Flavored Guilu Erxian decoction inhibits the injury of human bone marrow mesenchymal stem cells induced by cisplatin
Corresponding Author(s) : Lin Shi
Cellular and Molecular Biology,
Vol. 64 No. 6: Advances in mechanism and treatment strategy of cancer
Abstract
To examine the exact role of flavored Guilu Erxian decoction, a Traditional Chinese Medicine (TCM) in the treatment of cisplatin-induced side-effects in bone marrow mesenchymal stem cells (BM-MSCs). BM-MSCs were isolated from bone marrow collected from SD rats and identified by flow cytometry. Cells were cultivated in MEM alpha medium containing 5% (TCM-L), 10% (TCM-M) and 20% (TCM-H) dosages of flavored Guilu Erxian decoction with or without cisplatin. Cell viability was determined through CCK-8 and thymidine analog 5-ethynyl-2"²-deoxyuridine (EdU) staining assay. Flow cytometry was used to determine cell cycle and apoptosis. The expression of p21 and cleaved-caspase-3 were examined using Western blot assay. The PI3K-AKT-mTOR pathway associated proteins, including p-PI3K, p-AKT and p-mTOR, were also examined by Western blot assay. CCK-8 and EdU staining assay demonstrated that cisplatin could inhibit cell proliferation in BM-MSCs in a dose and time dependent manner. Further, cisplatin could induce apoptosis through increasing G0/G1 cell cycle arrest, p21 and cleaved-caspase-3 expression. However, these phenomena would be significantly alleviated when adding the serum containing flavored Guilu Erxian decoction. Furthermore, the PI3K-AKT-mTOR pathway activation could be inhibited by cisplatin in BM-MSCs, while flavored Guilu Erxian decoction treatment successfully abrogated this effect. Combination of flavored Guilu Erxian decoction and cisplatin could reduce the damage to BM-MSCs. This indicates that the flavored Guilu Erxian decoction can enhance the possibility of BM-MSCs repairing and rehabilitating the normal function of injured tissues induced by cisplatin, which could provide a new direction for therapeutic applications.
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- Kodama A WH, Tanaka R, et al. Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephrotoxicity. Biochimica et Biophysica Acta 2014; 1840: 1152-1162.
- Lebwohl D CR. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. European Journal of Cancer 1998; 34(10): 1522 - 1534.
- Shiraishi F CL, Truong L, et al. Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. American Journal of Physiology: Renal Physiology 2000; 278(5): F726- F736.
- Abolfazl Avan TJP, et al. Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future. Oncologist 2015; 20(4 ): 411–432.
- Steyger. TKaPS. An integrated view of cisplatin-induced nephrotoxicity and ototoxicity. Toxicology Letters 2015; 237: 219-227.
- Kunter U RS, Djuric Z, et al. Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol 2006; 17(8): 2202–2212.
- A. C. Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer 2011; 71: 3–10.
- Galluzzi L VI, Michels J, et al Systems biology of cisplatin resistance: past, present and future. Cell Death Dis 2014; 5: e1257.
- Agung M. OM, Yanada S., et al. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc 2006; 14: 1307–1314.
- Ohishi M. SE. Bone marrow mesenchymal stem cells. J Cell Biochem 2010; 109: 277–282.
- Kucerova L SS. Tumor microenvironment and the role of mesenchymal stromal cells. Neoplasma 2013; 60(1): 1–10.
- Brooke G CM, Blair C, et al. Therapeutic applications of mesenchymal stromal cells. Semin Cell Dev Biol 2007; 18: 846–858
- DJ. P. Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Mol Ther 2009; 17: 939–946
- Uccelli A ML, and Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8: 726–736.
- Goldstein RH RM, Anderson K, et al. Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis. Cancer Res 2010; 70: 10044–10050.
- Chaturvedi P GD, Wong CC, et al. Hypoxiainducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest 2013; 123: 189–205.
- Torsvik A BR. Mesenchymal stem cell signaling in cancer progression. Cancer Treat Rev 2013; 39: 180-188.
- Abd-Allah S.H. SSM, Pasha H.F., et al. Mechanistic action of mesenchymal stem cell injection in the treatment of chemically induced ovarian failure in rabbits. Cytotherapy 2013; 15: 64–75.
- Kilic S. PF, Ozogul C.,et al. Protection from cyclophosphamide-induced ovarian damage with bone marrow-derived mesenchymal stem cells during puberty. Gynecol Endocrinol 2013; 30: 135–140.
- Herrera MB BB, Bruno S, et al. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 2004; 14(6): 1035–1041.
