Ginsenoside Rg3 induces apoptosis in human multiple myeloma cells via the activation of Bcl-2-associated X protein

Luo,Yun; Zhang,Ping; Zeng,Han‑Qing; Lou,Shi‑Feng; Wang,Dao‑Xin

doi:10.3892/mmr.2015.3802

Ginsenoside Rg3 induces apoptosis in human multiple myeloma cells via the activation of Bcl-2-associated X protein

Authors:
- Yun Luo
- Ping Zhang
- Han‑Qing Zeng
- Shi‑Feng Lou
- Dao‑Xin Wang
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Affiliations: Department of Hematology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 404000, P.R. China
Published online on: May 19, 2015 https://doi.org/10.3892/mmr.2015.3802
Pages: 3557-3562

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Abstract

Ginsenoside Rg3 is one of the main constituents isolated from Panax ginseng, and exhibits cytotoxic effects against cancer cells. The present study aimed to investigate the effects of ginsenoside Rg3 on human multiple myeloma cells, and determine the underlying molecular mechanisms. The cells were exposed to ginsenoside Rg3 at various concentrations (0‑80 µM) for 48 h. A subsequent cell proliferation assay demonstrated that treatment with ginsenoside Rg3 resulted in a dose‑dependent inhibition of the proliferation of U266 and RPMI8226 cells. Furthermore, exposure to ginsenoside Rg3 led to a marked increase in the rate of apoptosis in the U266 cells, coupled with increased caspase‑3 activity. The ginsenoside Rg3‑treated cells also exhibited an elevation in the expression of B‑cell lymphoma 2‑associated X protein (Bax), a pro‑apoptotic protein. Notably, knockdown of Bax protected the U266 cells from Rg3‑induced apoptosis. Overall, these findings suggested that ginsenoside Rg3 induced apoptosis in multiple myeloma cells, at least partially, through upregulation of the expression of Bax.

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1	Mahindra A, Laubach J, Raje N, Munshi N, Richardson PG and Anderson K: Latest advances and current challenges in the treatment of multiple myeloma. Nat Rev Clin Oncol. 9:135–143. 2012. View Article : Google Scholar : PubMed/NCBI
2	Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B and Bao JK: Programmed cell death pathways in cancer: A review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 45:487–498. 2012. View Article : Google Scholar : PubMed/NCBI
3	Danial NN and Korsmeyer SJ: Cell death: Critical control points. Cell. 116:205–219. 2004. View Article : Google Scholar : PubMed/NCBI
4	Kale J, Liu Q, Leber B and Andrews DW: Shedding light on apoptosis at subcellular membranes. Cell. 151:1179–1184. 2012. View Article : Google Scholar : PubMed/NCBI
5	Oancea M, Mani A, Hussein MA and Almasan A: Apoptosis of multiple myeloma. Int J Hematol. 80:224–231. 2004. View Article : Google Scholar : PubMed/NCBI
6	Kang KA, Kim HS, Kim DH and Hyun JW: The role of a ginseng saponin metabolite as a DNA methyltransferase inhibitor in colorectal cancer cells. Int J Oncol. 43:228–236. 2013.PubMed/NCBI
7	Ma SW, Benzie IF, Chu TT, Fok BS, Tomlinson B and Critchley LA: Effect of Panax ginseng supplementation on biomarkers of glucose tolerance, antioxidant status and oxidative stress in type 2 diabetic subjects: Results of a placebo-controlled human intervention trial. Diabetes Obes Metab. 10:1125–1127. 2008. View Article : Google Scholar : PubMed/NCBI
8	Kim SM, Lee SY, Yuk DY, Moon DC, Choi SS, Kim Y, Han SB, Oh KW and Hong JT: Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Arch Pharm Res. 32:755–765. 2009. View Article : Google Scholar : PubMed/NCBI
9	Kim SM, Lee SY, Cho JS, Son SM, Choi SS, Yun YP, Yoo HS, Yoon do Y, Oh KW, Han SB and Hong JT: Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB. Eur J Pharmacol. 63:1–9. 2010. View Article : Google Scholar
10	Keum YS, Han SS, Chun KS, Park KK, Park JH, Lee SK and Surh YJ: Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat Res. 523–524:75–85. 2003. View Article : Google Scholar
11	Yu Y, Zhang C, Liu L and Li X: Hepatic arterial administration of ginsenoside Rg3 and transcatheter arterial embolization for the treatment of VX2 liver carcinomas. Exp Ther Med. 5:761–766. 2013.PubMed/NCBI
12	Yuan HD, Quan HY, Zhang Y, Kim SH and Chung SH: 20(S)-Ginsenoside Rg3-induced apoptosis in HT-29 colon cancer cells is associated with AMPK signaling pathway. Mol Med Rep. 3:825–831. 2010.
13	Sethi G, Shanmugam MK, Ramachandran L, Kumar AP and Tergaonkar V: Multifaceted link between cancer and inflammation. Biosci Rep. 32:1–15. 2012. View Article : Google Scholar
14	Jiang JW, Chen XM, Chen XH and Zheng SS: Ginsenoside Rg3 inhibit hepatocellular carcinoma growth via intrinsic apoptotic pathway. World J Gastroenterol. 17:3605–3613. 2011. View Article : Google Scholar : PubMed/NCBI
15	Kim B and Kim SH, Jeong SJ, Sohn EJ, Jung JH, Lee MH and Kim SH: Brazilin induces apoptosis and G2/M arrest via inactivation of histone deacetylase in multiple myeloma U266 cells. J Agric Food Chem. 60:9882–9889. 2012. View Article : Google Scholar : PubMed/NCBI
16	Brunelle JK and Letai A: Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 122:437–441. 2009. View Article : Google Scholar : PubMed/NCBI
17	Park HM, Kim SJ, Kim JS and Kang HS: Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways. Food Chem Toxicol. 50:2736–2741. 2012. View Article : Google Scholar : PubMed/NCBI