Dioscin-induced apoptosis of human LNCaP prostate carcinoma cells through activation of caspase-3 and modulation of Bcl-2 protein family

Jing Chen , Hui-min Li , Xue-nong Zhang , Chao-mei Xiong , Jin-lan Ruan

Current Medical Science ›› 2014, Vol. 34 ›› Issue (1) : 125 -130.

PDF
Current Medical Science ›› 2014, Vol. 34 ›› Issue (1) : 125 -130. DOI: 10.1007/s11596-014-1243-y
Article

Dioscin-induced apoptosis of human LNCaP prostate carcinoma cells through activation of caspase-3 and modulation of Bcl-2 protein family

Author information +
History +
PDF

Abstract

Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin (1, 2 and 4 μmol/L) could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.

Keywords

dioscin / LNCaP / anti-tumor / apoptosis pathway / capsase-3 / Bcl-2 protein family

Cite this article

Download citation ▾
Jing Chen, Hui-min Li, Xue-nong Zhang, Chao-mei Xiong, Jin-lan Ruan. Dioscin-induced apoptosis of human LNCaP prostate carcinoma cells through activation of caspase-3 and modulation of Bcl-2 protein family. Current Medical Science, 2014, 34(1): 125-130 DOI:10.1007/s11596-014-1243-y

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

CarterHB, CoffeyDS. The prostate: an increasing medical problem. Prostate, 1990, 16(1): 39-48

[2]

JemalA, SiegelR, WardE, et al.. Cancer statistics. CA Cancer J Clin, 2008, 58(2): 71-96

[3]

SwinnenJV, HeemersH, de SandeTV, et al.. Androgens, lipogenesis and prostate cancer. J Steroid Biochem Mol Biol, 2004, 92(4): 273-279

[4]

WigleDT, TurnerMC, GomesJ, et al.. Role of hormonal and other factors in human prostate cancer. J Toxicol Environ Health B Crit Rev, 2008, 11(3–4): 242-259

[5]

JooSS, YooYM. Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. J Pineal Res, 2009, 47(1): 8-14

[6]

ShawGL, WilsonP, CuzickJ, et al.. International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate: a meta-analysis of 1446 patients. BJU Int, 2007, 99(5): 1056-1065

[7]

OkadaH, MakTW. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer, 2004, 4(8): 592-603

[8]

TangDG, PorterAT. Target to apoptosis: a hopeful weapon for prostate cancer. Prostate, 1997, 32(4): 284-293

[9]

PorterAG, JänickeRU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ, 1999, 6(2): 99-104

[10]

LiuDZ, TianZ, YanZH, et al.. Design, synthesis and evaluation of 1,2-benzisothiazol-3-one derivatives as potent caspase-3 inhibitors. Bioorg Med Chem, 2013, 21(11): 2960-2967

[11]

GrossA. BCL-2 proteins: regulators of the mitochondrial apoptotic program. IUBMB Life, 2001, 52(3–5): 231-236

[12]

AdamsJM, CoryS. The Bcl-2 protein family: arbiters of cell survival. Science, 1998, 281(5381): 1322-1326

[13]

O’BrienMA, KirbyR. Apoptosis: a review of pro-apoptotic and anti-apoptotic pathways and dysregulation in disease. J Vet Emerg Crit Car, 2008, 18(6): 572-585

[14]

BushJA, LiG. The role of Bcl-2 family members in the progression of cutaneous melanoma. Clin Exp Metastas, 2001, 20(6): 531-539

[15]

StrasserA, CoryS, AdamsJM. Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J, 2011, 30(18): 3667-3683

[16]

PowerC, FanningN, RedmondHP. Cellular apoptosis and organ injury in sepsis: a review. Shock, 2002, 18(3): 197-211

[17]

Del PoetaG, VendittiA, Del PrincipeMI, et al.. Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood, 2003, 101(6): 2125-2131

[18]

HoJW, LeungYK, ChanCP. Herbal medicine in the treatment of cancer. Curr Med Chem Anticancer Agents, 2002, 2(2): 209-214

