Current Advancements of Plant-Derived Agents for Triple-Negative Breast Cancer Therapy through Deregulating Cancer Cell Functions and Reprogramming Tumor Microenvironment.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Antineoplastic Agents, Phytogenic/*therapeutic use ; Triple Negative Breast Neoplasms/*drug therapy ; Tumor Microenvironment/*drug effects; Animals ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Agents, Phytogenic/pharmacology ; Drug Development ; Female ; Humans ; Triple Negative Breast Neoplasms/immunology ; Triple Negative Breast Neoplasms/pathology ; Tumor Escape/drug effects

Triple-negative breast cancer (TNBC) is defined based on the absence of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. Currently, chemotherapy is the major therapeutic approach for TNBC patients; however, poor prognosis after a standard chemotherapy regimen is still commonplace due to drug resistance. Abnormal tumor metabolism and infiltrated immune or stromal cells in the tumor microenvironment (TME) may orchestrate mammary tumor growth and metastasis or give rise to new subsets of cancer cells resistant to drug treatment. The immunosuppressive mechanisms established in the TME make cancer cell clones invulnerable to immune recognition and killing, and turn immune cells into tumor-supporting cells, hence allowing cancer growth and dissemination. Phytochemicals with the potential to change the tumor metabolism or reprogram the TME may provide opportunities to suppress cancer metastasis and/or overcome chemoresistance. Furthermore, phytochemical intervention that reprograms the TME away from favoring immunoevasion and instead towards immunosurveillance may prevent TNBC metastasis and help improve the efficacy of combination therapies as phyto-adjuvants to combat drug-resistant TNBC. In this review, we summarize current findings on selected bioactive plant-derived natural products in preclinical mouse models and/or clinical trials with focus on their immunomodulatory mechanisms in the TME and their roles in regulating tumor metabolism for TNBC prevention or therapy.

PLoS One. 2014 Feb 03;9(2):e87878. (PMID: 24498388)
Food Funct. 2018 Nov 14;9(11):5682-5696. (PMID: 30310905)
Mini Rev Med Chem. 2021;21(10):1237-1268. (PMID: 33319669)
Nat Rev Drug Discov. 2008 Jun;7(6):489-503. (PMID: 18511927)
Cancer. 1993 Nov 15;72(10):2979-85. (PMID: 8221565)
Oncol Rep. 2020 Feb;43(2):571-580. (PMID: 31894281)
Oncotarget. 2015 Mar 20;6(8):6373-85. (PMID: 25779666)
Molecules. 2021 Apr 12;26(8):. (PMID: 33921192)
J Proteome Res. 2010 Jan;9(1):237-53. (PMID: 19894775)
