题名

Spatholobus suberectus inhibits lipogenesis and tumorigenesis in triple-negative breast cancer via activation of AMPK-ACC and K-Ras-ERK signaling pathway

DOI

10.1016/j.jtcme.2023.09.002

作者

Xiaohui Zeng;Guowei Gong;Kumar Ganesan;Yi Wen;Qingqing Liu;Juncheng Zhuo;Jianming Wu;Jianping Chen

关键词

Spatholobi suberectus ; Lipogenesis ; TNBC ; Therapy ; Natural product ; Proteomic and metabolomic analysis

期刊名称

Journal of Traditional and Complementary Medicine

卷期/出版年月

13卷6期(2023 / 11 / 01)

页次

623 - 638

内容语文

英文

中文摘要

Background and aim: Triple-negative breast cancer (TNBC) is a highly invasive type of breast cancer with a poor prognosis. Currently, there are no effective management strategies for TNBC. Earlier, our lab reported the percolation of Spatholobus suberectus for the treatment of breast cancer. Lipid metabolic reprogramming is a hallmark of cancer. However, the anti-TNBC efficiency of S. suberectus extract and its causal mechanism for preventing lipogenesis have not been fully recognized. Hence, the present study aimed to investigate the inhibitory role of S. suberectus extract on lipogenesis and tumorigenesis in TNBC in vitro and in vivo by activating AMPK-ACC and K-Ras-ERK signaling pathways using lipidomic and metabolomic techniques. Experimental procedure: Dried stems of S. suberectus extract inhibited lipogenesis and tumorigenesis and promoted fatty acid oxidation as demonstrated by the identification of the metabolites and fatty acid markers using proteomic and metabolomic analysis, qPCR, and Western blot. Results and conclusion: The results indicated that S. suberectus extract promotes fatty acid oxidation and suppresses lipogenic metabolites and biomarkers, thereby preventing tumorigenesis via the AMPK-ACC and K-Ras-ERK signaling pathways. On the basis of this preclinical evidence, we suggest that this study represents a milestone and complements Chinese medicine. Further studies remain underway in our laboratory to elucidate the active principles of S. suberectus extract. This study suggests that S. suberectus extract could be a promising therapy for TNBC.

