Login Register Cart 0
Generic placeholder image

Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Narrative Testimony and Characteristics of Rottlerin for the Treatment of Various Kinds of Cancer

Author(s): Lopamudra Mishra, Lakshmi Kumari, Preeti Patel, Amrita Singh and Balak Das Kurmi*

Volume 20, Issue 3, 2024

Published on: 08 October, 2023

Page: [233 - 242] Pages: 10

DOI: 10.2174/0115733947244863230928095352

Price: $65

Abstract

From ancient times until now, scientists have focused on herbal medicaments for treating various diseases. Rottlerin, a potent PKCδ inhibitor, is one of the greatest herbal medications. Over the years, it was identified that rottlerin has several cellular and molecular targets that could be involved in the fight against cancer. The past and present research has clearly shown that rottlerin inhibits the transcription factors, enzymes, and signaling molecules that regulate the death and life of cancer cells. Although the anticancer property of rottlerin has primarily been attributed to the induction of autophagy and apoptosis, current research has revealed the existence of different damage pathways. The major part described in this mini-review is the antitumor/anticancer effects of rottlerin in various organs of the human body affected by breast cancer, pancreatic cell cancer, bladder cancer, NSCLC, prostate cancer, ovarian cancer, nasopharyngeal cancer, etc.

Keywords: Rottlerin, anti-cancer, mTOR signaling, PKCδ inhibitor, anti-viral, antiangiogenic.

