GB7 acetate, a <i>galbulimima</i> alkaloid from <i>Galbulimima belgraveana</i>, possesses anticancer effects in colorectal cancer cells

Ziyin Li; Lianzhi Mao; Bin Yu; Huahuan Liu; Qiuyu Zhang; Zhongbo Bian; Xudong Zhang; Wenzhen Liao; Suxia Sun

doi:10.1016/j.jpha.2021.06.007

Volume 12 Issue 2

May 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2022 > 12(2): 339-349

Ziyin Li, Lianzhi Mao, Bin Yu, Huahuan Liu, Qiuyu Zhang, Zhongbo Bian, Xudong Zhang, Wenzhen Liao, Suxia Sun. GB7 acetate, a galbulimima alkaloid from Galbulimima belgraveana, possesses anticancer effects in colorectal cancer cells[J]. Journal of Pharmaceutical Analysis, 2022, 12(2): 339-349. doi: 10.1016/j.jpha.2021.06.007

Citation:

Ziyin Li, Lianzhi Mao, Bin Yu, Huahuan Liu, Qiuyu Zhang, Zhongbo Bian, Xudong Zhang, Wenzhen Liao, Suxia Sun. GB7 acetate, a galbulimima alkaloid from Galbulimima belgraveana, possesses anticancer effects in colorectal cancer cells[J]. Journal of Pharmaceutical Analysis, 2022, 12(2): 339-349. doi: 10.1016/j.jpha.2021.06.007

Citation:

PDF( 3692 KB)

GB7 acetate, a galbulimima alkaloid from Galbulimima belgraveana, possesses anticancer effects in colorectal cancer cells

doi: 10.1016/j.jpha.2021.06.007

a. Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China;
b. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450000, China

Funds:

This study was supported by the National Natural Science Foundation of China (Grant No.: 81773429), 2017 High Level University Program Research Foundation for Advanced Talents (Grant No.: C1034220), and Guangdong Natural Science Foundation (Grant No.: 2020A1515010594). We are grateful to Prof. Lewis N. Mander from Australian National University for providing the materials.

Received Date: Jul. 13, 2020
Accepted Date: Jun. 24, 2021
Rev Recd Date: Jun. 23, 2021
Publish Date: Jun. 27, 2021

Abstract

Abstract

GB7 acetate is a galbulimima alkaloid obtained from Galbulimima belgraveana. However, information regarding its structure, biological activities, and related mechanisms is not entirely available. A series of spectroscopic analyses, structural degradation, interconversion, and crystallography were performed to identify the structure of GB7 acetate. The MTT assay was applied to measure cell proliferation on human colorectal cancer HCT 116 cells. The expressions of the related proteins were measured by Western blotting. Transmission electron microscopy (TEM), acridine orange (AO) and monodansylcadaverine (MDC) staining were used to detect the presence of autophagic vesicles and autolysosomes. A transwell assay was performed to demonstrate metastatic capabilities. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) assays were performed to determine the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis activity of HCT 116 cells. The data showed that GB7 acetate suppressed the proliferation and colony-forming ability of HCT 116 cells. Pretreatment with GB7 acetate significantly induced the formation of autophagic vesicles and autolysosomes. GB7 acetate upregulated the expressions of LC3 and Thr172 phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase α (p-AMPKα), which are key elements of autophagy. In addition, GB7 acetate suppressed the metastatic capabilities of HCT 116 cells. Additionally, the production of matrix metallo-proteinase-2 (MMP-2) and MMP-9 was reduced, whereas the expression of E-cadherin (E-cad) was upregulated. Furthermore, GB7 acetate significantly reduced mitochondrial OXPHOS and glycolysis. In conclusion, the structure of the novel Galbulimima alkaloid GB7 acetate was identified. GB7 acetate was shown to have anti-proliferative, pro-autophagic, anti-metastatic, and anti-metabolite capabilities in HCT 116 cells. This study might provide new insights into cancer treatment efficacy and cancer chemoprevention.
- GB7 acetate,
- Galbulimima belgraveana,
- Anti-cancer effects,
- HCT 116 cells

FullText(HTML)

References(44)

References

R. Siegel, C. Desantis, A. Jemal, Colorectal cancer statistics, 2014, CA Cancer J Clin. 64 (2014) 104-117

Cancer Today, International Agency for Research on Cancer. https://gco.iarc.fr/ (Accesseed 15 April 2021).

