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Erschienen in: Journal of Natural Medicines 1/2018

30.08.2017 | Original Paper

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

verfasst von: Huilong Wen, Zhong Wu, Huidong Hu, Yixiong Wu, Gang Yang, Jiajun Lu, Guang Yang, Gang Guo, Qirong Dong

Erschienen in: Journal of Natural Medicines | Ausgabe 1/2018

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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.
Literatur
3.
Zurück zum Zitat 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):269–290CrossRefPubMed 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):269–290CrossRefPubMed
4.
Zurück zum Zitat Ríos J-L (2011) Chemical constituents and pharmacological properties of Poria cocos. Planta Med 77(07):681–691CrossRefPubMed Ríos J-L (2011) Chemical constituents and pharmacological properties of Poria cocos. Planta Med 77(07):681–691CrossRefPubMed
5.
Zurück zum Zitat Tai T, Akahori A, Shingu T (1991) Triterpenoids from Poria cocos. Phytochemistry 30(8):2796–2797CrossRef Tai T, Akahori A, Shingu T (1991) Triterpenoids from Poria cocos. Phytochemistry 30(8):2796–2797CrossRef
6.
Zurück zum Zitat 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):382–385CrossRefPubMed 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):382–385CrossRefPubMed
7.
Zurück zum Zitat 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):609–620CrossRefPubMed 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):609–620CrossRefPubMed
8.
Zurück zum Zitat 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):1877–1880CrossRefPubMed 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):1877–1880CrossRefPubMed
9.
Zurück zum Zitat 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):1153–1161CrossRefPubMed 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):1153–1161CrossRefPubMed
10.
Zurück zum Zitat 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):271–282PubMed 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):271–282PubMed
11.
Zurück zum Zitat 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):1516–1524CrossRefPubMed 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):1516–1524CrossRefPubMed
12.
Zurück zum Zitat 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):977–979CrossRef 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):977–979CrossRef
13.
Zurück zum Zitat 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):2093–2099CrossRefPubMed 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):2093–2099CrossRefPubMed
14.
Zurück zum Zitat 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):1491–1500CrossRefPubMed 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):1491–1500CrossRefPubMed
15.
Zurück zum Zitat 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):465–472PubMed 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):465–472PubMed
16.
Zurück zum Zitat 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):4240–4245CrossRefPubMedPubMedCentral 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):4240–4245CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Soldani C, Scovassi AI (2002) Poly (ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 7(4):321–328CrossRefPubMed Soldani C, Scovassi AI (2002) Poly (ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 7(4):321–328CrossRefPubMed
18.
Zurück zum Zitat 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):192CrossRef 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):192CrossRef
19.
Zurück zum Zitat 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):1782–1784CrossRefPubMed 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):1782–1784CrossRefPubMed
20.
Zurück zum Zitat Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6(2):99–104CrossRefPubMed Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6(2):99–104CrossRefPubMed
21.
Zurück zum Zitat Morgensztern D, McLeod HL (2005) PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 16(8):797–803CrossRefPubMed Morgensztern D, McLeod HL (2005) PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 16(8):797–803CrossRefPubMed
22.
Metadaten
Titel
The anti-tumor effect of pachymic acid on osteosarcoma cells by inducing PTEN and Caspase 3/7-dependent apoptosis
verfasst von
Huilong Wen
Zhong Wu
Huidong Hu
Yixiong Wu
Gang Yang
Jiajun Lu
Guang Yang
Gang Guo
Qirong Dong
Publikationsdatum
30.08.2017
Verlag
Springer Singapore
Erschienen in
Journal of Natural Medicines / Ausgabe 1/2018
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-017-1117-2

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