- Eisenberg DM DR, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. Journal of the American Medical Association 1998; 280(18): 1569–1575.
- K. C. Progress in traditional Chinese medicine. Trends Pharmacol Sci 1995; 16: 182–187.
- J. Q. Traditional medicine: a culture in the balance. Nature 2007; 448: 126–128.
- D. N. The new face of traditional Chinese medicine. Science 2003; 299: 188–190.
- Dominici M LBK, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-317.
- A. Kodama HW, R. Tanaka et al. Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephro-toxicity. Biochimica et Biophysica Acta 2014; 1840: 1152-1162.
- Johnson SM GP, Rampy BA, et al. Novel expression patterns of pi3k/AKT/mtor signaling pathway components in colorectal cancer. J Am Coll Surg 2010; 210: 767–768.
- King D YD, Bryant HE. Pi3king the lock: Targeting the pi3k/AKT/mtor pathway as a novel therapeutic strategy in neuroblastoma. J Pediatr Hematol Oncol 2015; 37: 245–251.
- Ou Y. ZD, Wu N., et al. Downregulation of miR-363 increases drug resistance in cisplatin-treated HepG2 by dysregulating Mcl-1. Gene 2015; 572(1): 116–122.
- Agarwal R. KSB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer 2003; 3: 502-516.
- Ning Yu YXCW. Bu-Zhong-Yi-Qi Decoction, the Water Extract of Chinese Traditional Herbal Medicine, Enhances Cisplatin Cytotoxicity in A549/DDP Cells through Induction of Apoptosis and Autophagy Biomed Res Int 2017; 2017: 3692797.
- Zhi-Ying Teng X-LC, Xue-Ting Cai, et al. Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity. Sci Rep 2015; 5: 15592.
- J. S. Immune regulation by mesenchymal stem cells:two sides to the coin. Tissue Antigens 2007; 69(1): 1-9.
- Guo J.Q. GX, Lin Z.J., et al. BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause. BMC Cell Biol 2013; 14: 1–9.
- Santos N. CC, Martins N., et al. Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol 2007; 81: 495-504.
- Z.H. S. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22: 7265-7279.
- Fu X HY, Xie C, et al. Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage. Cytotherapy 2008; 10: 353–363.
- L. K. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7: 573–584.
- Zangen R RE, Sidransky D. DeltaNp63α levels correlate with clinical tumor response to cisplatin. Cell Cycle 2005; 4: 1313–1315.
- Zhang R NY, Zhou Y. Increase the cisplatin cytotoxicity and cisplatin-induced DNA damage in HepG2 cells by XRCC1 abrogation related mechanisms. Toxicol Lett 2010; 192(2): 108-114.
- ZH S. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22(47): 7265-7279.
- Kumar S YC, Tchounwou PB. Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells. J Exp Clin Cancer Res 2014 33: 42.
- Yedjou CG TP. Modulation of p53, c-fos, RARE, cyclin A, and cyclin D1 expression in human leukemia (HL-60) cells exposed to arsenic trioxide. Mol Cell Biochem 2009 331: 207-214.
- Tchounwou SKPB. Molecular mechanisms of cisplatin cytotoxicity in acute promyelocytic leukemia cells. Oncotarget 2015; 6(38): 40734-40746.
- Jordan P C-FM. Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci 2000; 57: 1229-1235.
References
Kodama A WH, Tanaka R, et al. Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephrotoxicity. Biochimica et Biophysica Acta 2014; 1840: 1152-1162.
Lebwohl D CR. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. European Journal of Cancer 1998; 34(10): 1522 - 1534.
Shiraishi F CL, Truong L, et al. Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. American Journal of Physiology: Renal Physiology 2000; 278(5): F726- F736.
Abolfazl Avan TJP, et al. Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future. Oncologist 2015; 20(4 ): 411–432.
Steyger. TKaPS. An integrated view of cisplatin-induced nephrotoxicity and ototoxicity. Toxicology Letters 2015; 237: 219-227.
Kunter U RS, Djuric Z, et al. Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol 2006; 17(8): 2202–2212.
A. C. Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer 2011; 71: 3–10.
Galluzzi L VI, Michels J, et al Systems biology of cisplatin resistance: past, present and future. Cell Death Dis 2014; 5: e1257.
Agung M. OM, Yanada S., et al. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc 2006; 14: 1307–1314.
Ohishi M. SE. Bone marrow mesenchymal stem cells. J Cell Biochem 2010; 109: 277–282.