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):104-114. (PMID: 30663422)
Breast Cancer (Auckl). 2009 Sep 02;3:61-75. (PMID: 19809577)
Clin Cancer Res. 2015 Jun 15;21(12):2722-9. (PMID: 25779953)
N Engl J Med. 2018 Nov 29;379(22):2108-2121. (PMID: 30345906)
Cell Metab. 2016 Jan 12;23(1):27-47. (PMID: 26771115)
Cancer Cell Int. 2021 Sep 6;21(1):468. (PMID: 34488773)
J Biomol Screen. 2011 Dec;16(10):1153-69. (PMID: 22086720)
Cancer Metastasis Rev. 2010 Dec;29(4):723-35. (PMID: 20941528)
Br J Cancer. 2008 Sep 2;99(5):741-9. (PMID: 18728665)
BMC Cancer. 2013 Sep 17;13:421. (PMID: 24044575)
Mol Oncol. 2014 May;8(3):581-95. (PMID: 24484937)
Nature. 2003 Sep 11;425(6954):191-6. (PMID: 12939617)
J Nat Prod. 2020 Mar 27;83(3):770-803. (PMID: 32162523)
Cell Physiol Biochem. 2018;45(2):795-807. (PMID: 29414799)
Ann Oncol. 2021 Sep;32(9):1148-1156. (PMID: 34116144)
Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230)
Stem Cells. 2014 Oct;32(10):2571-82. (PMID: 24891218)
Trends Cancer. 2020 Dec;6(12):989-1001. (PMID: 32718904)
Front Pharmacol. 2017 Jun 29;8:398. (PMID: 28706483)
Front Immunol. 2020 Nov 18;11:584959. (PMID: 33312174)
Breast Cancer Res. 2014 Sep 11;16(5):434. (PMID: 25209360)
Neoplasia. 2005 Apr;7(4):324-30. (PMID: 15967109)
J Nucl Med. 2018 Feb;59(2):183-188. (PMID: 29217734)
Nanomedicine. 2015 Aug;11(6):1399-406. (PMID: 25888278)
Breast Cancer Res Treat. 2019 Apr;174(2):443-452. (PMID: 30604000)
Oncotarget. 2017 May 25;8(34):56942-56958. (PMID: 28915644)
Ann Oncol. 2011 Jan;22(1):98-103. (PMID: 20610479)
Breast Cancer Res Treat. 2011 Nov;130(2):387-98. (PMID: 21188630)
Oncotarget. 2017 Aug 10;8(43):74391-74405. (PMID: 29088795)
J Biosci. 2014 Mar;39(1):139-44. (PMID: 24499798)
J Immunol. 2013 Oct 15;191(8):4141-51. (PMID: 24043896)
J Clin Invest. 2019 Apr 1;129(4):1785-1800. (PMID: 30753167)
Cancer Med. 2013 Aug;2(4):571-82. (PMID: 24156030)
Front Immunol. 2021 May 27;12:656364. (PMID: 34122412)
Oncoimmunology. 2015 May 29;5(1):e1049802. (PMID: 26942057)
Clin Cancer Res. 2017 Jul 1;23(13):3365-3370. (PMID: 28087643)
Aging (Albany NY). 2020 Jan 4;12(1):8-34. (PMID: 31901900)
BMC Cancer. 2010 Dec 03;10:665. (PMID: 21129170)
J Clin Oncol. 2016 Jul 20;34(21):2460-7. (PMID: 27138582)
Adv Drug Deliv Rev. 2013 Mar;65(3):342-7. (PMID: 22776312)
Cancer Metastasis Rev. 2011 Dec;30(3-4):619-40. (PMID: 22037942)
Cancer Chemother Pharmacol. 2016 Feb;77(2):413-27. (PMID: 26793976)
Am J Pathol. 2011 Mar;178(3):997-1008. (PMID: 21356353)
Int J Biol Macromol. 2020 Dec 1;164:3369-3375. (PMID: 32861782)
Genomics. 1995 Jul 1;28(1):74-83. (PMID: 7590750)
Mol Cell. 2002 Oct;10(4):721-33. (PMID: 12419217)
