International Journal of Applied Science and Engineering
Published by Chaoyang University of Technology

Badrinathan Sridharan1, Shu-Yu Yang2, Jen-Ying Li2, Meng-Jen Lee1*

1Department of Applied Chemistry, Chaoyang University of Technology, 168, Jifeng E. Rd., Wufeng District, Taichung City 413310, Taiwan

2Department of Chinese Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Fengxing Rd, Tanzi District, Taichung, Taiwan, ROC

 

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ABSTRACT

Traditional medicine and compounds identified from the medicinal plant extract and nutraceuticals were known to show significant beneficial effects on human health. Cynanchum paniculatum is a medicinal herb successful in treatment of many microbial infectious and metabolic disorders such as cancer. Management of tumors are still a big challenge for oncologists because there are several complex mechanisms in the cancerous cells, that influence the host system to support the tumor microenvironment. One of the well-established properties of cancerous cell is its metastasizing ability, which makes tumor development in other organs and higher recurrence rate. Cancer cells attains the metastatic property by inducing a specific pathway called epithelial to mesenchymal transition (EMT). It was observed that the inhibition of cell migration was effective in both CP extract and conditioned medium supplemented cells compared to their respective controls. We found that, in MCF-7 cells, conditioned medium showed better activity than direct CP extract treatment. This shows that CP extract interferes with cell migration and pertaining intracellular signals. We presume that the major reason behind this would be the effect of CP on modulation in exosomal pathway and their communication through secreted biomolecules. In conclusion, EMT signaling plays a crucial role in tumor metastasis and CP extract played a significant role in inhibition of cell migration through intra/extracellular signaling of cancer cells. This can be an important finding for future studies on the role of CP constituents against cancer metastasis and recurrence.


Keywords: Cynanchum paniculatum, Epithelial to mesenchymal transition, Cell migration, Breast cancer, Triple-negative cells.


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REFERENCES

  1. Abu Bakar, M. F., Saifudin, A., Cao, P., Esa, N. M. 2021. Herbal Medicine for Prevention and Therapy in Breast Cancer. Evidence-Based Complementary and Alternative Medicine, 9760586.

  2. Amaral, R., dos Santos, S. A., Andrade, L. N., Severino, P., Carvalho, A. A. 2019. Natural products as treatment against cancer: a historical and current vision. Clinical Oncology, 4, 1562.

  3. Chen, B., Ning, M., Yang, G. 2012. Effect of paeonol on antioxidant and immune regulatory activity in hepatocellular carcinoma rats. Molecules, 17, 4672–4683.

  4. Chen, J.-X., Cheng, C.-S., Chen, J., Lv, L.-L., Chen, Z.-J., Chen, C., Zheng, L, 2020. Cynanchum paniculatum and its major active constituents for inflammatory-related diseases: a review of traditional use, multiple pathway modulations, and clinical applications. Evidence-Based Complementary and Alternative Medicine, 7259686.

  5. Cheng, C.-S., Chen, J.-X., Tang, J., Geng, Y.-W., Zheng, L., Lv, L.-L., Chen, L. Y., Chen, Z. 2020. Paeonol inhibits pancreatic cancer cell migration and invasion through the inhibition of TGF-β1/smad signaling and epithelial-mesenchymal-transition. Cancer Management and Research, 12, 641–651.

  6. Cho, J. A., Park, H., Lim, E. H., Lee, K. W. 2012. Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. International Journal of Oncology, 40, 130–138.

  7. Dai, X., Cheng, H., Bai, Z., Li, J. 2017. Breast cancer cell line classification and its relevance with breast tumor subtyping. Journal of Cancer, 8, 3131–3141.

  8. Deryugina, E. I., Quigley, J. P. 2012. Cell surface remodeling by plasmin: a new function for an old enzyme. Journal of Biomedicine and Biotechnology, 564259.

  9. Duffy, M. J., McGowan, P. M., Harbeck, N., Thomssen, C., Schmitt, M. 2014. uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Research, 16, 1–10.

  10. Efferth, T., Kuete, V. 2010. Cameroonian medicinal plants: pharmacology and derived natural products. Frontiers in Pharmacology, 1: 123.

  11. Ethier, S. P., Mahacek, M. L., Gullick, W. J., Frank, T. S., Weber, B. L. 1993. Differential isolation of normal luminal mammary epithelial cells and breast cancer cells from primary and metastatic sites using selective media. Cancer research, 53, 627–635.

