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Therapeutic Methods and Therapies TCIM
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1.
Nutrients ; 14(14)2022 Jul 14.
Article in English | MEDLINE | ID: mdl-35889842

ABSTRACT

Although many natural products have proven their potential to regulate obesity through the modulation of adipocyte biology, none of them has yet been approved for clinical use in obesity therapy. This work aims to isolate valuable secondary metabolites from an orchid species (Dendrobium heterocarpum) and evaluate their possible roles in the growth and differentiation of 3T3-L1 pre-adipocytes. Six compounds were isolated from the orchid's methanolic extracts and identified as amoenylin (1), methyl 3-(4-hydroxyphenyl) propionate (2), 3,4-dihydroxy-5,4'-dimethoxybibenzyl (3), dendrocandin B (4), dendrofalconerol A (5), and syringaresinol (6). Among these phytochemicals, compounds 2, 3, and 6 exhibited lower effects on the viability of 3T3-L1 cells, offering non-cytotoxic concentrations of ≲10 µM. Compared to others tested, compound 3 was responsible for the maximum reduction of lipid storage in 3T3-L1 adipocytes (IC50 = 6.30 ± 0.10 µM). A set of protein expression studies unveiled that compound 3 at non-cytotoxic doses could suppress the expression of some key transcription factors in adipocyte differentiation (i.e., PPARγ and C/EBPα). Furthermore, this compound could deactivate some proteins involved in the MAPK pathways (i.e., JNK, ERK, and p38). Our findings prove that D. heterocarpum is a promising source to explore bioactive molecules capable of modulating adipocytic growth and development, which can potentially be assessed and innovated further as pharmaceutical products to defeat obesity.


Subject(s)
Dendrobium , 3T3-L1 Cells , Adipocytes , Adipogenesis , Animals , Cell Differentiation , Dendrobium/metabolism , Lipids/pharmacology , Methanol/pharmacology , Mice , Obesity/metabolism , PPAR gamma/metabolism , Plant Extracts/chemistry
2.
Article in English | MEDLINE | ID: mdl-34349823

ABSTRACT

Cancer stem-like cells (CSCs) are key mediators driving tumor initiation, metastasis, therapeutic failure, and subsequent cancer relapse. Thus, targeting CSCs has recently emerged as a potential strategy to improve chemotherapy. In this study, the anticancer activity and stemness-regulating capacity of 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum, are revealed in CSCs of various human lung cancer cells. Culture with TDB (5-10 µM) strongly abolished tumor-initiating cells in lung cancer H460, H23, and A549 cells in both anchorage-dependent and anchorage-independent colony formation assays. Through the 3D single-spheroid formation model, attenuation of self-renewal capacity was observed in CSC-enriched populations treated with 1-10 µM TDB for 7 days. Flow cytometry analysis confirmed the attenuation of %cell overexpressing CD133, a CSC biomarker, in TDB-treated lung cancer spheroids. TDB at 5-10 µM remarkably suppressed regulatory signals of p-Akt/Akt, p-GSK3ß/GSK3ß, and ß-catenin corresponding to the downregulated mRNA level of stemness transcription factors including Nanog, Oct4, and Sox2. Moreover, the antiapoptosis Bcl-2 and Mcl-1 proteins, which are downstream molecules of Akt signaling, were evidently decreased in CSC-enriched spheroids after culture with TDB (1-10 µM) for 24 h. Interestingly, the diminution of Akt expression by specific siAkt effectively reversed suppressive activity of TDB targeting on the CSC phenotype in human lung cancer cells. These findings provide promising evidence of the inhibitory effect of TDB against lung CSCs via suppression of Akt/GSK3ß/ß-catenin cascade and related proteins, which would facilitate the development of this bibenzyl natural compound as a novel CSC-targeted therapeutic approach for lung cancer treatment.

3.
Sci Rep ; 11(1): 4060, 2021 02 18.
Article in English | MEDLINE | ID: mdl-33603033

ABSTRACT

The limitations of cisplatin, a standard chemotherapy for lung cancer, have been documented with serious adverse effects and drug resistance. To address the need for novel therapy, this study firstly reveals the potential of peptide from Lentinus squarrosulus (Mont.) as a chemotherapeutic adjuvant for cisplatin treatment. The purified peptide from L. squarrosulus aqueous extracts was obtained after eluting with 0.4 M NaCl through FPLC equipped with anion exchange column. Preincubation for 24 h with 5 µg/mL of the peptide at prior to treatment with 5 µM cisplatin significantly diminished %cell viability in various human lung cancer cells but not in human dermal papilla and proximal renal cells. Flow cytometry indicated the augmentation of cisplatin-induced apoptosis in lung cancer cells pretreated with peptide from L. squarrosulus. Preculture with the peptide dramatically inhibited colony formation in lung cancer cells derived after cisplatin treatment. Strong suppression on integrin-mediated survival was evidenced with the diminution of integrins (ß1, ß3, ß5, α5, αV) and down-stream signals (p-FAK/FAK, p-Src/Src, p-Akt/Akt) consequence with alteration of p53, Bax, Blc-2 and Mcl-1 in cisplatin-treated lung cancer cells preincubated with peptide from L. squarrosulus. These results support the development of L. squarrosulus peptide as a novel combined chemotherapy with cisplatin for lung cancer treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cisplatin/pharmacology , Lentinula/chemistry , Lung Neoplasms/drug therapy , Peptides/therapeutic use , Plant Extracts/therapeutic use , Adjuvants, Pharmaceutic/pharmacology , Adjuvants, Pharmaceutic/therapeutic use , Blotting, Western , Cell Line, Tumor , Drug Synergism , Flow Cytometry , Humans , Peptides/isolation & purification , Peptides/pharmacology , Plant Extracts/pharmacology
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