Cell Immunol. 2015 Nov-Dec;298(1-2):88-95. (PMID: 26507910)
Anticancer Res. 1995 Nov-Dec;15(6B):2895-8. (PMID: 8669885)
Breast Cancer Res Treat. 2014 Aug;146(3):557-66. (PMID: 25001612)
Acta Pharmacol Sin. 2016 Aug;37(8):1013-9. (PMID: 27374491)
Eur J Cancer. 2013 Dec;49(18):3900-13. (PMID: 24001613)
Cancer Biol Ther. 2020;21(2):178-188. (PMID: 31663424)
Nat Rev Clin Oncol. 2019 Mar;16(3):151-167. (PMID: 30523282)
PLoS One. 2014 Feb 18;9(2):e88034. (PMID: 24558373)
Trends Immunol. 2003 Jun;24(6):302-6. (PMID: 12810105)
Breast Cancer Res Treat. 2017 Jul;164(2):359-369. (PMID: 28439738)
J Cell Mol Med. 2021 Nov;25(21):10101-10110. (PMID: 34609056)
Mol Pharm. 2021 Jan 4;18(1):74-86. (PMID: 33084332)
Apoptosis. 2017 Oct;22(10):1205-1224. (PMID: 28702823)
J Exp Clin Cancer Res. 2019 May 9;38(1):187. (PMID: 31072371)
Nat Rev Cancer. 2009 Nov;9(11):798-809. (PMID: 19851315)
Sci Rep. 2016 Oct 27;6:36107. (PMID: 27786298)
Science. 2005 Jan 7;307(5706):58-62. (PMID: 15637262)
Free Radic Biol Med. 2012 Apr 15;52(8):1423-36. (PMID: 22342517)
Cancer Cell. 2012 Jan 17;21(1):66-81. (PMID: 22264789)
Nat Rev Mol Cell Biol. 2019 Feb;20(2):69-84. (PMID: 30459476)
Breast Cancer Res Treat. 2018 Oct;171(3):593-605. (PMID: 29971628)
Molecules. 2020 Jul 09;25(14):. (PMID: 32660101)
Int J Mol Sci. 2019 Mar 12;20(5):. (PMID: 30871021)
Breast. 2015 Nov;24 Suppl 2:S36-40. (PMID: 26253813)
Mol Carcinog. 2017 Jan;56(1):208-217. (PMID: 27061264)
Nat Rev Clin Oncol. 2012 Apr 24;9(7):378-90. (PMID: 22525710)
Cancers (Basel). 2020 Jan 13;12(1):. (PMID: 31941087)
Cancer Res. 2017 Aug 1;77(15):3982-3989. (PMID: 28428275)
Nature. 2011 May 19;473(7347):298-307. (PMID: 21593862)
Chin Med J (Engl). 2012 Mar;125(5):775-9. (PMID: 22490573)
Ann Oncol. 2019 Mar 1;30(3):397-404. (PMID: 30475950)
Oncotarget. 2017 Jun 6;8(23):38022-38043. (PMID: 28410237)
Phytomedicine. 2019 Feb 15;54:140-148. (PMID: 30668363)
Int J Mol Sci. 2017 Dec 01;18(12):. (PMID: 29194365)
Mol Cancer Ther. 2013 Feb;12(2):131-40. (PMID: 23270924)
Biomed Pharmacother. 2017 Aug;92:207-214. (PMID: 28544934)
Science. 2009 May 22;324(5930):1029-33. (PMID: 19460998)
Curr Opin Immunol. 2014 Apr;27:16-25. (PMID: 24531241)
Breast Cancer Res Treat. 2015 Nov;154(2):351-7. (PMID: 26536871)
Anticancer Agents Med Chem. 2015;15(10):1285-96. (PMID: 25991545)
Oncogene. 2016 Sep 29;35(39):5155-69. (PMID: 26996666)
Eur J Pharmacol. 2011 Oct 1;668(1-2):99-106. (PMID: 21749863)
Breast Cancer Res Treat. 2018 Feb;167(3):671-686. (PMID: 29063313)
Breast. 2016 Dec;30:39-46. (PMID: 27598996)
Int J Mol Sci. 2020 Jan 08;21(2):. (PMID: 31936346)
