Isorhamnetin in Tsoong blocks Hsp70 expression to promote apoptosis of colon cancer cells

Abstract

The roots of Codonopis bulleynana Forest ex diels ( cb Fed), locally known as Tsoong, have been used as a tonic food. Tsoong has wide range of pharmacological effects, including anticancer efficacy. In the present study, the anticancer activity of Tsoong and its potential molecular mechanisms were investigated. Isorhamnetin, a flavonol aglycone, is important compound and metabolite in Tsoong. It can promote apoptosis of colon cancer cells through up-regulating apoptosis-related genes (Apaf1, Casp3 and Casp9) because it blocks Hsp70 genes (Hspa1a, Hspa1b and Hspa8). These were verified by in vitro and in vivo experiments. In vitro , cell counting kit-8 (CCK-8) assays and flow cytometry in HCT116 and SW480 colon cancer cell were used to assess the anti-proliferation and apoptosis-promoting activities of Tsoong. In vivo , the antitumor effect of Tsoong was assessed in colon cancer-bearing nude mice as a xenograft model. These results show that Isorhamnetin is very critical in Tsoong because Tsoong can down-regulate Hsp70 genes and promote apoptosis of colon cancer cells by inhibiting Hsp70 largely due to the efficacy of Isorhamnetin. Our results may ultimately help in the development of diagnostic and therapeutic strategies to control this devastating disease.

Polyphenol analysis using high‐resolution mass spectrometry allows differentiation of drought tolerant peanut genotypes

“…Procyanidins are related to a decrease in the risk of developing cardiovascular diseases . Isorhamnetins have anticancer activity and are known to promote the apoptosis of colon cancer cells, whereas quercetins are related to antidiabetic activity …”

“…Procyanidins are related to a decrease in the risk of developing cardiovascular diseases. 41 Isorhamnetins have anticancer activity and are known to promote the apoptosis of colon cancer cells, 42,43 whereas quercetins are related to antidiabetic activity. 44 Regardless of the method adopted, grouping analyses based on flavonoids were successful in identifying genotypes adapted to dry environments.…”

Anticancer Properties of Lobetyolin, an Essential Component of Radix Codonopsis (Dangshen)

“…The anticancer effect was associated with a higher level of inflammatory cell infiltration and a reduced level of tumor autophagy in vivo [ 51 ]. But recently, the anticancer activity of Tsoong was attributed, at least in part, to the flavonol aglycone isorhamnetin [ 52 ] and the phenylpropanoid cordifoliketone A [ 20 ] included in the extract. LBT may play a secondary role.…”

A Study on the Mechanism of Herbal Drug FDY003 for Colorectal Cancer Treatment by Employing Network Pharmacology

“…82 The anti-growth and death-promoting functions of isorhamnetin are mediated through the heat shock protein (Hsp)-70, caspase, Src, β-catenin, and PI3K-Akt-mammalian target of rapamycin (mTOR) pathways. [83][84][85] Kaempferol induces growth-arrest, death, and chemosensitization of CRC cells and tumors by targeting reactive oxygen species (ROS), p38, p53, PARP, p21, Bax, Bcl-2, thymidylate synthase (TS), phosphatase and tensin homolog (PTEN), PI3K-Akt, polypyrimidine-tract binding protein 1 (PTBP1)-pyruvate kinase M2 (PKM2), TNF-related apoptosis-inducing ligand (TRAIL)/DR-5, FAS, cyclin-dependent kinases (CDKs), cyclins, MAPK, Janus kinase (JAK)-signal transducers and activators of transcription (STAT), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), PUMA, ataxia telangiectasia mutated (ATM), H2A histone family member X (H2AX), insulinlike growth factor 2 (IGF-2), histidine-rich glycoprotein (HRG), insulin-like growth factor 1-receptor (IGF-1R), ErbB3, MMP, VEGF, nitric oxide (NO), and PGE-2 signaling. [86][87][88][89][90][91][92][93][94][95] Luteolin modulates various cascades, [eg, MAPK, heme oxygenase-1 (HO-1), AMPK, Peroxisome Proliferator-Activated Receptor (PPAR)-γ/organic anion/cation transporter (OCTN)-2, calpain, ubiquitin like with PHD and ring finger domains 1 (UHRF1), DNA methyltransferase 1 (DNMT1), CREB, miR-384/pleiotrophin, cyclin, Wnt, β-catenin, glycogen synthase kinase (GSK)-3β, glutathione (GSH), nuclear factor erythroid 2-related factor 2 (Nrf2), HIF-1, IGF-2, IGF-1R, PI3K-Akt-mTOR, ERK, cell division cycle 25C (CDC25c), forkhead box transcription factor (FoxO), Beclin-1, PARP, Bcl-2, Bax, caspase, autophagy related 5 (Atg5), microtubule-associated protein 1 light chain 3B (LC3B)-I/II, focal adhesion kinase (Fak), Bim, BAD, N-cadherin, sphingosine kinase (Sphk)-1/Sphk-2, Sry-related HMG box (Sox), transient receptor potential vanilloids (TRPVs), VEGF, CDKs, p21, PARP, survivin, p21, myeloid cell leukemia (Mcl)-1, B-cell lymphoma-extra-large (Bcl-xL), mouse double minute 2 homolog (MDM2), Cox-2, MMPs, and tissue inhibitor metalloproteinase-2 (TIMP-2) cascades] to inhibit EMT, growth, carcinogenesis, migration, chemoresistance, invasion, survival, and metastasis of CRC cells and tumors.…”