  12. Fedele, M., Cerchia, L., Chiappetta, G. 2017. The epithelial-to-mesenchymal transition in breast cancer: focus on basal-like carcinomas. Cancers, 9, 134.

  13. Felipe Lima, J., Nofech-Mozes, S., Bayani, J., Bartlett, J. 2016. EMT in breast carcinoma-a review. Journal of Clinical Medicine, 5, 65.

  14. Ferraiuolo, R.-M., Wagner, K.-U. 2019. Regulation and new treatment strategies in breast cancer. Journal of Life Sciences (Westlake Village, Calif.), 1, 23.

  15. Fu, J., Yu, L., Luo, J., Huo, R., Zhu, B. 2018. Paeonol induces the apoptosis of the SGC‑7901 gastric cancer cell line by downregulating ERBB2 and inhibiting the NF‑κB signaling pathway. International Journal of Molecular Medicine, 42, 1473–1483.

  16. Fu, M., Wang, D., Hu, X., Guo, M. 2015. Chemical constituents from Cynanchum paniculatum. Journal of Chinese Medicinal Materials, 38, 97–100.

  17. Giordano, C., La Camera, G., Gelsomino, L., Barone, I., Bonofiglio, D., Andò, S., Catalano, S. 2020. The biology of exosomes in breast cancer progression: Dissemination, immune evasion and metastatic colonization. Cancers, 12, 2179.

  18. Gonzalez, D. M., Medici, D. 2014. Signaling mechanisms of the epithelial-mesenchymal transition. Science Signaling, 7, 8.

  19. Jeibouei, S., Akbari, M. E., Kalbasi, A., Aref, A. R., Ajoudanian, M., Rezvani, A., Zali, H. 2019. Personalized medicine in breast cancer: pharmacogenomics approaches. Pharmacogenomics and Personalized Medicine, 12, 59.

  20. Kala, C. P., Dhyani, P. P., & Sajwan, B. S. 2006. Developing the medicinal plants sector in northern India: challenges and opportunities. Journal of Ethnobiology and Ethnomedicine, 2, 1–15.

  21. Kast, K., Link, T., Friedrich, K., Petzold, A., Niedostatek, A., Schoffer, O., Werner, C., Klug, S.J., Werner, A., Gatzweiler, A. 2015. Impact of breast cancer subtypes and patterns of metastasis on outcome. Breast Cancer Research and Treatment, 150, 621–629.

  22. Kim, C.S., Oh, J.Y., Choi, S.U., Lee, K.R. 2013. Chemical constituents from the roots of Cynanchum paniculatum and their cytotoxic activity. Carbohydrate Research, 381, 1–5.

  23. Kong, D., Chen, L., Huang, W., Zhang, Z., Wang, L., Zhang, F., Zheng, S. 2020. Combined therapy with ligustrazine and paeonol mitigates hepatic fibrosis through destroying mitochondrial integrity of stellate cell. American Journal of Translational Research, 12, 1255.

  24. Kong, D., Zhang, F., Wei, D., Zhu, X., Zhang, X., Chen, L., Lu, Y., Zheng, S. 2013. Paeonol inhibits hepatic fibrogenesis via disrupting nuclear factor-κB pathway in activated stellate cells: In vivo and in vitro studies. Journal of Gastroenterology and Hepatology, 28, 1223–1233.

  25. Lamartiniere, C. A. 2000. Protection against breast cancer with genistein: a component of soy. The American Journal of Clinical Nutrition, 71, 1705S–1707S.
  26. Lamouille, S., Xu, J., Derynck, R. 2014. Molecular mechanisms of epithelial–mesenchymal transition. Nature Reviews Molecular cell biology, 15, 178–196.

  27. Laskar, Y.B., Lourembam, R.M., Mazumder, P.B. 2020. Herbal Remedies for Breast Cancer Prevention and Treatment, Medicinal Plants-Use in Prevention and Treatment of Diseases. IntechOpen.

  28. Li, M., Tan, S.Y., Zhang, J., You, H.X. 2013. Effects of paeonol on intracellular calcium concentration and expression of RUNX3 in LoVo human colon cancer cells. Molecular Medicine Reports, 7, 1425–1430.

  29. Li, N., Fan, L.-L., Sun, G.-P., Wan, X.-A., Wang, Z.-G., Wu, Q., Wang, H. 2010. Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo. World Journal of Gastroenterology, 16, 4483.

