Chemotherapy is one of the major treatment methods for cancer However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance Management of drug resistance is important towards successful chemotherapy There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities We summarized the reports into four categories: (1) in vitro studies using cell line models; (2) serum pharmacology; (3) in vivo studies using animal models; and (4) clinical studies Fourteen single compounds were reported to have antidrug resistance activity for the first time In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance

/pdf/overcome-cancer-cell-drug-resistance-using-natural-products-29c2h828lw.pdf

Overcome Cancer Cell Drug Resistance Using Natural Products

Multi-drug resistance (MDR) of cancer cells severely limits therapeutic outcomes. A proposed mechanism for MDR involves the efflux of anti-cancer drugs from cancer cells, primarily mediated by ATP-binding cassette (ABC) membrane transporters including P-glycoprotein. This article reviews the recent progress of using active ingredients, extracts and formulae from Chinese medicine (CM) in circumventing ABC transporters-mediated MDR. Among the ABC transporters, Pgp is the most extensively studied for its role in MDR reversal effects. While other MDR reversal mechanisms remain unclear, Pgp inhibition is a criterion for further mechanistic study. More mechanistic studies are needed to fully establish the pharmacological effects of potential MDR reversing agents.

/pdf/circumvention-of-multi-drug-resistance-of-cancer-cells-by-tf1j1gczy2.pdf

Circumvention of multi-drug resistance of cancer cells by Chinese herbal medicines

P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the mechanism by which imperatorin promotes P-gp-mediated drug transport. We used molecular docking to predict the binding force between imperatorin and P-gp and the effect of imperatorin on P-gp activity. P-gp efflux activity and P-gp ATPase activity were measured using a rhodamine 123 (Rh-123) accumulation assay and a Pgp-Glo™ assay; respectively. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess cellular membrane fluidity in MDCK-MDR1 cells. Western blotting was used to analyze the effect of imperatorin on P-gp expression; and P-gp mRNA levels were assessed by qRT-PCR. Molecular docking results demonstrated that the binding force between imperatorin and P-gp was much weaker than the force between P-gp and verapamil (a P-gp substrate). Imperatorin activated P-gp ATPase activity; which had a role in the inhibition of P-gp activity. Imperatorin promoted Rh-123 accumulation in MDCK-MDR1 cells and decreased cellular membrane fluidity. Western blotting demonstrated that imperatorin inhibited P-gp expression; and qRT-PCR revealed that imperatorin down-regulated P-gp (MDR1) gene expression. Imperatorin decreased P-gp-mediated drug efflux by inhibiting P-gp activity and the expression of P-gp mRNA and protein. Our results suggest that imperatorin could down-regulate P-gp expression to overcome multidrug resistance in tumors.

https://www.mdpi.com/1420-3049/21/12/1606/pdf

Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport

Summary Dauricine has a variety of pharmacological properties including anti-inflammatory, anti-arrhythmic, and antihypertensive effects as well as reversing multidrug resistance (MDR) of cancer cells. While its therapeutic application is increasing, its bioavailability of different administration routes has not been studied. In the present study, we developed and validated a liquid chromatography/electrospray ionization mass spectrometry method (LC-MS/MS). Using this method, we quantified dauricine in rat plasma after administration via intravenous (i.v.) injection, per oral (p.o.), and intraperitoneal injection (i.p.). Our results indicated that this method detected plasma dauricine with a good linearity in the range of 1.95–1000.00 ng/mL (r = 0.9997). The extraction method showed an average intra- and inter-day recovery of 98.21–104.35% and 98.0–103.58%, respectively. Dauricine showed a fast absorption and widespread distribution after administration in all three tested routes. After intravenous admini...

Using LC-MS/MS to study dauricine pharmacokinetics and determine its bioavailability following administration in different routes

Phenolic alkaloids from Menisphermum dauricum (PAMD) was a compound of multiple fat soluble alkaloid extracted from Rhizoma Menispermi. PAMD had wide pharmacological effects including of anti-arrhythmia, anti-MI, anti-thrombosis, anti-dementia, anti-cancer, anti-inflammatory, inhibiting respiratory depression, influencing on heart electrophysiology, ptotecting heart and nerve after cerebral ischemia, suppressing pain, lowering blood pressure, improving learning disorder and so on.

Pharmacology Research Progress of Phenolic Alkaloids from Menisphermum dauricum

Object: To find effective herb medicine having the potency of reversing multidrug resistance (MDR) Method:Dauricine, one kind of herd medicine,has been selected to study its reversal effect to K562/ADM cell line comparing with verapamil as positive control Results:Dauricine can reduce the value of IC50 of adrimycin and incristine against MDR cell line K562/ADM at non-cytotoxic concentration and enhance accumulation of adriamycin and daunorubicin, but cause no change in the expression of P-170Conclusion:Dauricine can reverse MDR of K562/ADM to some extent

Li Jianhua

Papers

Reversal of multidrug resistance in human K562/ADM cell line by dauricine