EMBO J. 2019 Jul 15;38(14):e100852. (PMID: 31267556)
Int Immunopharmacol. 2019 May;70:110-116. (PMID: 30798159)
Br J Pharmacol. 2010 Feb;159(4):856-71. (PMID: 20105176)
Front Oncol. 2019 Dec 06;9:1370. (PMID: 31921634)
Breast Cancer Res. 2011;13(6):227. (PMID: 22078026)
Histol Histopathol. 2018 Feb;33(2):133-145. (PMID: 28681373)
Transl Oncol. 2011 Dec;4(6):321-7. (PMID: 22190995)
PLoS One. 2013 Jun 17;8(6):e66558. (PMID: 23799116)
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96. (PMID: 24556840)
JAMA Netw Open. 2020 Jan 3;3(1):e1919536. (PMID: 31951276)
Am J Med Sci. 2017 Jul;354(1):54-63. (PMID: 28755734)
Cancer Lett. 2017 May 28;394:52-64. (PMID: 28254410)
PLoS One. 2011;6(5):e20550. (PMID: 21637790)
Br J Cancer. 2013 May 28;108(10):2172-7. (PMID: 23558900)
Ulus Travma Acil Cerrahi Derg. 2011 Jan;17(1):14-8. (PMID: 21341128)
Biol Pharm Bull. 2019 Jun 1;42(6):892-899. (PMID: 30956264)
Molecules. 2020 Dec 17;25(24):. (PMID: 33348838)
Exp Ther Med. 2018 Aug;16(2):830-836. (PMID: 30116337)
J Mammary Gland Biol Neoplasia. 2009 Mar;14(1):67-78. (PMID: 19263197)
In Vivo. 2008 May-Jun;22(3):305-9. (PMID: 18610740)
Cytokine Growth Factor Rev. 2012 Dec;23(6):293-305. (PMID: 22795479)
Anticancer Res. 2017 Nov;37(11):5995-6003. (PMID: 29061778)
Nature. 1992 Mar 26;356(6367):356-8. (PMID: 1549180)
Mol Pharm. 2021 Oct 4;18(10):3862-3870. (PMID: 34470216)
Nutr Res Pract. 2012 Aug;6(4):294-300. (PMID: 22977682)
Biomaterials. 2020 May;240:119791. (PMID: 32109589)
J Clin Invest. 2016 Apr 1;126(4):1208-15. (PMID: 27035812)
Oncogene. 2011 Feb 17;30(7):770-80. (PMID: 20935677)
Mol Pharmacol. 2006 Jan;69(1):195-206. (PMID: 16219905)
Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11091-6. (PMID: 23776241)
Lancet Oncol. 2018 Jan;19(1):40-50. (PMID: 29233559)
Onco Targets Ther. 2015 Feb 26;8:519-28. (PMID: 25750544)
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6948-53. (PMID: 15870198)
BMC Complement Altern Med. 2019 Aug 14;19(1):216. (PMID: 31412862)
Integr Cancer Ther. 2015 Sep;14(5):468-83. (PMID: 26220604)
Oncotarget. 2016 Feb 23;7(8):9322-39. (PMID: 26814431)
Clin Cancer Res. 2019 Mar 15;25(6):1970-1979. (PMID: 30559169)
Sci Rep. 2020 Nov 12;10(1):19639. (PMID: 33184339)
Biomed Pharmacother. 2017 Apr;88:582-594. (PMID: 28152473)
Nat Rev Clin Oncol. 2018 Aug;15(8):471. (PMID: 29872178)
J Biol Chem. 2010 Jun 18;285(25):19106-15. (PMID: 20424164)
Nat Rev Cancer. 2007 Oct;7(10):763-77. (PMID: 17882277)
Colloids Surf B Biointerfaces. 2020 Jul;191:111018. (PMID: 32304917)
Cancer Prev Res (Phila). 2019 Mar;12(3):147-158. (PMID: 30679159)
Oncogenesis. 2017 May 22;6(5):e340. (PMID: 28530705)