A.J. Breugom, M. Swets, J.F. Bosset, et al., Adjuvant chemotherapy after preoperative (chemo) radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data, Lancet Oncol. 16 (2015) 200-207

E. Rajesh, L.S. Sankari, L. Malathi, et al., Naturally occurring products in cancer therapy, J Pharm Bioallied Sci. 7 (2015) S181-S183

T.A. Sprague, Plant nomenclature: A reply, J. Bot. 60 (1922) 129-139

P. Lan, A.J. Herlt, A.C. Willis, et al., Structures of New Alkaloids from Rain Forest Trees Galbulimima belgraveana and Galbulimima baccata in Papua New Guinea, Indonesia, and Northern Australia, ACS Omega. 3 (2018) 1912-1921

B. Thomas, Psychoactive properties of Galbulimima bark, J. Psychoactive Drugs. 37 (2005) 109-111

M. Takadoi, K. Yamaguchi, S. Terashima, Synthetic studies on himbacine, a potent antagonist of the muscarinic M2 subtype receptor. Part 2: synthesis and muscarinic M2 subtype antagonistic activity of the novel himbacine congeners modified at the C-3 position of lactone moiety, Bioorg Med Chem. 11 (2003) 1169-1186

M.M. Young, M. Kester, H.G. Wang, Sphingolipids: regulators of crosstalk between apoptosis and autophagy, J. Lipid Res. 54 (2013) 5-19

B.E. Fitzwalter, A. Thorburn, Recent insights into cell death and autophagy, FEBS J. 282 (2015) 4279-4288

S. Deng, M.K. Shanmugam, A.P. Kumar, et al., Targeting autophagy using natural compounds for cancer prevention and therapy, Cancer. 125 (2019) 1228-1246

L. Yuan, S. Wei, J. Wang, et al., Isoorientin induces apoptosis and autophagy simultaneously by reactive oxygen species (ROS)-related p53, PI3K/Akt, JNK, and p38 signaling pathways in HepG2 cancer cells, J. Agric. Food Chem. 62 (2014) 5390-5400

J.J. Bravo-Cordero, L. Hodgson, J. Condeelis, Directed cell invasion and migration during metastasis, Curr. Opin. Cell Biol. 24 (2012) 277-283

C.L. Chaffer, R.A. Weinberg, A perspective on cancer cell metastasis, Science. 331 (2011) 1559-1564

X.D. Xu, S.X. Shao, H.P. Jiang, et al., Warburg effect or reverse Warburg effect? A review of cancer metabolism, Oncol. Res. Treat. 38 (2015) 117-122

O. Warburg, F. Wind, E. Negelein, The metabolism of tumors in the body, J. Gen. Physiol. 8 (1927) 519-530

L. Bai, S. Wang, Targeting apoptosis pathways for new cancer therapeutics, Annu. Rev. Med. 65 (2014) 139-155

C. Bonvin, A. Guillon, M.X. van Bemmelen, et al., Role of the amino-terminal domains of MEKKs in the activation of NF kappa B and MAPK pathways and in the regulation of cell proliferation and apoptosis, Cell Signal. 14 (2002) 123-131

M. Stankiewicz, W. Jonas, E. Hadas, et al., Supravital staining of eosinophils, Int. J. Parasitol. 26 (1996) 445-446

A. Biederbick, H.F. Kern, H.P. Elsasser, Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles, Eur. J. Cell Biol. 66 (1995) 3-14

Y. Kabeya, N. Mizushima, A. Yamamoto, et al., LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation, J. Cell Sci. 117 (2004) 2805-2812

Y. Kabeya, N. Mizushima, T. Ueno, et al., LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing, EMBO J. 19 (2000) 5720-5728

J. Kim, M. Kundu, B. Viollet, et al., AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1, Nat. Cell Biol. 13 (2011) 132-141

