References
Alfarouk, K. O., Verduzco, D., Rauch, C., Muddathir, A. K., Bashir, A.
H. H., Elhassan, G. O. et al . (2014). Glycolysis, tumor
metabolism, cancer growth and dissemination. A new pH-based
etiopathogenic perspective and therapeutic approach to an old cancer
question. Oncoscience, 1(22), 777-802.
Armitage, E. G., & Southam, A. D. (2016). Monitoring cancer prognosis,
diagnosis and treatment efficacy using metabolomics and lipidomics.
Metabolomics, 12 , 146. doi:10.1007/s11306-016-1093-7.
Baba, Y., Tsukuda, M., Mochimatsu, I., Furukawa, S., Kagata, H.,
Nagashima, Y. et al . (2001). Cytostatic effect of inostamycin, an
inhibitor of cytidine 5’-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG):
inositol transferase, on oral squamous cell carcinoma cell lines. Cell
Biol Int, 25 (7), 613-620. doi:10.1006/cbir.2000.0706.
Baci, D., Bruno, A., Bassani, B., Tramacere, M., Mortara, L., Albini,
A., & Noonan, D. M. (2018). Acetyl-l-carnitine is an anti-angiogenic
agent targeting the VEGFR2 and CXCR4 pathways. Cancer Lett, 429 ,
100-116. doi:10.1016/j.canlet.2018.04.018.
Blaser, B., Waselle, L., Dormond-Meuwly, A., Dufour, M., Roulin, D.,
Demartines, N., & Dormond, O. (2012). Antitumor activities of
ATP-competitive inhibitors of mTOR in colon cancer cells. BMC
Cancer, 12 , 86. doi:10.1186/1471-2407-12-86.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., &
Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185 countries. CA
Cancer J Clin, 68 (6), 394-424. doi:10.3322/caac.21492.
Cala, M. P., Aldana, J., Medina, J., Sanchez, J., Guio, J., Wist, J., &
Meesters, R. J. W. (2018). Multiplatform plasma metabolic and lipid
fingerprinting of breast cancer: A pilot control-case study in Colombian
Hispanic women. PLoS One, 13 (2), e0190958.
doi:10.1371/journal.pone.0190958.
Cheng, L., Xia, Z., Bian, X., Li, G., Hu, J., Cao, Y. et al .
(2015). Combination of cetuximab and PP242 synergistically suppress the
progression of wild-type KRAS colorectal carcinoma. Onco Targets
Ther, 8 , 3185-3192. doi:10.2147/OTT.S82453.
Cheng, M., Bhujwalla, Z. M., & Glunde, K. (2016). Targeting
Phospholipid Metabolism in Cancer. Front Oncol, 6 , 266.
doi:10.3389/fonc.2016.00266.
Davis, H. W., Vallabhapurapu, S. D., Chu, Z., Vallabhapurapu, S. L.,
Franco, R. S., Mierzwa, M. et al . (2019). Enhanced
phosphatidylserine-selective cancer therapy with irradiation and
SapC-DOPS nanovesicles. Oncotarget, 10(8), 856-868.
de la Cruz-Lopez, K. G., Castro-Munoz, L. J., Reyes-Hernandez, D. O.,
Garcia-Carranca, A., & Manzo-Merino, J. (2019). Lactate in the
Regulation of Tumor Microenvironment and Therapeutic Approaches. Front
Oncol, 9 , 1143. doi:10.3389/fonc.2019.01143.
Duan, R.-D. (2016). Phospholipid signals and intestinal carcinogenesis.
Scandinavian Journal of Food and Nutrition, 50 (sup2), 45-53.
doi:10.1080/17482970601075703.
Falkenburger, B. H., Jensen, J. B., Dickson, E. J., Suh, B. C., &
Hille, B. (2010). Phosphoinositides: lipid regulators of membrane
proteins. J Physiol, 588 (Pt 17), 3179-3185.
doi:10.1113/jphysiol.2010.192153.
Francipane, M. G., & Lagasse, E. (2013). mTOR pathway in colorectal
cancer: an update. Oncotarget, 5(1), 49-66.