Clin Cancer Res. 2016 Sep 15;22(18):4687-97. (PMID: 27106068)
Life Sci. 2018 Nov 15;213:149-157. (PMID: 30352240)
PPAR Res. 2020 Aug 13;2020:3608315. (PMID: 32855630)
JAMA Oncol. 2017 Apr 1;3(4):509-515. (PMID: 27893038)
J Immunol. 2012 Nov 15;189(10):5029-36. (PMID: 23034170)
Nat Cell Biol. 2009 Apr;11(4):492-500. (PMID: 19295512)
Cancer Res. 2000 Jul 1;60(13):3477-83. (PMID: 10910059)
N Engl J Med. 2019 Feb 21;380(8):741-751. (PMID: 30786188)
J Pharmacol Sci. 2016 Feb;130(2):85-93. (PMID: 26810571)
Breast Cancer Res Treat. 2016 Jul;158(2):277-86. (PMID: 27377973)
Anticancer Res. 2015 Jan;35(1):39-46. (PMID: 25550533)
Crit Rev Food Sci Nutr. 2019;59(1):89-101. (PMID: 28799796)
Cell Mol Life Sci. 2019 Feb;76(4):681-697. (PMID: 30382284)
Mediators Inflamm. 2017;2017:9029327. (PMID: 29386753)
Mol Oncol. 2016 Jun;10(6):921-37. (PMID: 27055598)
Prostate. 2018 Feb;78(2):86-94. (PMID: 29105798)
J Control Release. 2020 Jun 10;322:357-374. (PMID: 32243981)
Cancer Res. 2002 Sep 1;62(17):4945-54. (PMID: 12208745)
Cell Immunol. 2021 Oct;368:104423. (PMID: 34399171)
Ann Oncol. 2021 Aug;32(8):983-993. (PMID: 34272041)
J Proteomics. 2021 Jul 15;243:104266. (PMID: 34000456)
Ther Adv Med Oncol. 2017 Apr;9(4):235-252. (PMID: 28491145)
Eur J Clin Pharmacol. 2014 Dec;70(12):1453-63. (PMID: 25248945)
Proc Natl Acad Sci U S A. 2012 May 15;109(20):7765-9. (PMID: 22547799)
Oncol Lett. 2013 Sep;6(3):840-844. (PMID: 24137422)
Mol Cancer. 2010 Feb 09;9:33. (PMID: 20144215)
Nature. 2011 Dec 21;480(7378):480-9. (PMID: 22193102)
Nat Rev Immunol. 2018 May;18(5):309-324. (PMID: 29379212)
Bioeng Transl Med. 2019 Jun 13;4(2):e10129. (PMID: 31249879)
Biology (Basel). 2020 Dec 16;9(12):. (PMID: 33339398)
Asian J Pharm Sci. 2020 May;15(3):385-396. (PMID: 32636956)
J Clin Invest. 2016 Apr 1;126(4):1216-23. (PMID: 26927673)
BMC Complement Altern Med. 2013 Apr 03;13:74. (PMID: 23552194)
Curr Med Chem. 2007;14(19):2024-32. (PMID: 17691944)
Curr Med Chem. 2018;25(27):3162-3213. (PMID: 29446727)
Cells. 2019 Aug 08;8(8):. (PMID: 31398937)
Cancers (Basel). 2020 Dec 18;12(12):. (PMID: 33352874)
Molecules. 2019 Mar 21;24(6):. (PMID: 30901941)
Cancer Immunol Res. 2017 Feb;5(2):94-99. (PMID: 28093447)
BMC Cancer. 2014 Sep 27;14:724. (PMID: 25260874)
Cancer Res. 2016 Aug 1;76(15):4493-503. (PMID: 27325647)
Cell Death Dis. 2013 Feb 21;4:e505. (PMID: 23429291)
Am J Transl Res. 2017 Apr 15;9(4):1934-1942. (PMID: 28469798)
Biomedicines. 2018 Feb 11;6(1):. (PMID: 29439457)
Mol Cancer Ther. 2008 Feb;7(2):263-70. (PMID: 18281512)
Cancers (Basel). 2020 Aug 12;12(8):. (PMID: 32806533)
Br J Pharmacol. 2009 Apr;156(7):1054-66. (PMID: 19298255)