P. Vihinen, R. Ala-aho, V.M. Kähäri, Matrix metalloproteinases as therapeutic targets in cancer, Curr. Cancer Drug Targets. 5 (2005) 203-220

C.J. Lee, M.H. Lee, S.M. Yoo, et al., Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway, BMC Cancer. 15 (2015), 576

A. Abe, H. Yamada, S. Moriya, et al., The β-carboline alkaloid harmol induces cell death via autophagy but not apoptosis in human non-small cell lung cancer A549 cells, Biol. Pharm. Bull. 34 (2011) 1264-1272

S. Bialik, S.K. Dasari, A. Kimchi, Autophagy-dependent cell death - where, how and why a cell eats itself to death, J. Cell Sci. 131 (2018), jcs215152

D. Denton, S. Kumar, Autophagy-dependent cell death, Cell Death Differ. 26 (2019) 605-616

M. Zhang, L. Su, Z. Xiao, et al., Methyl jasmonate induces apoptosis and pro-apoptotic autophagy via the ROS pathway in human non-small cell lung cancer, Am. J. Cancer Res. 6 (2016) 187-199

B.Y. Law, S.W. Mok, W.K. Chan, et al., Hernandezine, a novel AMPK activator induces autophagic cell death in drug-resistant cancers, Oncotarget. 7 (2016) 8090-8104

P.J. Roach, AMPK -> ULK1 -> autophagy, Mol. Cell. Biol. 31 (2011) 3082-3084

E.K. Yoon, Y.T. Jeong, X. Li, et al., Glyceollin improves endoplasmic reticulum stress-induced insulin resistance through CaMKK-AMPK pathway in L6 myotubes, J. Nutr. Biochem. 24 (2013) 1053-1061

X. Fan, J. Wang, J. Hou, et al., Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway, J. Transl. Med. 13 (2015), 92

H.P. Kuo, T.C. Chuang, S.C. Tsai, et al., Berberine, an isoquinoline alkaloid, inhibits the metastatic potential of breast cancer cells via Akt pathway modulation, J. Agric. Food Chem. 60 (2012) 9649-9658

M. Paauwe, M. Schoonderwoerd, R. Helderman, et al., Endoglin Expression on Cancer-Associated Fibroblasts Regulates Invasion and Stimulates Colorectal Cancer Metastasis, Clin. Cancer Res. 24 (2018) 6331-6344

M. Stankic, S. Pavlovic, Y. Chin, et al., TGF-β-Id1 signaling opposes Twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition, Cell Rep. 5 (2013) 1228-1242

Y. Yun, R. Gao, H. Yue, et al., Sulfate Aerosols Promote Lung Cancer Metastasis by Epigenetically Regulating the Epithelial-to-Mesenchymal Transition (EMT), Environ. Sci. Technol. 51 (2017) 11401-11411

R.J. Araújo, G.A. Lira, J.A. Vilaça, et al., Prognostic and diagnostic implications of MMP-2, MMP-9, and VEGF-α expressions in colorectal cancer, Pathol. Res. Pract. 211 (2015) 71-77

D.C. Wallace, Mitochondria and cancer, Nat. Rev. Cancer. 12 (2012) 685-698

S.P. Desai, S.N. Bhatia, M. Toner, et al., Mitochondrial localization and the persistent migration of epithelial cancer cells, Biophys. J. 104 (2013), 2077-2088

P.E. Porporato, V.L. Payen, J. Pérez-Escuredo, et al., A mitochondrial switch promotes tumor metastasis, Cell Rep. 8 (2014) 754-766

M. López-Lázaro, Digitoxin as an anticancer agent with selectivity for cancer cells: possible mechanisms involved, Expert Opin. Ther. Targets. 11 (2007) 1043-1053

T.L. Serafim, J.A. Matos, V.A. Sardao, et al., Sanguinarine cytotoxicity on mouse melanoma K1735-M2 cells--nuclear vs. mitochondrial effects, Biochem. Pharmacol. 76 (2008) 1459-1475

V. Estrella, T. Chen, M. Lloyd, et al., Acidity generated by the tumor microenvironment drives local invasion, Cancer Res. 73 (2013) 1524-1535

Relative Articles

Supplements(0)

Cited By

Proportional views