Total steroidal saponins from black nightshade (Solanum nigrum L.) overcome tumor multidrug resistance by inducing autophagy-mediated cell death in vivo and in vitro
Yi Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorSiyu Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorCorresponding Author
Jingwen Xu
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Correspondence
Xiangjiu He and Jingwen Xu, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Email: [email protected] and [email protected]
Search for more papers by this authorYihai Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorLimin Xiang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorCorresponding Author
Xiangjiu He
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Correspondence
Xiangjiu He and Jingwen Xu, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Email: [email protected] and [email protected]
Search for more papers by this authorYi Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorSiyu Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorCorresponding Author
Jingwen Xu
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Correspondence
Xiangjiu He and Jingwen Xu, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Email: [email protected] and [email protected]
Search for more papers by this authorYihai Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorLimin Xiang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Search for more papers by this authorCorresponding Author
Xiangjiu He
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China
Guangdong Engineering Research Center for Lead Compounds & Drug Discovery, Guangzhou, China
Correspondence
Xiangjiu He and Jingwen Xu, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Email: [email protected] and [email protected]
Search for more papers by this authorAbstract
Multiple drug resistance (MDR) often occurs after prolonged chemotherapy, leading to refractory tumors and cancer recurrence. In this study, we demonstrated that the total steroidal saponins from Solanum nigrum L. (SN) had broad-spectrum cytotoxic activity against various human leukemia cancer cell lines, especially in adriamycin (ADR)-sensitive and resistant K562 cell lines. Moreover, SN could effectively inhibit the expression of ABC transporter in K562/ADR cells in vivo and in vitro. In vivo, by establishing K562/ADR xenograft tumor model, we demonstrated that SN might overcome drug resistance and inhibit the proliferation of tumors by regulating autophagy. In vitro, the increased LC3 puncta, the expression of LC3-II and Beclin-1, and the decreased expression of p62/SQSTM1 in SN-treated K562/ADR and K562 cells demonstrated autophagy induced by SN. Moreover, using the autophagy inhibitors or transfecting the ATG5 shRNA, we confirmed that autophagy induced by SN was a key factor in overcoming MDR thereby promoting cell death in K562/ADR cells. More importantly, SN-induced autophagy through the mTOR signaling pathway to overcome drug resistance and ultimately induced autophagy-mediated cell death in K562/ADR cells. Taken together, our findings suggest that SN has the potential to treat multidrug-resistant leukemia.
CONFLICT OF INTEREST
The authors declare no competing financial interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ptr7796-sup-0001-supinfo.docxWord 2007 document , 135.4 KB | TABLE S1. Reagents. TABLE S2. Antibodies. FIGURE S1. Statistics of GFP-LC3 puncta from Figures 5c and 6a. (A and B) The number of GFP-LC3 puncta per cell was counted by Image J software from 6 different fields. The experiment was repeated for three individual studies. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to control group, #p < 0.05 compared to SN-treated group. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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