Furse, S., & de Kroon, A. I. (2015). Phosphatidylcholine’s functions
beyond that of a membrane brick. Mol Membr Biol, 32 (4), 117-119.
doi:10.3109/09687688.2015.1066894.
Gao, D., Wang, Y., Xie, W., Yang, T., Jiang, Y., Guo, Y. et al .
(2016). Metabolomics study on the antitumor effect of marine natural
compound flexibilide in HCT-116 colon cancer cell line. J Chromatogr
B, 1014 , 17-23. doi:10.1016/j.jchromb.2016.01.003.
Gibellini, F., & Smith, T. K. (2010). The Kennedy pathway–De novo
synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB
Life, 62 (6), 414-428. doi:10.1002/iub.337.
Goetze, K., Walenta, S., Ksiazkiewicz, M., Kunz-Schughart, L. A., &
Mueller-Klieser, W. (2011). Lactate enhances motility of tumor cells and
inhibits monocyte migration and cytokine release. Int J Oncol,
39 (2), 453-463. doi:10.3892/ijo.2011.1055.
Gulhati, P., Cai, Q., Li, J., Liu, J., Rychahou, P. G., Qiu, S. et
al . (2009). Targeted inhibition of mammalian target of rapamycin
signaling inhibits tumorigenesis of colorectal cancer. Clin Cancer
Res, 15 (23), 7207-7216. doi:10.1158/1078-0432.CCR-09-1249.
Hannun, Y. A., & Obeid, L. M. (2008). Principles of bioactive lipid
signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol,
9 (2), 139-150. doi:10.1038/nrm2329.
Hay, N. (2016). Reprogramming glucose metabolism in cancer: can it be
exploited for cancer therapy? Nat Rev Cancer, 16 (10), 635-649.
doi:10.1038/nrc.2016.77.
Imoto, M., Tanabe, K., Simizu, S., Tashiro, E., Takada, M., & Umezawa,
K. (1998). Inhibition of Cyclin D1 Expression and Induction of Apoptosis
by Inostamycin in Small Cell Lung Carcinoma Cells. Jpn J Cancer Res, 89,
315-322.
Janes, M. R., Limon, J. J., So, L., Chen, J., Lim, R. J., Chavez, M. A.et al . (2010). Effective and selective targeting of leukemia
cells using a TORC1/2 kinase inhibitor. Nat Med, 16 (2), 205-213.
doi:10.1038/nm.2091.
Jin, L., Alesi, G. N., & Kang, S. (2016). Glutaminolysis as a target
for cancer therapy. Oncogene, 35 (28), 3619-3625.
doi:10.1038/onc.2015.447.
Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013). mTOR is a
key modulator of ageing and age-related disease. Nature,
493 (7432), 338-345. doi:10.1038/nature11861.
Jones, D. T., Valli, A., Haider, S., Zhang, Q., Smethurst, E. A., Schug,
Z. T. et al . (2019). 3D Growth of Cancer Cells Elicits
Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers. Mol
Cancer Ther, 18 (2), 376-388. doi:10.1158/1535-7163.MCT-17-0857.
Kim, H. Y., Jin, H., Bae, J., & Choi, H. K. (2019). Metabolic and
lipidomic investigation of the antiproliferative effects of coronatine
against human melanoma cells. Sci Rep, 9 (1), 3140.
doi:10.1038/s41598-019-39990-w.
Knapp, P., Chomicz, K., Swiderska, M., Chabowski, A., & Jach, R.
(2019). Unique Roles of Sphingolipids in Selected Malignant and
Nonmalignant Lesions of Female Reproductive System. Biomed Res
Int, 2019 , 4376583. doi:10.1155/2019/4376583.
Kurabe, N., Hayasaka, T., Ogawa, M., Masaki, N., Ide, Y., Waki, M.et al . (2013). Accumulated phosphatidylcholine (16:0/16:1) in
human colorectal cancer; possible involvement of LPCAT4. Cancer
Sci, 104 (10), 1295-1302. doi:10.1111/cas.12221.
Laplante, M., & Sabatini, D. M. (2012). mTOR signaling in growth
control and disease. Cell, 149 (2), 274-293.
doi:10.1016/j.cell.2012.03.017.