主题分类 醫藥衛生 > 中醫藥學
参考文献
  1. Estimated Number of New Cases in 2020, Worldwide, Both Sexes, All Age; 2021. https://gco.iarc.fr.
  2. Adeyinka, A,Nui, Y,Cherlet, T,Snell, L,Watson, PH,Murphy, LC(2002).Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression.Clin Cancer Res,8(6),1747-1753.
  3. Amendola, CR,Mahaffey, JP,Parker, SJ(2019).KRAS4A directly regulates hexokinase 1.Nature,576(7787),482-486.
  4. Anderson, JD,Johansson, HJ,Graham, CS(2016).Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-KappaB signaling.Stem Cell,34(3),601-613.
  5. Bartolacci, C,Andreani, C,Vale, G(2022).Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer.Nat Commun,13(1),4327.
  6. Beloribi-Djefaflia, S,Vasseur, S,Guillaumond, F(2016).Lipid metabolic reprogramming in cancer cells.Oncogenesis,5(1),e189-e189.
  7. Blücher, C,Stadler, SC(2017).Obesity and breast cancer: current insights on the role of fatty acids and lipid metabolism in promoting breast cancer growth and progression.Front Endocrinol,8,293.
  8. Chen, HL,Yang, J,Fu, YF,Meng, XN,Zhao, WD,Hu, TJ(2017).Effect of total flavonoids of Spatholobus suberectus Dunn on PCV2 induced oxidative stress in RAW264.7 cells.BMC Compl Alternative Med,17(1),244.
  9. Chen, M,Huang, J(2019).The expanded role of fatty acid metabolism in cancer: new aspects and targets.Precis Clin Med,2(3),183-191.
  10. Chen, SR,Wang, AQ,Lin, LG,Qiu, HC,Wang, YT,Wang, Y(2016).In vitro study on anti-hepatitis C virus activity of Spatholobus suberectus Dunn.Molecules,21(10)
  11. Cho, H,Chung, B,Kim, CK,Oh, DC,Oh, KB,Shin, J(2017).Spatholobus suberectus Dunn. constituents inhibit sortase A and Staphylococcus aureus cell clumping to fibrinogen.Arch Pharm Res,40(4),518-523.
  12. Fang, K,Wu, F,Chen, G(2019).Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells.BMC Compl Alternative Med,19(1),255.
  13. Feng, RM,Zong, YN,Cao, SM,Xu, RH(2019).Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?.Cancer Commun,39(1),22.
  14. Feng, WW,Kurokawa, M(2020).Lipid metabolic reprogramming as an emerging mechanism of resistance to kinase inhibitors in breast cancer.Cancer Drug Resist,3(1),1-17.
  15. Fu, YF,Jiang, LH,Zhao, WD(2017).Immunomodulatory and antioxidant effects of total flavonoids of Spatholobus suberectus Dunn on PCV2 infected mice.Sci Rep,7(1),8676.
  16. Gao, L,Xu, Z,Huang, Z(2020).CPI-613 rewires lipid metabolism to enhance pancreatic cancer apoptosis via the AMPK-ACC signaling.J Exp Clin Cancer Res,39(1),73.
  17. Giudetti, AM,De Domenico, S,Ragusa, A(2019).A specific lipid metabolic profile is associated with the epithelial mesenchymal transition program.Biochim Biophys Acta Mol Cell Biol Lipids,1864(3),344-357.
  18. Goodwin, CM,Waters, AM,Klomp, JE(2023).Combination therapies with CDK4/6 inhibitors to treat KRAS-mutant pancreatic cancer.Cancer Res,83(1),141-157.
  19. Granchi, C(2018).ATP citrate lyase (ACLY) inhibitors: an anti-cancer strategy at the crossroads of glucose and lipid metabolism.Eur J Med Chem,157,1276-1291.
  20. Guo, D,Bell, EH,Mischel, P,Chakravarti, A(2014).Targeting SREBP-1-driven lipid metabolism to treat cancer.Curr Pharmaceut Des,20(15),2619-2626.
  21. Hadad, SM,Baker, L,Quinlan, PR(2009).Histological evaluation of AMPK signaling in primary breast cancer.BMC Cancer,9,307.
  22. Han, J,Lim, W,You, D(2019).Chemoresistance in the human triple-negative breast cancer cell line MDA-MB-231 induced by doxorubicin gradient is associated with epigenetic alterations in histone deacetylase.JAMA Oncol,2019,1345026.
  23. Hoeflich, KP,O'Brien, C,Boyd, Z(2009).In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models.Clin Cancer Res,15(14),4649-4664.
  24. Hu, H,Cheng, R,Wang, Y(2023).Oncogenic KRAS signaling drives evasion of innate immune surveillance in lung adenocarcinoma by activating CD47.J Clin Invest,133(2)
  25. Hu, X,Zhang, Y,Yu, H(2022).The role of YAP1 in survival prediction, immune modulation, and drug response: a pan-cancer perspective.Front Immunol,13,1012173.
  26. Huang, S,Chong, N,Lewis, NE,Jia, W,Xie, G,Garmire, LX(2016).Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis.Genome Med,8(1),34.
  27. Inami, K,Asada, Y,Harada, T,Okayama, Y,Usui, N,Mochizuki, M(2019).Antimutagenic components in Spatholobus suberectus Dunn against N-methyl-N-nitrosourea.Gene Environ,41,22.
