Matrine reverses the drug resistance of K562/ADM cells to ADM and VCR via promoting autophagy

Abstract

Background: This study aimed to investigate the effects of matrine (MAT) on the drug resistance of K562/ ADM cells.Methods: K562/S and K562/ADM cells were treated with different concentrations of vincristine (VCR), adriamycin (ADM), and/or MAT for 48 h. The cell viability was determined by MTT assay, and the drugresistant multiple and drug-resistant reversal multiple were calculated based on half-inhibitory concentration (IC50). The cell apoptosis, as well as cell cycle were detected by flow cytometry. The autophagy was evaluated by transmission electron microscope and GFP-LC3 staining. Autophagy-related protein levels of LC3 II, and P62 were detected by Western blot.Results: MAT reduced the viability of K562/S and K562/ADM cells in a dose-dependent manner, and 0.5 mg/mL was identified as the non-cytotoxic concentration. MAT eliminated the drug resistance of K562/ ADM cells to ADM and VCR, and the drug resistance reversal multiple was 10.12 and 4.91, respectively. Chloroquine (CQ), a lysosomal inhibitor significantly reversed the inhibitory effect of MAT on the viability of K562/ADM cells. In addition, MAT induced the apoptosis of K562/ADM cells through arresting the cell cycle at G0/G1 phase in a dose-dependent manner. MAT also increased the autophagic vacuoles, the LC3+ punctate fluorescence, as well as the LC3 II protein level, and decreased P62 protein level in K562/ADM cells in a dose-dependent manner.Conclusions: MAT reversed the drug resistance of K562/ADM cells to ADM and VCR through promoting autophagy.

The Cytoprotective, Cytotoxic and Nonprotective Functional Forms of Autophagy Induced by Microtubule Poisons in Tumor Cells—Implications for Autophagy Modulation as a Therapeutic Strategy

“…Consistent with this view from the studies by Li et al [ 88 ] and Takahashi et al [ 89 ] reported that cotylenin A, which is a plant-growth regulator, in combination with vincristine, synergistically inhibited the growth of myeloma cells and induced apoptosis. Interestingly Cotylenin A with vincristine synergistically induced autophagy, as evidenced by LC3-II accumulation and p62/SQSTM1 degradation.…”

“…Li et al [ 88 ] studied the effects of Matrine (MAT) in the K562/ADM cell line. MAT is an alkaloid that sensitizes K562/ADM cells to Adriamycin and vincristine, and at the same time, promotes autophagy, as evidenced by autophagic vacuole accumulation, increased LC3 punctate fluorescence, increased LC3 II protein levels, and p62/SQSTM1 protein degradation.…”

“…CQ significantly reversed the sensitization mediated by MAT on the viability of K562/ADM cells. It was therefore suggested that MAT reverses drug resistance to Adriamycin and vincristine via promoting a cytotoxic form of autophagy [ 88 ].…”

Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective

“…Matrine is an active component of the botanical drug Sophora flavescens, which exhibits potent anti-tumor properties. Matrine targets ATGs and affects the cell cycle of tumor cells, enhancing the sensitivity of drug-resistant cells to vincristine (VCR) and adriamycin (ADM) [ 88 ].…”

“…The NPs andrographolide [ 59 ], α-hederin [ 62 ], jolkinolide B [ 63 ], PC3-15 [ 64 ], pristimerin [ 65 ], icariin [ 67 ], apigenin [ 69 ], tea polyphenol [ 70 ], genistein [ 71 ], phloretin [ 72 ], FMNT [ 73 ], rutin [ 74 ], berberine [ 86 , 87 ], matrine [ 88 ], ursolic acid [ 104 ], betulinic acid [ 90 ], triptolide [ 92 ], oleanolic acid [ 93 ], AGE [ 94 ], demethylzeylasteral [ 95 ], resveratrol [ 96 ], piceatannol [ 98 ], quercetin [ 99 ], hyperoside [ 100 ], scutellarin [ 101 ], chrysin [ 102 ], thymoquinone [ 103 ], tetrandrine [ 126 , 127 ], lycorine [ 134 ], carnosic acid [ 137 ], β-elemene [ 140 ], curcumin [ 141 ], luteolin [ 155 ], and epigallocatechin gallate [ 145 ] are associated with autophagy in tumor cells. These NPs can control autophagy in tumor cells such as those of the liver, pancreatic, gastric, breast, myeloma, lung, glioma, colorectal, ovarian, cervical, and oral malignancies, and thus combat drug resistance.…”