Law, S. H., Chan, M. L., Marathe, G. K., Parveen, F., Chen, C. H., &
Ke, L. Y. (2019). An Updated Review of Lysophosphatidylcholine
Metabolism in Human Diseases. Int J Mol Sci, 20 (5).
doi:10.3390/ijms20051149.
Lu, S., Lu, R., Song, H., Wu, J., Liu, X., Zhou, X. et al .
(2019). Metabolomic study of natrin-induced apoptosis in SMMC-7721
hepatocellular carcinoma cells by ultra-performance liquid
chromatography-quadrupole/time-of-flight mass spectrometry. Int J Biol
Macromol, 124 , 1264-1273. doi:10.1016/j.ijbiomac.2018.11.060.
Mason, E. F., & Rathmell, J. C. (2011). Cell metabolism: an essential
link between cell growth and apoptosis. Biochim Biophys Acta,
1813 (4), 645-654. doi:10.1016/j.bbamcr.2010.08.011.
Mecca, C., Giambanco, I., Bruscoli, S., Bereshchenko, O., Fioretti, B.,
Riccardi, C. et al . (2018). PP242 Counteracts Glioblastoma Cell
Proliferation, Migration, Invasiveness and Stemness Properties by
Inhibiting mTORC2/AKT. Front Cell Neurosci, 12 , 99.
doi:10.3389/fncel.2018.00099.
Melone, M. A. B., Valentino, A., Margarucci, S., Galderisi, U.,
Giordano, A., & Peluso, G. (2018). The carnitine system and cancer
metabolic plasticity. Cell Death Dis, 9 (2), 228.
doi:10.1038/s41419-018-0313-7.
Murfitt, S. A., Zaccone, P., Wang, X., Acharjee, A., Sawyer, Y.,
Koulman, A. et al . (2018). Metabolomics and Lipidomics Study of
Mouse Models of Type 1 Diabetes Highlights Divergent Metabolism in
Purine and Tryptophan Metabolism Prior to Disease Onset. J Proteome
Res, 17 (3), 946-960. doi:10.1021/acs.jproteome.7b00489.
Ogretmen, B. (2018). Sphingolipid metabolism in cancer signalling and
therapy. Nat Rev Cancer, 18 (1), 33-50. doi:10.1038/nrc.2017.96.
Patel, D., & Witt, S. N. (2017). Ethanolamine and
Phosphatidylethanolamine: Partners in Health and Disease. Oxid Med Cell
Longev, 2017 , 4829180. doi:10.1155/2017/4829180.
Qiu, Y., Cai, G., Su, M., Chen, T., Zheng, X., Xu, Y. et al .
(2009). Serum Metabolite Profiling of Human Colorectal Cancer Using
GC-TOFMS and UPLC-QTOFMS. J Proteome Res, 8, 4844-4850.
Qu, Q., Zeng, F., Liu, X., Wang, Q. J., & Deng, F. (2016). Fatty acid
oxidation and carnitine palmitoyltransferase I: emerging therapeutic
targets in cancer. Cell Death Dis, 7 , e2226.
doi:10.1038/cddis.2016.132.
Rivera-Velez, S. M., Broughton-Neiswanger, L. E., Suarez, M. A., Slovak,
J. E., Hwang, J. K., Navas, J. et al . (2019). Understanding the
effect of repeated administration of meloxicam on feline renal cortex
and medulla: A lipidomics and metabolomics approach. J Vet Pharmacol
Ther, 42 (4), 476-486. doi:10.1111/jvp.12788.
Roulin, D., Cerantola, Y., Dormond-Meuwly, A., Demartines, N., &
Dormond, O. (2010). Targeting mTORC2 inhibits colon cancer cell
proliferation in vitro and tumor formation in vivo. Mol Cancer,
9 , 57. doi:10.1186/1476-4598-9-57.
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J. H., Hsu, P. P.,
Bagley, A. F. et al . (2006). Prolonged rapamycin treatment
inhibits mTORC2 assembly and Akt/PKB. Mol Cell, 22 (2), 159-168.
doi:10.1016/j.molcel.2006.03.029.
Stafford, J. H., & Thorpe, P. E. (2011). Increased exposure of
phosphatidylethanolamine on the surface of tumor vascular endothelium.