Breast. 2017 Aug;34 Suppl 1:S27-S30. (PMID: 28668293)
PLoS One. 2013 Sep 11;8(9):e73464. (PMID: 24039951)
Biochem Pharmacol. 2005 Oct 15;70(8):1262-6. (PMID: 16139251)
Cell. 2012 Mar 2;148(5):1015-28. (PMID: 22385965)
Medicine (Baltimore). 2015 May;94(17):e774. (PMID: 25929919)
Cancers (Basel). 2014 Sep 05;6(3):1769-92. (PMID: 25198391)
Oncology (Williston Park). 2008 Oct;22(11):1233-9; discussion 1239-40, 1243. (PMID: 18980022)
Int J Mol Med. 2009 Apr;23(4):469-75. (PMID: 19288022)
BBA Clin. 2015 Mar 12;3:257-75. (PMID: 26676166)
Cancer Immunol Immunother. 2021 Dec;70(12):3435-3449. (PMID: 33877384)
Cancer Biol Ther. 2010 Jan;9(1):8-14. (PMID: 19901561)
Carbohydr Polym. 2014 Jan 30;101:871-7. (PMID: 24299850)
PLoS One. 2015 Mar 09;10(3):e0119473. (PMID: 25751270)
Cancer Lett. 2017 Aug 1;400:79-88. (PMID: 28450160)
Front Oncol. 2018 Aug 30;8:356. (PMID: 30234017)
Int J Mol Sci. 2018 Jun 09;19(6):. (PMID: 29890744)
N Engl J Med. 2021 Apr 22;384(16):1529-1541. (PMID: 33882206)
Breast Cancer Res. 2010;12(1):R8. (PMID: 20078855)
Cancer Cell. 2018 Feb 12;33(2):187-201.e10. (PMID: 29438695)
Oncotarget. 2016 Jul 19;7(29):45849-45862. (PMID: 27322681)
Science. 1997 Jan 10;275(5297):218-20. (PMID: 8985016)
Biomed Pharmacother. 2017 Nov;95:18-24. (PMID: 28826092)
Mol Cancer Ther. 2021 Dec;20(12):2553-2567. (PMID: 34583980)
J Cell Sci. 2012 Dec 1;125(Pt 23):5591-6. (PMID: 23420197)
Drugs. 2019 Jul;79(11):1217-1230. (PMID: 31254268)
Sci Rep. 2019 Dec 13;9(1):19107. (PMID: 31836816)
Oncol Res Treat. 2014;37(10):584-9. (PMID: 25342509)
Breast J. 2015 May-Jun;21(3):241-5. (PMID: 25772707)
Pharmacol Res Perspect. 2021 Apr;9(2):e00753. (PMID: 33745223)
Cancers (Basel). 2019 Nov 06;11(11):. (PMID: 31698751)
Am J Chin Med. 2016;44(8):1693-1717. (PMID: 27852125)
Int J Biol Macromol. 2017 Nov;104(Pt B):1853-1859. (PMID: 28359890)
Clin Cancer Res. 2017 Jul 1;23(13):3405-3415. (PMID: 28069724)
PLoS One. 2014 Jul 28;9(7):e102535. (PMID: 25068516)
J Clin Invest. 2011 Jul;121(7):2750-67. (PMID: 21633166)
Curr Opin Immunol. 2012 Apr;24(2):207-12. (PMID: 22236695)
PLoS One. 2013 Oct 02;8(10):e75356. (PMID: 24098377)
Biomolecules. 2019 Nov 27;9(12):. (PMID: 31783552)
Trends Immunol. 2011 Jan;32(1):19-25. (PMID: 21067974)
Adv Biol Regul. 2014 Jan;54:214-21. (PMID: 24080588)

Keywords: drug resistance; metabolism; metastasis; phyto-adjuvants; triple-negative breast cancer; tumor microenvironment

0 (Antineoplastic Agents, Immunological)
0 (Antineoplastic Agents, Phytogenic)

Date Created: 20211224 Date Completed: 20220117 Latest Revision: 20220117

20240104

PMC8703661

10.3390/ijms222413571

34948368