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Investigational New Drugs

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28.10.2017 | REVIEW

Ganoderic acid, lanostanoid triterpene: a key player in apoptosis

verfasst von: Balraj Singh Gill, Navgeet, Richa Mehra, Vicky Kumar, Sanjeev Kumar

Erschienen in: Investigational New Drugs | Ausgabe 1/2018

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Summary

Cancer is a multifactorial disease, causing behavioral and metabolic alterations, leading to uncontrolled cell proliferation with collateral weakening of immune system. Crucial balance between cell proliferation and cell death determines the fate of a cell, which might progress towards survival or apoptosis. Apoptosis is a complex, programmed, and highly regulated process causing dramatic morphological and biochemical perturbations in the cellular machinery. Ganoderma lucidum is a basidiomycetes, polypore mushroom known for its pharmacological properties in cancer. The major bioconstituents in G. lucidum are terpenoids, polysaccharides, and proteins that target cancer-signaling factors like plasma membrane receptors proteins and adapter molecules. Of all constituents, the major terpenoid, i.e. Ganoderic acid is reported to interact with membrane receptors mainly, receptor tyrosine kinase (RTKs). Ganoderic acid interacts and modulates the signaling network in IR, IGFR-1, IGFR-2, VEGFR-1, VEFGR-2, and EGFR in cancer signaling pathways. It primarily targets NF-κB, RAS-MAPK, PI3K/Akt/mTOR, and cell cycle resulting in apoptosis. This review highlights the role of ganoderic acid in apoptosis and modulations of various signaling proteins in cancer.

Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30CrossRefPubMed

Negi A, Gill B, Anand S (2014) Tilling: versatile reverse genetic tool. PharmaTutor 2(1):26–32

Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279(5349):377–380CrossRefPubMed

Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years⊥. J Nat Prod 70(3):461–477CrossRefPubMed

Gill BS, Navgeet, Kumar S (2017) Ganoderma lucidum targeting lung cancer signaling: a review. Tumor Biol 39(6):1010428317707437CrossRef

Kerr J (1965) A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. J Pathol Bacteriol 90(2):419–435CrossRefPubMed

Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239CrossRefPubMedPubMedCentral

Cotter TG (2009) Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer 9(7):501–507CrossRefPubMed

Gill BS, Alex JM, Navgeet, Kumar S (2016) Missing link between microRNA and prostate cancer. Tumor Biol 37(5):5683–5704CrossRef

10.

Schulze-Osthoff K, Walczak H, Dröge W, Krammer PH (1994) Cell nucleus and DNA fragmentation are not required for apoptosis. J Cell Biol 127(1):15–20CrossRefPubMed

11.

Rao L, Perez D, White E (1996) Lamin proteolysis facilitates nuclear events during apoptosis. J Cell Biol 135(6):1441–1455CrossRefPubMed

12.

Croft DR, Coleman ML, Li S, Robertson D, Sullivan T, Stewart CL, Olson MF (2005) Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration. J Cell Biol 168(2):245–255CrossRefPubMedPubMedCentral

13.

Rosenblatt J, Raff MC, Cramer LP (2001) An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin-and myosin-dependent mechanism. Curr Biol 11(23):1847–1857CrossRefPubMed

14.

Anand SS, Gill BS (2015) Breakthroughs in epigenetics. PharmaTutor 3(7):16–24

15.

Napirei M, Karsunky H, Zevnik B, Stephan H, Möröy T (2000) Features of systemic lupus erythematosus in Dnase1-deficient mice. Nature Genet 25(2):177–181CrossRefPubMed

16.

Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391(6662):43–50CrossRefPubMed

17.

Ramirez IB-R, Lowe M (2009) Golgins and GRASPs: holding the Golgi together. Semin Cell Dev Biol 20(7):770–779

18.

Ricci J-E, Muñoz-Pinedo C, Fitzgerald P, Bailly-Maitre B, Perkins GA, Yadava N, Scheffler IE, Ellisman MH, Green DR (2004) Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell 117(6):773–786CrossRefPubMed

19.

Lüthi A, Martin S (2007) The CASBAH: a searchable database of caspase substrates. Cell Death Differ 14(4):641–650CrossRefPubMed

20.

Bellone M, Iezzi G, Rovere P, Galati G, Ronchetti A, Protti MP, Davoust J, Rugarli C, Manfredi AA (1997) Processing of engulfed apoptotic bodies yields T cell epitopes. J Immunol 159(11):5391–5399PubMed

21.

Moss DK, Betin VM, Malesinski SD, Lane JD (2006) A novel role for microtubules in apoptotic chromatin dynamics and cellular fragmentation. J Cell Sci 119(11):2362–2374CrossRefPubMedPubMedCentral

22.

Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392(6671):86–89CrossRefPubMed

23.

Gill BS, Kumar S (2016) Triterpenes in cancer: significance and their influence. Mol Biol Rep 43(9):881–896CrossRefPubMed

24.

Gill BS, Kumar S (2016) Ganoderic acid a targeting β-catenin in Wnt signaling pathway: in silico and in vitro study. Interdiscip Sci Comput Life Sci 1–11. https://doi.org/10.1007/s12539-016-0182-7

25.

Tavakoli J, Miar S, Zadehzare MM, Akbari H (2012) Evaluation of effectiveness of herbal medication in cancer care: a review study. Iran J Cancer Prev 5(3):144–156PubMedPubMedCentral

26.

Moncalvo J (2000) Systematics of Ganoderma 2. In: Flood J, Bridge PD, Holderness M (eds) Ganoderma diseases of perennial crops. CBAI Publishing, U.S.A., p 23CrossRef

27.

Bhosle S, Ranadive K, Bapat G, Garad S, Deshpande G, Vaidya J (2010) Taxonomy and diversity of Ganoderma from the western parts of Maharashtra (India). Mycosphere 1(3):249–262

28.

Nasir N (2005) Diseases caused by Ganoderma spp. on perennial crops in Pakistan. Mycopathologia 159(1):119–121CrossRefPubMed

29.

Gill BS, Sharma P, Kumar S (2016) Chemical composition and Antiproliferative, antioxidant, and Proapoptotic effects of fruiting body extracts of the Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Agaricomycetes), from India. Int J Med Mushrooms 18(7):599–607CrossRef

30.

Shiao MS (2003) Natural products of the medicinal fungus Ganoderma lucidum: occurrence, biological activities, and pharmacological functions. Chem Rec 3(3):172–180CrossRefPubMed

31.

Goldstein JL, Brown MS (1990) Regulation of the mevalonate pathway. Nature 343(6257):425CrossRefPubMed

32.

Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME (1999) Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med 221(4):281–293CrossRefPubMed

33.

Chen AW, Miles PG (1996) Biomedical research and the application of mushroom nutriceuticals from Ganoderma lucidum. Mushroom Biology and Mushroom Products Pennsylvania State University, Pennsylvania, 161–175

34.

Liu GT (1999) Recent advances in research of pharmacology and clinical applications of Ganoderma P. Karst. species (Aphyllophoromycetideae) in China. Int J Med Mushrooms 1(1):63–68

35.

Chen R, Yu D (1990) Development of triterpenes from Ganoderma lucidum. Acta Pharm Sin 25:940–953

36.

Gill BS, Sharma P, Kumar R, Kumar S (2016) Misconstrued versatility of Ganoderma lucidum: a key player in multi-targeted cellular signaling. Tumor Biol 37(3):2789–2804CrossRef

37.

Feng L, Yuan L, Du M, Chen Y, Zhang M-H, J-F G, He J-J, Wang Y, Cao W (2013) Anti-lung cancer activity through enhancement of immunomodulation and induction of cell apoptosis of total triterpenes extracted from Ganoderma luncidum (Leyss. ex Fr.) Karst. Molecules 18(8):9966–9981CrossRefPubMed

38.

Chen Y, Lv J, Li K, Xu J, Li M, Zhang W, Pang X (2016) Sporoderm-broken spores of Ganoderma lucidum inhibit the growth of lung cancer: involvement of the Akt/mTOR signaling pathway. Nutr Cancer 68(7):1151–1160CrossRefPubMed

39.

Lin S-B, Li C-H, Lee S-S, Kan L-S (2003) Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci 72(21):2381–2390CrossRefPubMed

40.

Kim TH, Kim JS, Kim ZH, Huang RB, Wang RS (2014) Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis in A549 human lung cancer cells by generating reactive oxygen species and decreasing the mitochondrial membrane potential. Food Sci Biotechnol 23(3):859–864CrossRef

41.

Gill BS, Kumar S (2017) Ganoderic acid modulating TNF and its receptors: in silico and in vitro study. Med Chem Res 26(6):1336–1348CrossRef

42.

Liu R-M, Zhong J-J (2011) Ganoderic acid mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. Phytomedicine 18(5):349–355CrossRefPubMed

43.

Tang W, Liu J-W, Zhao W-M, Wei D-Z, Zhong J-J (2006) Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci 80(3):205–211CrossRefPubMed

44.

Chen N-H, Liu J-W, Zhong J-J (2010) Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression. Pharmacol Rep 62(1):150CrossRefPubMed

45.

J-W X, Zhao W, Zhong J-J (2010) Biotechnological production and application of ganoderic acids. Appl Microbiol Biotechnol 87(2):457–466CrossRef

46.