  28. Isakoff, SJ(2010).Triple-negative breast cancer: role of specific chemotherapy agents.Cancer J,16(1),53-61.
  29. Kim, H,Yi, SS,Lee, HK(2018).Antiproliferative effect of vine stem extract from Spatholobus suberectus Dunn on rat C6 glioma cells through regulation of ROS, mitochondrial depolarization, and P21 protein expression.Nutr Cancer,70(4),605-619.
  30. Kim, HJ,Cho, SD,Kim, J(2013).Apoptotic effect of tolfenamic acid on MDA-MB231 breast cancer cells and xenograft tumors.J Clin Biochem Nutr,53(1),21-26.
  31. Krug, K,Jaehnig, EJ,Satpathy, S(2020).Proteogenomic landscape of breast cancer tumorigenesis and targeted therapy.Cell,183(5),1436-1456.e1431.
  32. Lebert, JM,Lester, R,Powell, E,Seal, M,McCarthy, J(2018).Advances in the systemic treatment of triple-negative breast cancer.Curr Oncol,25(Suppl 1),S142-S150.
  33. Li, K,Chen, L,Lin, Z(2020).Role of the AMPK/ACC signaling pathway in TRPP2- mediated head and neck cancer cell proliferation.BioMed Res Int,2020,4375075.
  34. Lim, HJ,Park, MN,Kim, C(2019).MiR-657/ATF2 signaling pathway has a critical role in Spatholobus suberectus Dunn extract-induced apoptosis in U266 and U937 cells.Cancers,11(2)
  35. Liu, P,Wang, Y,Li, X(2019).Targeting the untargetable KRAS in cancer therapy.Acta Pharm Sin B,9(5),871-879.
  36. Liu, Q,Kwan, KY,Cao, T(2022).Broad-spectrum antiviral activity of Spatholobus suberectus Dunn against SARS-CoV-2, SARS-CoV-1, H5N1, and other enveloped viruses.Phytother Res,36(8),3232-3247.
  37. Liu, YQ,Wang, XL,He, DH,Cheng, YX(2021).Protection against chemotherapy- and radiotherapy-induced side effects: a review based on the mechanisms and therapeutic opportunities of phytochemicals.Phytomedicine,80,153402.
  38. Loi, S,Dushyanthen, S,Beavis, PA(2016).RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors.Clin Cancer Res,22(6),1499-1509.
  39. Luo, H,Chen, CY,Li, X(2021).Increased lipogenesis is critical for self-renewal and growth of breast cancer stem cells: impact of omega-3 fatty acids.Stem Cell,39(12),1660-1670.
  40. Mohammad, RM,Muqbil, I,Lowe, L(2015).Broad targeting of resistance to apoptosis in cancer.Semin Cancer Biol,35(Suppl),S78-S103.
  41. Murakami, M(2017).Lipoquality control by phospholipase A(2) enzymes.Proc Jpn Acad Ser B Phys Biol Sci,93(9),677-702.
  42. Muyinda, IJ,Park, JG,Jang, EJ,Yoo, BC(2021).KRAS, A prime mediator in pancreatic lipid synthesis through extra mitochondrial glutamine and citrate metabolism.Int J Mol Sci,22(10)
  43. Nedeljkovic, M,Damjanovic, A(2019).Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge.Cells,8(9)
  44. Nguyen, PL,Taghian, AG,Katz, MS(2008).Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy.J Clin Oncol,26(14),2373-2378.
  45. Nickels, JT, Jr(2018).New links between lipid accumulation and cancer progression.J Biol Chem,293(17),6635-6636.
  46. Pang, Y,Xu, X,Xiang, X(2021).High fat activates O-GlcNAcylation and affects AMPK/ACC pathway to regulate lipid metabolism.Nutrients,13(6)
  47. Park, JK,Coffey, NJ,Limoges, A,Le, A(2018).The heterogeneity of lipid metabolism in cancer.Adv Exp Med Biol,1063,33-55.
  48. Park, W,Ahn, CH,Cho, H,Kim, CK,Shin, J,Oh, KB(2017).Inhibitory effects of flavonoids from Spatholobus suberectus on sortase A and sortase A-mediated aggregation of Streptococcus mutans.J Microbiol Biotechnol,27(8),1457-1460.
  49. Peng, F,Meng, CW,Zhou, QM,Chen, JP,Xiong, L(2016).Cytotoxic evaluation against breast cancer cells of isoliquiritigenin analogues from Spatholobus suberectus and their synthetic derivatives.J Nat Prod,79(1),248-251.
  50. Peng, F,Tang, H,Du, J,Chen, J,Peng, C(2021).Isoliquiritigenin suppresses EMT-induced metastasis in triple-negative breast cancer through miR-200c/C-JUN/[Formula: see text]-catenin.Am J Chin Med,49(2),505-523.
  51. Peng, F,Tang, H,Liu, P(2017).Isoliquiritigenin modulates miR-374a/PTEN/Akt axis to suppress breast cancer tumorigenesis and metastasis.Sci Rep,7(1),9022.
  52. Peng, F,Wang, L,Xiong, L,Tang, H,Du, J,Peng, C(2022).Maackiain modulates miR-374a/gadd45a Axis to inhibit triple-negative breast cancer initiation and progression.Front Pharmacol,13,806869.
  53. Peng, F,Xiong, L,Peng, C(2020).(-)-Sativan inhibits tumor development and regulates miR-200c/PD-L1 in triple negative breast cancer cells.Front Pharmacol,11,251.