  30. Li, T. S., 2006. Taiwanese native medicinal plants: phytopharmacology and therapeutic values. Routledge: Taylor & Franccis group

  31. Li, Y.-j., Bao, J.-X., Xu, J.-w., Murad, F., Bian, K. 2010. Vascular dilation by paeonol-a mechanism study. Vascular Pharmacology, 53, 169–176.

  32. Liao, W.-Y., Tsai, T.-H., Ho, T.-Y., Lin, Y.-W., Cheng, C.-Y., Hsieh, C.-L. 2016.
    Neuroprotective effect of paeonol mediates anti-inflammation via suppressing toll-like receptor 2 and toll-like receptor 4 signaling pathways in cerebral ischemia-reperfusion injured rats. Evidence-Based Complementary and Alternative Medicine, 3704647.

  33. Liu, C.-M., Yang, H.-X., Ma, J.-Q., Yang, W., Feng, Z.-J., Sun, J.-M., Cheng, C., Li, J., Jiang, H. 2018. Role of AMPK pathway in lead-induced endoplasmic reticulum stress in kidney and in paeonol-induced protection in mice. Food and Chemical Toxicology, 122, 87–94.

  34. Liu, M.-H., Lin, A.-H., Lee, H.-F., Ko, H.-K., Lee, T.-S., Kou, Y.R. 2014. Paeonol attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling. Mediators of inflammation, 651890.

  35. Lu, L., Qin, Y., Chen, C., Guo, X. 2018. Beneficial effects exerted by paeonol in the management of atherosclerosis. Oxidative medicine and cellular longevity, 1098617.

  36. Luga, V., Zhang, L., Viloria-Petit, A.M., Ogunjimi, A.A., Inanlou, M.R., Chiu, E., Buchanan, M., Hosein, A.N., Basik, M., Wrana, J.L. 2012. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell, 151, 1542–1556.

  37. Lyu, Z.K., Li, C.L., Jin, Y., Liu, Y.Z., Zhang, X., Zhang, F., Ning, L.N., Liang, E.S., Ma, M., Gao, W. 2017. Paeonol exerts potential activities to inhibit the growth, migration and invasion of human gastric cancer BGC823 cells via downregulating MMP‑2 and MMP‑9. Molecular Medicine Reports, 16, 7513–7519.

  38. Malhotra, G.K., Zhao, X., Band, H., Band, V. 2010. Histological, molecular and functional subtypes of breast cancers. Cancer Biology & Therapy, 10, 955–960.

  39. Mani, S.A., Guo, W., Liao, M.-J., Eaton, E.N., Ayyanan, A., Zhou, A.Y., Brooks, M., Reinhard, F., Zhang, C.C., Shipitsin, M. 2008. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133, 704–715.

  40. Massagué, J. 2008. TGFβ in cancer. Cell, 134, 215–230.

  41. Menck, K., Klemm, F., Gross, J.C., Pukrop, T., Wenzel, D., Binder, C. 2013. Induction and transport of Wnt 5a during macrophage-induced malignant invasion is mediated by two types of extracellular vesicles. Oncotarget, 4, 2057.

  42. Miettinen, P.J., Ebner, R., Lopez, A.R., Derynck, R. 1994. TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. The Journal of Cell Biology, 127, 2021–2036.

  43. Mittal, V. 2018. Epithelial mesenchymal transition in tumor metastasis. Annual Review of Pathology: Mechanisms of Disease, 13, 395–412.

  44. Nasri, H., Baradaran, A., Shirzad, H., Rafieian-Kopaei, M. 2014. New concepts in nutraceuticals as alternative for pharmaceuticals. International Journal of Preventive Medicine, 5, 1487.

  45. Ogba, N., Manning, N.G., Bliesner, B.S., Ambler, S.K., Haughian, J.M., Pinto, M.P., Jedlicka, P., Joensuu, K., Heikkilä, P., Horwitz, K.B. 2014. Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells. Breast Cancer Research, 16, 1–14.

  46. Orlando, L., Schiavone, P., Fedele, P., Calvani, N., Nacci, A., Rizzo, P., Marino, A., D'Amico, M., Sponziello, F., Mazzoni, E. 2010. Molecularly targeted endocrine therapies for breast cancer. Cancer Treatment Reviews, 36, S67–S71.

  47. Pawar, A., Rajalakshmi, S., Mehta, P., Shaikh, K., Bothiraja, C. 2016. Strategies for formulation development of andrographolide. RSC Advances, 6, 69282–69300.