Neoplasia, 13 (4), 299-308. doi:10.1593/neo.101366.
Takahashi, M., Okazaki, H., Ogata, Y., Takeuchi, K., Ikeda, U., Shimada,
K. (2001). Lysophosphatidylcholine induces apoptosis in human
endothelial cells through a p38-mitogen-activated protein
kinase-dependent mechanism. Atherosclerosis, 161(2002), 387-384.
Tan, L. T., Chan, K. G., Pusparajah, P., Lee, W. L., Chuah, L. H., Khan,
T. M. et al . (2017). Targeting Membrane Lipid a Potential Cancer
Cure? Front Pharmacol, 8 , 12. doi:10.3389/fphar.2017.00012.
Tanaka, K., Sasayama, T., Irino, Y., Takata, K., Nagashima, H., Satoh,
N. et al . (2015). Compensatory glutamine metabolism promotes
glioblastoma resistance to mTOR inhibitor treatment. J Clin
Invest, 125 (4), 1591-1602. doi:10.1172/JCI78239.
Tian, T., Li, X., & Zhang, J. (2019). mTOR Signaling in Cancer and mTOR
Inhibitors in Solid Tumor Targeting Therapy. Int J Mol Sci,
20 (3). doi:10.3390/ijms20030755.
Tsang, C. K., Qi, H., Liu, L. F., & Zheng, X. F. (2007). Targeting
mammalian target of rapamycin (mTOR) for health and diseases. Drug
Discov Today, 12 (3-4), 112-124. doi:10.1016/j.drudis.2006.12.008.
Vallabhapurapu, S.D., Blanco, V. M., Sulaiman, M. K., Vallabhapurapu, S.
L., Chu, Z., Franco RS et al . (2015). Variation in human cancer
cell external phosphatidylserine is regulated by flippase activity and
intracellular calcium. Oncotarget, 6(33), 34375-34388.
Wang, X. W., & Zhang, Y. J. (2014). Targeting mTOR network in
colorectal cancer therapy. World J Gastroenterol, 20 (15),
4178-4188. doi:10.3748/wjg.v20.i15.4178.
Warburg, B. (1956). On the Origin of Cancer Cells. Science, 123(3191),
309-314. DOI: 10.1126/science.123.3191.309.
Xing, X., Zhang, L., Wen, X., Wang, X., Cheng, X., Du, H. et al .
(2014). PP242 suppresses cell proliferation, metastasis, and
angiogenesis of gastric cancer through inhibition of the PI3K/AKT/mTOR
pathway. Anticancer Drugs, 25 (10), 1129-1140.
doi:10.1097/CAD.0000000000000148.
Zeng, Z., Shi, Y. X., Tsao, T., Qiu, Y., Kornblau, S. M., Baggerly, K.
A. et al . (2012). Targeting of mTORC1/2 by the mTOR kinase
inhibitor PP242 induces apoptosis in AML cells under conditions
mimicking the bone marrow microenvironment. Blood, 120 (13),
2679-2689. doi:10.1182/blood-2011-11-393934.
Zhang, Y. J., Dai, Q., Sun, D. F., Xiong, H., Tian, X. Q., Gao, F. H.et al . (2009). mTOR signaling pathway is a target for the
treatment of colorectal cancer. Ann Surg Oncol, 16 (9), 2617-2628.
doi:10.1245/s10434-009-0555-9.
Zhang, Z., Zhang, G., Kong, C., & Gong, D. (2016). PP242 suppresses
bladder cancer cell proliferation and migration through deactivating the
mammalian target of rapamycin complex 2/AKT1 signaling pathway. Mol Med
Rep, 13 (1), 333-338. doi:10.3892/mmr.2015.4528.
Zheng, Z., Xu, L., Zhang, S., Li, W., Tou, F., He, Q. et al .
(2017). Peiminine inhibits colorectal cancer cell proliferation by
inducing apoptosis and autophagy and modulating key metabolic pathways.
Oncotarget, 8 (29), 47619-47631. doi:10.18632/oncotarget.17411.
Table 1. List of altered identified metabolites in plasma due to the
effects of PP242 using metabolomics and lipidomics approaches.