  54. Peng, F,Zhu, H,Meng, CW,Ren, YR,Dai, O,Xiong, L(2019).New isoflavanes from Spatholobus suberectus and their cytotoxicity against human breast cancer cell lines.Molecules,24(18)
  55. Prasad, B,Vrana, M,Mehrotra, A,Johnson, K,Bhatt, DK(2017).The promises of quantitative proteomics in precision medicine.J Pharmaceut Sci,106(3),738-744.
  56. Prior, IA,Hood, FE,Hartley, JL(2020).The frequency of ras mutations in cancer.Cancer Res,80(14),2969-2974.
  57. Qu, C,Yuan, ZW,Yu, XT(2017).Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.Pharmacol Res,121,70-82.
  58. Quan, J,Bode, AM,Luo, X(2021).ACSL family: the regulatory mechanisms and thera-peutic implications in cancer.Eur J Pharmacol,909,174397.
  59. Rochlitz, CF,Scott, GK,Dodson, JM(1989).Incidence of activating ras oncogene mutations associated with primary and metastatic human breast cancer.Cancer Res,49(2),357-360.
  60. Rozeveld, CN,Johnson, KM,Zhang, L,Razidlo, GL(2020).KRAS controls pancreatic cancer cell lipid metabolism and invasive potential through the lipase HSL.Cancer Res,80(22),4932-4945.
  61. Simeone, P,Tacconi, S,Longo, S(2021).Expanding roles of de novo lipogenesis in breast cancer.Int J Environ Res Publ Health,18(7),3575.
  62. Song, L,Liu, Z,Hu, HH(2020).Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy.Nat Commun,11(1),5842.
  63. Sui, X,Chen, R,Wang, Z(2013).Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment.Cell Death Dis,4,e838.
  64. Sun, JQ,Zhang, GL,Zhang, Y(2016).Spatholobus suberectus column extract inhibits estrogen receptor positive breast cancer via suppressing ER MAPK PI3K/AKT pathway.Evid Based Complement Alternat Med,2016,2934340.
  65. Tang, RN,Qu, XB,Guan, SH,Xu, PP,Shi, YY,Guo, DA(2012).Chemical constituents of Spatholobus suberectus.Chin J Nat Med,10(1),32-35.
  66. Thiery, JP,Acloque, H,Huang, RY,Nieto, MA(2009).Epithelial-mesenchymal transitions in development and disease.Cell,139(5),871-890.
  67. Wang, J,Wong, YK,Zhang, J(2017).Drug target identification using an iTRAQ-based quantitative chemical proteomics approach-based on a target profiling study of andrographolide.Methods Enzymol,586,291-309.
  68. Wang, N,Wang, Z,Wang, Y(2015).Dietary compound isoliquiritigenin prevents mammary carcinogenesis by inhibiting breast cancer stem cells through WIF1 demethylation.Oncotarget,6(12),9854-9876.
  69. Wang, Y,Yu, R-Y,He, Q-Y(2015).Proteomic analysis of anticancer TCMs targeted at mitochondria.Evid base Compl Alternative Med,2015,539260.
  70. Wang, Z,Wang, D,Han, S(2013).Bioactivity-guided identification and cell signaling technology to delineate the lactate dehydrogenase A inhibition effects of Spatholobus suberectus on breast cancer.PLoS One,8(2),e56631.
  71. Wang, Z,Wang, N,Han, S(2013).Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via VEGF/VEGFR-2 signaling pathway.PLoS One,8(7),e68566.
  72. Wang, ZY,Wang, DM,Loo, TY(2011).Spatholobus suberectus inhibits cancer cell growth by inducing apoptosis and arresting cell cycle at G2/M checkpoint.J Ethnopharmacol,133(2),751-758.
  73. Xiao, Y,Ma, D,Yang, YS(2022).Comprehensive metabolomics expands precision medicine for triple-negative breast cancer.Cell Res,32(5),477-490.
  74. Yan, X,Li, SY,Wang, MH,Xu, RF,Zheng, J,Ren, MZ(2018).Liver and kidney function of E-waste dismantling workers and potential influencing factors.Huanjing Kexue,39(2),953-960.
  75. Yang, J,Mo, J,Dai, J(2021).Cetuximab promotes RSL3-induced ferroptosis by suppressing the Nrf2/HO-1 signalling pathway in KRAS mutant colorectal cancer.Cell Death Dis,12(11),1079.
  76. You, MK,Kim, MS,Jeong, KS,Kim, E,Kim, YJ,Kim, HA(2016).Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells.Nutr Res Prac,10(2),139-147.
  77. Zhang, F,Ganesan, K,Liu, Q,Chen, J(2022).A review of the pharmacological potential of Spatholobus suberectus Dunn on cancer.Cells,11(18)
  78. Zhang, F,Liu, Q,Ganesan, K(2021).The antitriple negative breast cancer efficacy of Spatholobus suberectus Dunn on ROS-induced noncanonical inflammasome pyroptotic pathway.Oxid Med Cell Longev,2021,5187569.
  79. Zhang, Y,Li, F,Patterson, AD(2012).Abcb11 deficiency induces cholestasis coupled to impaired b-fatty acid oxidation in mice.J Biol Chem,287(29),24784-24794.