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Journal of Natural Medicines

, Volume 72, Issue 1, pp 57–63 | Cite as

The anti-tumor effect of pachymic acid on osteosarcoma cells by inducing PTEN and Caspase 3/7-dependent apoptosis

  • Huilong Wen
  • Zhong Wu
  • Huidong Hu
  • Yixiong Wu
  • Gang Yang
  • Jiajun Lu
  • Guang Yang
  • Gang GuoEmail author
  • Qirong DongEmail author
Original Paper

Abstract

Pachymic acid (PA) is a lanostane type triterpenoid isolated from Poria cocos, which possesses an anti-tumor effect in breast cancer, prostate cancer, lung cancer, and bladder cancer cells. In this study, we investigated the effect of PA on the growth and apoptosis of human immortalized cell line (HOS) and primary osteosarcoma cells by a Cell Counting Kit-8 (CCK-8) and Annexin V and propidium iodide (PI) staining, respectively. Western blot was used to measure the expression of cleaved Caspase 3, PTEN, and AKT, as well as the AKT phosphorylation. The Caspase 3 activity was determined using the Caspase-3 Colorimetric Assay Kit. From the results, PA significantly reduced cell proliferation in a concentration- and time-dependent manner. PA also induced cell apoptosis in a dose-dependent fashion. PA treatment led to increased Caspase 3 activation and PTEN expression, as well as reduced AKT phosphorylation. Moreover, Ac-DEVD-CHO (a Caspase 3/7 inhibitor) pre-treatment or PTEN knockdown partially blocked the effects of PA on cell proliferation and apoptosis. Caspase 3/7 inhibitor had an additive effect with PTEN knockdown. Collectively, our results suggested that induction of apoptosis by PA was mediated in part by PTEN/AKT signaling and Caspase 3/7 activity. This study provides evidence that PA might be useful in the treatment of human osteosarcoma.

