Abstract
Background
Polyphyllin I (PPI), a steroidal saponin, exhibits antitumor activity and chemosensitization effect for a broad spectrum of cancer cells, however, its toxicity and chemosensitization effect in vivo is still unknown.
Objective
We investigated PPI’s cytotoxic activity, toxicity and chemosensitization effect and in vitro and in vivo.
Results
The IC50 values of PPI on MCF-7, H22, and S180 tumor cells were 4.37 µmol/L, 1.71 µmol/L, and 0.92 µmol/L, respectively. The LD50 of PPI was found to be 47.9 mg/kg using ip. injection. PPI at concentrations of 0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg, and 2.4 mg/kg (1/80 LD50–1/20 LD50) were synergized with DOX of 0.5 mg/kg to inhibit the H22 and S180 tumor growth in vivo by inducing apoptosis without obvious immunotoxicity. PPI exhibited a remarkable hemolytic effect on rabbit erythrocytes (EC50 = 4.3 µM), while it had no impact in mice.
Conclusion
Our study revealed that the PPI-sensitized chemotherapeutic effect, when used in safe doses, circumvents immunotoxic side effects of DOX in vivo; thus, helping future clinical research.
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Abbreviations
- PPI:
-
Polyphyllin I
- DOX:
-
Doxorubicin
- NS:
-
Normal saline
- MTT:
-
3-(4, 5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide
- ip.:
-
Intraperitoneal
- HE:
-
Hematoxylin–eosin
- TUNEL:
-
TdT-mediated dUTP nick-end labeling
- ALP:
-
Alkaline phosphatase
- RBC:
-
Red blood cell
- TBILT:
-
Total bilirubin
- DBILT:
-
Direct bilirubin
- IBILT:
-
Indirect bilirubin
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (No. 81960739 and 32070361), by grants from the Joint Application and Basic Research Foundation of Kunming Medical University & Science and Technology Department of Yunnan Province of China (grant no. 2019FE001(-193) and 202001AY070001–180), Yunnan Major Biopharmaceutical Project (grant no. 2018ZF002), Digitalization, development, and application of biotic resources of Kunming Medical University (202002AA100007), the seventh batch of Yunnan specialty plant polysaccharide engineering research center construction plan (2019–57) and Innovative Research Team Program in Science and Technology in Kunming Medical University (CXTD202003).
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Z-X, N-X, Z-YQ, X-YAT, C-DY, M-JQ, Z-Y and Y-FH involved in design, data collection, writing, and revising the manuscript. Z-YP, Z-X, N-X, Z-YQ and Y-HZ involved in conception, design, literature review, writing the manuscript. Z-YP and W-YH involved in design, writing, revising the manuscript. In addition, all the authors have read and approved the final manuscript.
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The authors declare that they have no competing interests. The author Xiang Zhu declares that he has no conflict of interest; the author Xin Na declares that he has no conflict of interest; the author Yueqin Zeng declares that she has no conflict of interest; the author Yangantai Xu declares that he has no conflict of interest; the author Dongya Chai declares that she has no conflict of interest; the author Huanzhi Yang declares that she has no conflict of interest; the author Jingqian Miao declares that she has no conflict of interest; the author Yuan Zhang declares that she has no conflict of interest; the author Fenghua Yang declares that she has no conflict of interest; the author Yuehu Wang declares that he has no conflict of interest; the author Yiping Zhou declares that she has no conflict of interest.
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All the animal experiments were conducted following the guidelines of China Council on Animal Care and Use. The study was approved by Ethical Committee of Kunming Medical University.
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Zhu, X., Na, X., Zeng, Y. et al. Polyphyllin I combined with doxorubicin shows chemosensitization effect in vivo and reduces immunotoxicity of doxorubicin. Mol. Cell. Toxicol. 18, 359–369 (2022). https://doi.org/10.1007/s13273-021-00206-w
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DOI: https://doi.org/10.1007/s13273-021-00206-w