Zhou L, Shi P, Chen N-H, Zhong J-J (2011) Ganoderic acid Me induces apoptosis through mitochondria dysfunctions in human colon carcinoma cells. Process Biochem 46(1):219–225CrossRef

47.

Chen N-H, Liu J-W, Zhong J-J (2008) Ganoderic acid Me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci 108(2):212–216CrossRefPubMed

48.

Jiang J, Grieb B, Thyagarajan A, Sliva D (2008) Ganoderic acids suppress growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κB signaling. Int J Mol Med 21(5):577–584PubMed

49.

Gill BS, Kumar S (2016) Ganoderic acid targeting multiple receptors in cancer: in silico and in vitro study. Tumor Biol 37(10):14271–14290CrossRef

50.

Gill BS, Kumar S (2015) Differential algorithms-assisted molecular modeling-based identification of mechanistic binding of ganoderic acids. Med Chem Res 24(9):3483–3493CrossRef

51.

Gill BS, Kumar S (2016) Evaluating anti-oxidant potential of ganoderic acid a in STAT 3 pathway in prostate cancer. Mol Biol Rep 43(12):1411–1422CrossRefPubMed

52.

G-S W, J-J L, Guo J-J, Li Y-B, Tan W, Dang Y-Y, Zhong Z-F, Z-T X, Chen X-P, Wang Y-T (2012) Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Fitoterapia 83(2):408–414CrossRef

53.

Chen N-H, Zhong J-J (2009) Ganoderic acid Me induces G 1 arrest in wild-type p53 human tumor cells while G 1/S transition arrest in p53-null cells. Process Biochem 44(8):928–933CrossRef

54.

Li C-H, Chen P-Y, Chang U-M, Kan L-S, Fang W-H, Tsai K-S, Lin S-B (2005) Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells. Life Sci 77(3):252–265CrossRefPubMed

55.

Yue Q-X, Cao Z-W, Guan S-H, Liu X-H, Tao L, W-Y W, Li Y-X, Yang P-Y, Liu X, Guo D-A (2008) Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computer-automated estimation of the possible drug target network. Mol Cell Proteomics 7(5):949–961CrossRefPubMed

56.

Marshall C (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80(2):179–185CrossRefPubMed

57.

Joshi G, Singh PK, Negi A, Rana A, Singh S, Kumar R (2015) Growth factors mediated cell signalling in prostate cancer progression: implications in discovery of anti-prostate cancer agents. Chem Biol Interact 240:120–133CrossRefPubMed

58.

Harhaji Trajković LM, Mijatović SA, Maksimović-Ivanić DD, Stojanović ID, Momčilović MB, Tufegdžić SJ, Maksimović VM, Marjanovi ŽS, Stošić-Grujičić SD (2009) Anticancer properties of Ganoderma lucidum methanol extracts in vitro and in vivo. Nutr Cancer 61(5):696–707CrossRefPubMed

59.

Liu R-M, Li Y-B, Zhong J-J (2012) Cytotoxic and pro-apoptotic effects of novel ganoderic acid derivatives on human cervical cancer cells in vitro. Eur J Pharmacol 681(1):23–33CrossRefPubMed

60.

Gill BS, Kumar S, Navgeet (2017) Ganoderic acid targeting nuclear factor erythroid 2–related factor 2 in lung cancer. Tumor Biol 39 (3):1010428317695530

61.

Zhao H, Zhang Q, Zhao L, Huang X, Wang J, Kang X (2011) Spore powder of Ganoderma lucidum improves cancer-related fatigue in breast cancer patients undergoing endocrine therapy: a pilot clinical trial. Evid Based Complement Alternat Med 2012. https://doi.org/10.1155/2012/809614

62.

Soo TS (1996) Effective dosage of the extract of Ganoderma lucidum in the treatment of various ailments. Mushroom biology and mushroom products. In: Royse DJ (ed). The Pennsylvania State University, University Park pp 177–185

63.

Wanmuang H, Leopairut J, Kositchaiwat C, Wananukul W, Bunyaratvej S (2007) Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder. J Med Assoc Thail 90(1):179

64.

Kawagishi H, Fukuhara F, Sazuka M, Kawashima A, Mitsubori T, Tomita T (1993) 5′-Deoxy-5′-methylsulphinyladenosine, a platelet aggregation inhibitor from Ganoderma lucidum. Phytochemistry 32(2):239–241CrossRef

Titel: Ganoderic acid, lanostanoid triterpene: a key player in apoptosis
verfasst von: Balraj Singh Gill
Navgeet
Richa Mehra
Vicky Kumar
Sanjeev Kumar
Publikationsdatum: 28.10.2017
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 1/2018
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-017-0526-0

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