Keywords

Pachymic acid Osteosarcoma PTEN Caspase 3 Apoptosis 

References

  1. 1.
    Zhu H, Tang J, Tang M, Cai H (2013) Upregulation of SOX9 in osteosarcoma and its association with tumor progression and patients’ prognosis. Diagn Pathol 8:183. doi: 10.1186/1746-1596-8-183 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Jaffe N (2009) Osteosarcoma: review of the past, impact on the future. The American experience. Cancer Treat Res 152:239–262. doi: 10.1007/978-1-4419-0284-9_12 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Budihardjo I, Oliver H, Lutter M, Luo X, Wang X (1999) Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15(1):269–290CrossRefGoogle Scholar
  4. 4.
    Ríos J-L (2011) Chemical constituents and pharmacological properties of Poria cocos. Planta Med 77(07):681–691CrossRefGoogle Scholar
  5. 5.
    Tai T, Akahori A, Shingu T (1991) Triterpenoids from Poria cocos. Phytochemistry 30(8):2796–2797CrossRefGoogle Scholar
  6. 6.
    Kaminaga T, Yasukawa K, Kanno H, Tai T, Nunoura Y, Takido M (1996) Inhibitory effects of lanostane-type triterpene acids, the components of Poria cocos, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Oncology 53(5):382–385CrossRefGoogle Scholar
  7. 7.
    Ling H, Zhang Y, Ng K-Y, Chew E-H (2011) Pachymic acid impairs breast cancer cell invasion by suppressing nuclear factor-κB-dependent matrix metalloproteinase-9 expression. Breast Cancer Res Treat 126(3):609–620CrossRefGoogle Scholar
  8. 8.
    Hong R, Shen M-H, Xie X-H, Ruan S-M (2012) Inhibition of breast cancer metastasis via PITPNM3 by pachymic acid. Asian Pac J Cancer Prev 13(5):1877–1880CrossRefGoogle Scholar
  9. 9.
    Gapter L, Wang Z, Glinski J, Ng K-y (2005) Induction of apoptosis in prostate cancer cells by pachymic acid from Poria cocos. Biochem Biophys Res Commun 332(4):1153–1161CrossRefGoogle Scholar
  10. 10.
    Ling H, Jia X, Zhang Y, Gapter LA, Lim Y-s, Agarwal R, Ng K-y (2010) Pachymic acid inhibits cell growth and modulates arachidonic acid metabolism in nonsmall cell lung cancer A549 cells. Mol Carcinog 49(3):271–282PubMedPubMedCentralGoogle Scholar
  11. 11.
    Jeong JW, Lee WS, Go S-i, Nagappan A, Baek JY, Lee JD, Lee SJ, Park C, Kim GY, Kim HJ (2015) Pachymic acid induces apoptosis of EJ bladder cancer cells by DR5 up-regulation, ROS generation, modulation of Bcl-2 and IAP family members. Phytother Res 29(10):1516–1524CrossRefGoogle Scholar
  12. 12.
    Cuéllar MJ, Giner RM, Recio MC, Just MJ, Máñez S, Ríos JL (1996) Two fungal lanostane derivatives as phospholipase A2 inhibitors. J Nat Prod 59(10):977–979CrossRefGoogle Scholar
  13. 13.
    Park D-W, Kim J-R, Kim S-Y, Sonn J-K, Bang O-S, Kang S-S, Kim J-H, Baek S-H (2003) Akt as a mediator of secretory phospholipase A2 receptor-involved inducible nitric oxide synthase expression. J Immunol 170(4):2093–2099CrossRefGoogle Scholar
  14. 14.
    Díaz-Montero CM, Wygant JN, Mcintyre BW (2006) PI3-K/Akt-mediated anoikis resistance of human osteosarcoma cells requires Src activation. Eur J Cancer 42(10):1491–1500CrossRefGoogle Scholar
  15. 15.
    Miwa S, Sugimoto N, Shirai T, Hayashi K, Nishida H, Ohnari I, Takeuchi A, Yachie A, Tsuchiya H (2011) Caffeine activates tumor suppressor PTEN in sarcoma cells. Int J Oncol 39(2):465–472PubMedPubMedCentralGoogle Scholar
  16. 16.
    Cantley LC, Neel BG (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA 96(8):4240–4245CrossRefGoogle Scholar
  17. 17.
    Soldani C, Scovassi AI (2002) Poly (ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 7(4):321–328CrossRefGoogle Scholar
  18. 18.
    Steelman LS, Chappell WH, Abrams SL, Kempf CR, Long J, Laidler P, Mijatovic S, Maksimovic-Ivanic D, Stivala F, Mazzarino MC, Donia M (2011) Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY) 3(3):192CrossRefGoogle Scholar
  19. 19.
    Yang G, Sun X, Wang R (2004) Hydrogen sulfide-induced apoptosis of human aorta smooth muscle cells via the activation of mitogen-activated protein kinases and caspase-3. FASEB J 18(14):1782–1784CrossRefGoogle Scholar
  20. 20.
    Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6(2):99–104CrossRefGoogle Scholar
  21. 21.
    Morgensztern D, McLeod HL (2005) PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 16(8):797–803CrossRefGoogle Scholar
  22. 22.
    Simpson L, Parsons R (2001) PTEN: life as a tumor suppressor. Exp Cell Res 264(1):29–41CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK 2017

Authors and Affiliations

  • Huilong Wen
    • 1
    • 3
  • Zhong Wu
    • 2
  • Huidong Hu
    • 1
  • Yixiong Wu
    • 1
  • Gang Yang
    • 1
  • Jiajun Lu
    • 1
  • Guang Yang
    • 3
  • Gang Guo
    • 4
    Email author
  • Qirong Dong
    • 3
    Email author
  1. 1.Department of OrthopedicsChangzhou Tumor Hospital Affiliated to Suzhou UniversityChangzhouPeople’s Republic of China
  2. 2.Department of Orthopedics, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiPeople’s Republic of China
  3. 3.Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
  4. 4.Department of Emergency, Tongji HospitalTongji University School of MedicineShanghaiPeople’s Republic of China

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