  48. Saahene, R.O., Wang, J., Wang, M.-L., Agbo, E., Pang, D. 2018. The antitumor mechanism of paeonol on CXCL4/CXCR3-B signals in breast cancer through induction of tumor cell apoptosis. Cancer Biotherapy & Radiopharmaceuticals, 33, 233–240.

  49. Samavat, H., Kurzer, M.S. 2015. Estrogen metabolism and breast cancer. Cancer letters, 356, 231–243.

  50. Sun, F., Cai, M., Lou, F. 1993. Analgesic effect and gastro-intestinal motility inhibitory action of 3-hydroxy-4-methoxy-acetophenone from Cynanchum paniculatum (Bunge) Kitagawa. China Journal of Chinese Materia Medica, 18, 362–363,

  51. Sun, G.-P., Wan, X., Xu, S.-P., Wang, H., Liu, S.-H., Wang, Z.-G. 2008. Antiproliferation and apoptosis induction of paeonol in human esophageal cancer cell lines. Diseases of the Esophagus, 21, 723–729.

  52. Sun, X., Wang, P., Yao, L.-P., Wang, W., Gao, Y.-M., Zhang, J., Fu, Y.-J. 2018. Paeonol alleviated acute alcohol-induced liver injury via SIRT1/Nrf2/NF-κB signaling pathway. Environmental Toxicology and Pharmacology, 60, 110–117.

  53. Tang, Y., Huang, W., Song, Q., Zheng, X., He, R., Liu, J. 2018. Paeonol ameliorates ovalbumin-induced asthma through the inhibition of TLR4/NF-κB and MAPK signaling. Evidence-Based Complementary and Alternative Medicine, 3063145.

  54. Vella, L. J. 2014. The emerging role of exosomes in epithelial–mesenchymal-transition in cancer. Frontiers in Oncology, 4, 361.

  55. Wan, X.-A., Sun, G.-P., Wang, H., Xu, S.-P., Wang, Z.-G., Liu, S.-H. 2008. Synergistic effect of paeonol and cisplatin on oesophageal cancer cell lines. Digestive and Liver Disease, 40, 531–539.

  56. Wang, J., Wu, G., Chu, H., Wu, Z., Sun, J. 2020. Paeonol derivatives and pharmacological activities: A review of recent progress. Mini reviews in medicinal chemistry, 20, 466–482.

  57. Wang, S.-C., Bao, X.-F., Fang, J.-N. 2002. Structural features of a neutral heteropolysaccharide CPB-4 from Cynanchum paniculatum. China Journal of Chinese Materia Medica, 27, 128–130.

  58. Weon, J.B., Kim, C.Y., Yang, H.J., Ma, C.J. 2012. Neuroprotective compounds isolated from Cynanchum paniculatum. Archives of Pharmacal Research, 35, 617–621.

  59. Weon, J.B., Lee, B., Yun, B.-R., Lee, J., Ma, C.J. 2014. Neuroprotective effects of 4, 5-dimethoxypyrocatechol isolated from Cynanchum paniculatum on HT22 cells. Pharmacognosy Magazine, 10, 161.

  60. Wu, J., Xu, L., Sun, C., Zhang, B., Li, J., Sun, J., Zhang, Y., Sun, D. 2017. Paeonol alleviates epirubicin-induced renal injury in mice by regulating Nrf2 and NF-κB pathways. European Journal of Pharmacology, 795, 84–93.

  61. Wu, M., Yu, Z., Li, X., Zhang, X., Wang, S., Yang, S., Hu, L., Liu, L. 2021. Paeonol for the Treatment of Atherosclerotic Cardiovascular Disease: A Pharmacological and Mechanistic Overview. Frontiers in Cardiovascular Medicine, 8, 690116.

  62. Wu, S., Liu, L., Yang, S., Kuang, G., Yin, X., Wang, Y., Xu, F., Xiong, L., Zhang, M., Wan, J. 2019. Paeonol alleviates CCl4-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling. Immunopharmacology and Immunotoxicology, 41, 438–445.

  63. Xie, B., Liu, N., Zhao, F. 2005. In vitro experimental study on the effect of Cynanchum paniculatum extract against hepatitis B virus. China Tropical Medicine, 5, 196–197.