Kucerova L SS. Tumor microenvironment and the role of mesenchymal stromal cells. Neoplasma 2013; 60(1): 1–10.
Brooke G CM, Blair C, et al. Therapeutic applications of mesenchymal stromal cells. Semin Cell Dev Biol 2007; 18: 846–858
DJ. P. Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Mol Ther 2009; 17: 939–946
Uccelli A ML, and Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8: 726–736.
Goldstein RH RM, Anderson K, et al. Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis. Cancer Res 2010; 70: 10044–10050.
Chaturvedi P GD, Wong CC, et al. Hypoxiainducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest 2013; 123: 189–205.
Torsvik A BR. Mesenchymal stem cell signaling in cancer progression. Cancer Treat Rev 2013; 39: 180-188.
Abd-Allah S.H. SSM, Pasha H.F., et al. Mechanistic action of mesenchymal stem cell injection in the treatment of chemically induced ovarian failure in rabbits. Cytotherapy 2013; 15: 64–75.
Kilic S. PF, Ozogul C.,et al. Protection from cyclophosphamide-induced ovarian damage with bone marrow-derived mesenchymal stem cells during puberty. Gynecol Endocrinol 2013; 30: 135–140.
Herrera MB BB, Bruno S, et al. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 2004; 14(6): 1035–1041.
Eisenberg DM DR, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. Journal of the American Medical Association 1998; 280(18): 1569–1575.
K. C. Progress in traditional Chinese medicine. Trends Pharmacol Sci 1995; 16: 182–187.
J. Q. Traditional medicine: a culture in the balance. Nature 2007; 448: 126–128.
D. N. The new face of traditional Chinese medicine. Science 2003; 299: 188–190.
Dominici M LBK, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-317.
A. Kodama HW, R. Tanaka et al. Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephro-toxicity. Biochimica et Biophysica Acta 2014; 1840: 1152-1162.
Johnson SM GP, Rampy BA, et al. Novel expression patterns of pi3k/AKT/mtor signaling pathway components in colorectal cancer. J Am Coll Surg 2010; 210: 767–768.
King D YD, Bryant HE. Pi3king the lock: Targeting the pi3k/AKT/mtor pathway as a novel therapeutic strategy in neuroblastoma. J Pediatr Hematol Oncol 2015; 37: 245–251.
Ou Y. ZD, Wu N., et al. Downregulation of miR-363 increases drug resistance in cisplatin-treated HepG2 by dysregulating Mcl-1. Gene 2015; 572(1): 116–122.
Agarwal R. KSB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer 2003; 3: 502-516.
Ning Yu YXCW. Bu-Zhong-Yi-Qi Decoction, the Water Extract of Chinese Traditional Herbal Medicine, Enhances Cisplatin Cytotoxicity in A549/DDP Cells through Induction of Apoptosis and Autophagy Biomed Res Int 2017; 2017: 3692797.
Zhi-Ying Teng X-LC, Xue-Ting Cai, et al. Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity. Sci Rep 2015; 5: 15592.
J. S. Immune regulation by mesenchymal stem cells:two sides to the coin. Tissue Antigens 2007; 69(1): 1-9.
Guo J.Q. GX, Lin Z.J., et al. BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause. BMC Cell Biol 2013; 14: 1–9.
Santos N. CC, Martins N., et al. Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol 2007; 81: 495-504.
Z.H. S. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22: 7265-7279.
Fu X HY, Xie C, et al. Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage. Cytotherapy 2008; 10: 353–363.
L. K. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7: 573–584.
Zangen R RE, Sidransky D. DeltaNp63α levels correlate with clinical tumor response to cisplatin. Cell Cycle 2005; 4: 1313–1315.
Zhang R NY, Zhou Y. Increase the cisplatin cytotoxicity and cisplatin-induced DNA damage in HepG2 cells by XRCC1 abrogation related mechanisms. Toxicol Lett 2010; 192(2): 108-114.
ZH S. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22(47): 7265-7279.
Kumar S YC, Tchounwou PB. Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells. J Exp Clin Cancer Res 2014 33: 42.
Yedjou CG TP. Modulation of p53, c-fos, RARE, cyclin A, and cyclin D1 expression in human leukemia (HL-60) cells exposed to arsenic trioxide. Mol Cell Biochem 2009 331: 207-214.
Tchounwou SKPB. Molecular mechanisms of cisplatin cytotoxicity in acute promyelocytic leukemia cells. Oncotarget 2015; 6(38): 40734-40746.
Jordan P C-FM. Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci 2000; 57: 1229-1235.