[19]

D’IncalciM, StewardWP, GescherAJ. Use of cancer chemopreventive phytochemicals as antineoplastic agents. Lancet Oncol, 2005, 6(11): 899-904

[20]

SunWJ, TuGZ, ZhangYM. A new steroidal saponin from Dioscorea zingiberensis Wright. Nat Prod Res, 2003, 17(4): 287-292

[21]

XuY, WangHY, JiangJY, et al.. Studies on steroidal saponins from Smilax china and their cytotoxic activities. Chin J Exp Trad Med Form (Chinese), 2011, 17(11): 92-96

[22]

WangLJ, MengQ, WangCY, et al.. Dioscin restores the activity of the anticancer agent adriamycin in multidrug- resistant human leukemia K562/adriamycin cells by down-regulating MDR1 via a mechanism involving NF-κB signaling inhibition. J Nat Prod, 2013, 76(5): 909-914

[23]

LiuCH, WangY, WuCC, et al.. Dioscin’s antiviral effect in vitro. Virus Res, 2013, 172(1-2): 9-14

[24]

LuBN, YinLH, XuLN, et al.. Application of proteomic and bioinformatic techniques for studying the hepatoprotective effect of dioscin against CCl4-induced liver damage in mice. Planta Med, 2011, 77(5): 407-415

[25]

HuMM, XuLN, YinLH, et al.. Cytotoxicity of dioscin in human gastric carcinoma cells through death receptor and mitochondrial pathways. J Appl Toxicol, 2013, 33(8): 712-722

[26]

MiQW, LantvitD, Reyes-LimE, et al.. Evaluation of the potential cancer chemotherapeutic efficacy of natural product isolates employing in vivo hollow fiber tests. J Nat Prod, 2002, 65(6): 842-850

[27]

MosmannT. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 1983, 65(1–2): 55-63

[28]

ZhouYP. The calculation of LD50 in new drugs with software SPSS. Prog Pharm Sci (Chinese), 2003, 27(5): 314-316

[29]

SheppardBC, RuttenMJ, MeichsnerGL, et al.. Effects of paclitaxel on the growth of normal, polyposis, and cancerous human colonic epithelial cells. Cancer, 1999, 85(7): 1454-1464

[30]

CaiJ, LiuMJ, WangZ, et al.. Apoptosis induced by dioscin in hela cells. Biol Pharm Bull, 2002, 25(2): 193-196

[31]

WangZ, ZhouJB, JuY, et al.. Effects of two saponins extracted from the Polygonatum Zanlanscianense Pamp on the human leukemia (HL-60) cells. Biol Pharm Bull, 2001, 24(2): 159-162

[32]

WangY, CheungYH, YangZQ, et al.. Proteomic approach to study the cytotoxicity of dioscin (saponin). Proteomics, 2006, 6(8): 2422-2432

[33]

WangZY, ChengY, WangN, et al.. Dioscin induces cancer cell apoptosis through elevated oxidative stress mediated by downregulation of peroxiredoxins. Cancer Biol Ther, 2012, 13(3): 138-147

[34]

GolbanoJM, López-AparicioP, RecioMN, et al.. Finasteride induces apoptosis via Bcl-2, Bcl-xL, Bax and caspase-3 proteins in LNCaP human prostate cancer cell line. Int J Oncol, 2008, 32(4): 919-924

[35]

AshePC, BerryMD. Apoptotic signaling cascades. Prog Neuro-psychopharmacol Biol Psychiatry, 2003, 27(2): 199-214

[36]

SarasteA, PulkkiK. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res, 2000, 45(3): 528-537

[37]

CoryS, AdamsJM. The Bcl2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer, 2002, 2(9): 647-656

[38]

KimMO, MoonDO, KangCH, et al.. Water-soluble chitosan sensitizes apoptosis in human leukemia cells via the downregulation of bcl-2 and dephosphorylation of AKT. J Food Biochem, 2013, 37(3): 270-277

AI Summary AI Mindmap
PDF

100

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/