  64. Xiong, Y., Li, B., Huang, D., He, Q., Yu, X., 2018. Anti-Deinagkistrodon acutus venom properties of ethanolic root extract from Cynanchum paniculatum (Bunge) kitag and its GC-MS analysis. Journal of Ethnopharmacology, 225, 189–197.

  65. Xu, Y., Zhu, J.-y., Lei, Z.-m., Wan, L.-j., Zhu, X.-w., Ye, F., Tong, Y.-y. 2017. Anti-proliferative effects of paeonol on human prostate cancer cell lines DU145 and PC-3. Journal of Physiology and Biochemistry, 73, 157–165.

  66. Yang, S.-Y., Li, J.Y., Huang, G.-J., Sridharan, B., Wang, J.-S., Chang, K.-M., Lee, M.-J. 2021. Effects of Water Extract of Cynanchum paniculatum (Bge.) Kitag. on Different Breast Cancer Cell Lines. Evidence-Based Complementary and Alternative Medicine, 6665949.

  67. Ye, X., Brabletz, T., Kang, Y., Longmore, G.D., Nieto, M.A., Stanger, B.Z., Yang, J., Weinberg, R.A. 2017. Upholding a role for EMT in breast cancer metastasis. Nature, 547, E1–E3.

  68. Yin, J., Wu, N., Zeng, F., Cheng, C., Kang, K., Yang, H. 2013. Paeonol induces apoptosis in human ovarian cancer cells. Acta Histochemica, 115, 835–839.

  69. Yuan, H., Ma, Q., Ye, L., Piao, G. 2016. The traditional medicine and modern medicine from natural products. Molecules, 21, 559.

  70. Zhang, J.-Y., Shang, J., Huo, T.-M., Zhang, B., Chen, G., Zeng, Z.-Y., Li, S.-K. 2017. Local application of paeonol prevents early restenosis: a study with a rabbit vein graft model. Journal of Surgical Research, 212, 278–287.

  71. Zhang, L., Ma, C., Gu, R., Zhang, M., Wang, X., Yang, L., Liu, Y., Zhou, Y., He, S., Zhu, D. 2018. Paeonol regulates hypoxia-induced proliferation of pulmonary artery smooth muscle cells via EKR 1/2 signalling. European Journal of Pharmacology, 834, 257–265.

  72. Zhou, H.M., Sun, Q.X., Cheng, Y. 2017. Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor. Experimental and Therapeutic Medicine, 14, 3213–3220.

  73. Zhou, W., Chen, Z., Sun, X., Zhong, N., Liu, Z. 2021. Application of Traditional Chinese Medicine and Systems Pharmacology in Drug Prevention and Treatment against COVID-19. The American Journal of Chinese Medicine, 49, 1045–1061.

  74. Zhou, X., Xia, W., Zhang, Y., Ma, J., Zhou, H., Dong, L., Fu, X. 2020. Cynanchum paniculatum (Bunge) Kitag. ex H. Hara: a review of its ethnopharmacology, phytochemistry and pharmacology. Journal of Ethnopharmacology, 260, 112994.

  75. Zong, S.-Y., Pu, Y.-Q., Xu, B.-L., Zhang, T., Wang, B. 2017. Study on the physicochemical properties and anti-inflammatory effects of paeonol in rats with TNBS-induced ulcerative colitis. International Immunopharmacology, 42, 32–38.

  76. Zubor, P., Hatok, J., Moricova, P., Kajo, K., Kapustova, I., Mendelova, A., Racay, P., Danko, J. 2015. Gene expression abnormalities in histologically normal breast epithelium from patients with luminal type of breast cancer. Molecular Biology Reports, 42, 977–988.

  77. Zyad, A., Leouifoudi, I., Tilaoui, M., Mouse, H.A., Khouchani, M., Jaafari, A. 2018. Natural products as cytotoxic agents in chemotherapy against cancer. Cytotoxicity, 1st edn. IntechOpen, Croatia: 65–88.


ARTICLE INFORMATION

Received: 2021-09-26
Revised: 2022-01-06
Accepted: 2022-01-12
Available Online: 2022-03-01


Cite this article:

Sridharan, B., Shu-Yu Yang, Jen-Ying Li, Meng-Jen Lee. 2022. Effect of Cynanchum paniculatum (Bge.) Kitag. on various diseases: an overview of current research progress. International Journal of Applied Science and Engineering, 19, 2021414. https://doi.org/10.6703/IJASE.202203_19(1).010

  Copyright The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are cited.

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