Antitumor effects and mechanisms of Ganoderma extracts and spores oil

Chen,Chun; Li,Peng; Li,Ye; Yao,Guan; Xu,Jian‑Hua

doi:10.3892/ol.2016.5059

Antitumor effects and mechanisms of Ganoderma extracts and spores oil

Authors:
- Chun Chen
- Peng Li
- Ye Li
- Guan Yao
- Jian‑Hua Xu
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Affiliations: School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China, Fujian Xianzhilou Biological Science and Technology Co., Ltd, Fuzhou, Fujian 350001, P.R. China, Systems Biology Laboratory, Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
Published online on: August 29, 2016 https://doi.org/10.3892/ol.2016.5059
Pages: 3571-3578

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Abstract

Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self‑prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose‑dependent inhibitory effects on tumor cells. The half maximal inhibitory concentration (IC50) values of Ganoderma extracts on HL60, K562 and SGC‑7901 cells for 24 h were 0.44, 0.39 and 0.90 mg/ml, respectively; for Ganoderma spores oil, the IC50 values were 1.13, 2.27 and 6.29 mg/ml, respectively. In the in vivo study, the inhibitory rates of Ganoderma extracts (4 g/kg/d, intragastrically) on S180 and H22 cells were 39.1 and 44.6%, respectively, and for Ganoderma spores oil (1.2 g/kg/d, intragastrically) the inhibitory rates were 30.9 and 44.9%, respectively. Ganoderma extracts and spores oil inhibited the activities of topoisomerase I and II. Ganoderma spores oil was shown block the cell cycle at the transition between the G1 and S phases and induce a marked decrease in cyclin D1 levels in K562 cells, with no significant change in cyclin E level. These results suggest that the Ganoderma extracts and spores oil possessed antitumor effects in the in vitro and in vivo studies. The antitumor mechanisms of the extracts and spores oil were associated with inhibitory effects on topoisomerase I and II activities, and for Ganoderma spores oil, the antitumor effects may also be associated with decreased cyclin D1 levels, thus inducing G1 arrest in the cell cycle.

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1	Kuo MC, Weng CY, Ha CL and Wu MJ: Ganoderma lucidum mycelia enhance innate immunity by activating NF-kappaB. J Ethnopharmacol. 103:217–222. 2006. View Article : Google Scholar : PubMed/NCBI
2	Lai CS, Yu MS, Yuen WH, So KF, Zee SY and Chang RC: Antagonizing beta-amyloid peptide neurotoxicity of the anti-aging fungus Ganoderma lucidum. Brain Res. 1190:215–224. 2008. View Article : Google Scholar : PubMed/NCBI
3	Hong KJ, Dunn DM, Shen CL and Pence BC: Effects of Ganoderma lucidum on apoptotic and anti-inflammatory function in HT-29 human colonic carcinoma cells. Phytother Res. 18:768–770. 2004. View Article : Google Scholar : PubMed/NCBI
4	Hajjaj H, Macé C, Roberts M, Niederberger P and Fay LB: Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors. Appl Environ Microbiol. 71:3653–3658. 2005. View Article : Google Scholar : PubMed/NCBI
5	Zhang W, Tao J, Yang X, Yang Z, Zhang L, Liu H, Wu K and Wu J: Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection. Biochem Biophys Res Commun. 449:307–312. 2014. View Article : Google Scholar : PubMed/NCBI
6	Loganathan J, Jiang J, Smith A, Jedinak A, Thyagarajan-Sahu A, Sandusky GE, Nakshatri H and Sliva D: The mushroom Ganoderma lucidum suppresses breast-to-lung cancer metastasis through the inhibition of pro-invasive genes. Int J Oncol. 44:2009–2015. 2014.PubMed/NCBI
7	Mariani A, Bartoli A, Atwal M, Lee KC, Austin CA and Rodriguez R: Differential targeting of human topoisomerase II isoforms with small molecules. J Med Chem. 58:4851–4856. 2015. View Article : Google Scholar : PubMed/NCBI
8	Wu N, Wu XW, Agama K, Pommier Y, Du J, Li D, Gu LQ, Huang ZS and An LK: A novel DNA topoisomerase I inhibitor with different mechanism from camptothecin induces G2/M phase cell cycle arrest to K562 cells. Biochemistry. 49:10131–10136. 2010. View Article : Google Scholar : PubMed/NCBI
9	Li CH, Chen PY, Chang UM, Kan LS, Fang WH, Tsai KS and Lin SB: Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells. Life Sci. 77:252–265. 2005. View Article : Google Scholar : PubMed/NCBI
10	Kruczynski A, Barret JM, Van Hille B, Chansard N, Astruc J, Menon Y, Duchier C, Créancier L and Hill BT: Decreased nucleotide excision repair activity and alterations of topoisomerase II alpha are associated with the in vivo resistance of a P388 leukemia subline to F11782, a novel catalytic inhibitor of topoisomerases I and II. Clin Cancer Res. 10:3156–3168. 2004. View Article : Google Scholar : PubMed/NCBI
11	Boh B, Berovic M, Zhang J and Zhi-Bin L: Ganoderma lucidum and its pharmaceutically active compounds. Biotechnol Annu Rev. 13:265–301. 2007. View Article : Google Scholar : PubMed/NCBI
12	Zhang S, Nie S, Huang D, Li W and Xie M: Immunomodulatory effect of Ganoderma atrum polysaccharide on CT26 tumor-bearing mice. Food Chem. 136:1213–1219. 2013. View Article : Google Scholar : PubMed/NCBI
13	Hsin IL, Ou CC, Wu TC, Jan MS, Wu MF, Chiu LY, Lue KH and Ko JL: GMI, an immunomodulatory protein from Ganoderma microsporum, induces autophagy in non-small cell lung cancer cells. Autophagy. 7:873–882. 2011. View Article : Google Scholar : PubMed/NCBI
14	Zhu XL and Lin ZB: Effects of Ganoderma lucidum polysaccharides on proliferation and cytotoxicity of cytokine-induced killer cells. Acta Pharmacol Sin. 26:1130–1137. 2005. View Article : Google Scholar : PubMed/NCBI
15	Gao Y, Gao H, Chan E, Tang W, Xu A, Yang H, Huang M, Lan J, Li X, Duan W, et al: Antitumor activity and underlying mechanisms of ganopoly, the refined polysaccharides extracted from Ganoderma lucidum, in mice. Immunol Invest. 34:171–198. 2005. View Article : Google Scholar : PubMed/NCBI
16	Hofland K, Petersen BO, Falck J, Helin K, Jensen PB and Sehested M: Differential cytotoxic pathways of topoisomerase I and II anticancer agents after overexpression of the E2F-1/DP-1 transcription factor complex. Clin Cancer Res. 6:1488–1497. 2000.PubMed/NCBI
17	Peng X, Liu J, Xia J, Wang C, Li X, Deng Y, Bao N, Zhang Z and Qiu M: Lanostane triterpenoids from Ganoderma hainanense J. D. Zhao. Phytochemistry. 114:137–145. 2015. View Article : Google Scholar : PubMed/NCBI
18	Xu YN and Zhong JJ: Impacts of calcium signal transduction on the fermentation production of antitumor ganoderic acids by medicinal mushroom Ganoderma lucidum. Biotechnol Adv. 30:1301–1308. 2012. View Article : Google Scholar : PubMed/NCBI
19	Tang W, Liu JW, Zhao WM, Wei DZ and Zhong JJ: Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sciences. 80:205–211. 2006. View Article : Google Scholar : PubMed/NCBI