M2-CM, and (M2+ELANE)-CM groups.
Circ-METTL15 contributes to the proliferation, metastasis, immune escape and restrains apoptosis in lung cancer by regulating miR-1299/PDL1 axis
Published in Autoimmunity, 2022
Rui Zhang, Liang Shang, Jinniang Nan, Kai Niu, Jixin Dai, Xintian Jin, Xianghua Zhang
In order to investigate the function of miR-1299 in lung cancer development and whether PDL1 was involved, H1299 and A549 cells were introduced with miR-NC, miR-1299, miR-1299 + pcDNA or miR-1299 + PDL1. As exhibited in Figure 6(A), PDL1 expression was obviously downregulated by miR-1299 overexpression and upregulated again by PDL1 introduction, which validated the transfection efficacy of PDL1. As exhibited in Figure 6(B–E), miR-1299 overexpression distinctly repressed the proliferation of H1299 and A549 cells by decreasing cell viability, clone ability and the rates of EDU positive cells, which was mitigated via PDL1 overexpression. Meanwhile, miR-1299 addition evidently promoted cell apoptosis, which was weakened by PDL1 upregulation (Figure 6(F)). And miR-1299 overexpression markedly repressed cell invasion, which was attenuated via PDL1 restoration (Figure 6(G)). Moreover, miR-1299 overexpression obviously declined the immune-suppressive effect of H1299 and A549 cells, which was reversed via PDL1 overexpression (Figure 6(H–J)). Additionally, Bcl-2 and CyclinD1 expression levels were inhibited by miR-1299 addition, while the effect was relieved by PDL1 introduction (Figure 6(K,L)). Therefore, it was deemed that miR-1299 could hamper the proliferation, metastasis and immune escape by decreasing PDL1 expression in lung cancer cells.
Circ_0000735 enhances the proliferation, metastasis and glycolysis of non-small cell lung cancer by regulating the miR-635/FAM83F axis
Published in Experimental Lung Research, 2021
Guigang Tai, Miao Zhang, Fang Liu
Subsequently, the biological functions of A549 and H1299 cells was evaluated. Function experiments showed that the inhibitory effect of circ_0000735 knockdown on the viability and clonal formation numbers of A549 and H1299 cells could be abolished by miR-635 inhibitor (Figure 4A–C). Also, miR-635 inhibitor could reverse the suppressive effect of circ_0000735 silencing on the migration and invasion of A549 and H1299 cells (Figure 4D,E). Furthermore, the apoptosis rate promoted by circ_0000735 silencing also was overturned by miR-635 inhibitor (Figure 4F). Additionally, the decreasing effect of circ_0000735 knockdown on glucose consumption, lactate production, and the protein levels of HK2 and LDHA also could be reversed by miR-635 inhibitor (Figure 4G–J). These data confirmed that circ_0000735 sponged miR-635 to regulate NSCLC progression.