Next »
Graphical Abstract

[1]
Hong KKC, Ho KKK, Bhadbhade M, Ball GE, Black DS, Kumar N. The mosaic of rottlerin: The sequel. J Nat Prod 2019; 82(5): 1190-9.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00917] [PMID: 31017784]
[2]
Ringshausen I, Weick K, Oelsner M, Peschel C, Decker TJB. Inhibition of protein kinase C (PKC) delta with rottlerin induces apoptosis in B-CLL cells. Aug Chemotherap CytotInhi AntiapSurvSig 2004; 104(11): 2800.
[3]
Pandey S, Chatterjee A, Jaiswal S, Kumar S, Ramachandran R, Srivastava KK. Protein kinase C-δ inhibitor, rottlerin inhibits growth and survival of mycobacteria exclusively through Shikimate kinase. Biochem Biophys Res Commun 2016; 478(2): 721-6.
[http://dx.doi.org/10.1016/j.bbrc.2016.08.014] [PMID: 27498028]
[4]
Huang WL, Hsiung MH, Dai W, Hu SSJ. Rottlerin, BDNF, and the impairment of inhibitory avoidance memory. Psychopharmacology 2021; 238(2): 421-39.
[http://dx.doi.org/10.1007/s00213-020-05690-x] [PMID: 33146738]
[5]
Maioli E, Daveri E, Maellaro E, Ietta F, Cresti L, Valacchi G. Non-conventional rottlerin anticancer properties. Arch Biochem Biophys 2018; 645: 50-3.
[http://dx.doi.org/10.1016/j.abb.2018.03.009] [PMID: 29545132]
[6]
Siposova K, Kozar T, Huntosova V, Tomkova S, Musatov A. Inhibition of amyloid fibril formation and disassembly of pre-formed fibrils by natural polyphenol rottlerin. Biochim Biophys Acta Proteins Proteomics 2019; 1867(3): 259-74.
[http://dx.doi.org/10.1016/j.bbapap.2018.10.002] [PMID: 30316862]
[7]
Maioli E, Greci L, Soucek K, et al. Rottlerin Inhibits ROS formation and prevents NF B activation in MCF-7 and HT-29 Cells. J Biomed Biotechnol 2009; 2009: 742936.
[8]
Torricelli C, Fortino V, Capurro E, et al. Rottlerin inhibits the nuclear factor κB/Cyclin-D1 cascade in MCF-7 breast cancer cells. Life Sci 2008; 82(11-12): 638-43.
[http://dx.doi.org/10.1016/j.lfs.2007.12.020] [PMID: 18261747]
[9]
Valacchi G, Pecorelli A, Sticozzi C, et al. Rottlerin exhibits antiangiogenic effects in vitro. Chem Biol Drug Des 2011; 77(6): 460-70.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01121.x] [PMID: 21435184]
[10]
Ishii R, Horie M, Saito K, Arisawa M, Kitanaka S. Prostaglandin E2 production and induction of prostaglandin endoperoxide synthase-2 is inhibited in a murine macrophage-like cell line, RAW 264.7, by Mallotus japonicus phloroglucinol derivatives. Biochim Biophys Acta, Gen Subj 2002; 1571(2): 115-23.
[http://dx.doi.org/10.1016/S0304-4165(02)00200-3] [PMID: 12049791]
[11]
Ma J, Hou Y, Xia J, Zhu X, Wang ZP. Tumor suppressive role of rottlerin in cancer therapy. Am J Transl Res 2018; 10(11): 3345-56.
[PMID: 30662591]
[12]
Lee TH, Chen JL, Liu PS, Tsai MM, Wang SJ, Hsieh HL. Rottlerin, a natural polyphenol compound, inhibits upregulation of matrix metalloproteinase-9 and brain astrocytic migration by reducing PKC-δ-dependent ROS signal. J Neuroinflammation 2020; 17(1): 177.
[http://dx.doi.org/10.1186/s12974-020-01859-5] [PMID: 32505192]
[13]
Qi P, He Z, Zhang L, Fan Y, Wang Z. Rottlerin-induced autophagy leads to apoptosis in bladder cancer cells. Oncol Lett 2016; 12(6): 4577-83.
[http://dx.doi.org/10.3892/ol.2016.5255] [PMID: 28101215]
[14]
Ringshausen I, Oelsner M, Weick K, Bogner C, Peschel C, Decker T. Mechanisms of apoptosis-induction by rottlerin: therapeutic implications for B-CLL. Leukemia 2006; 20(3): 514-20.
[http://dx.doi.org/10.1038/sj.leu.2404113] [PMID: 16437144]
[15]
Alipour M. Molecular mechanism of helicobacter pylori-induced gastric cancer. J Gastrointest Cancer 2021; 52(1): 23-30.
[http://dx.doi.org/10.1007/s12029-020-00518-5] [PMID: 32926335]
[16]
Nasr R, Shamseddine A, Mukherji D, Nassar F, Temraz S. The crosstalk between microbiome and immune response in gastric cancer. Int J Mol Sci 2020; 21(18): 6586.
[http://dx.doi.org/10.3390/ijms21186586] [PMID: 32916853]
[17]
Engstrand L, Graham DY. Microbiome and gastric cancer. Dig Dis Sci 2020; 65(3): 865-73.
[http://dx.doi.org/10.1007/s10620-020-06101-z] [PMID: 32040665]
[18]
Song J, Zhou Y, Gong Y, Liu H, Tang L. Rottlerin promotes autophagy and apoptosis in gastric cancer cell lines. Mol Med Rep 2018; 18(3): 2905-13.
[http://dx.doi.org/10.3892/mmr.2018.9293] [PMID: 30015872]
[19]
Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol 2022; 77(6): 1598-606.
[http://dx.doi.org/10.1016/j.jhep.2022.08.021] [PMID: 36208844]
[20]
Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: Trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019; 16(10): 589-604.
[http://dx.doi.org/10.1038/s41575-019-0186-y] [PMID: 31439937]
[21]
Shi J, Ning H, He G, et al. Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma. Mol Med Rep 2018; 17(1): 459-64.
[PMID: 29115596]
[22]
Wang Z, Shen G, Xie J, Li B, Gao Q. Rottlerin upregulates DDX3 expression in hepatocellular carcinoma. Biochem Biophys Res Commun 2018; 495(1): 1503-9.
[http://dx.doi.org/10.1016/j.bbrc.2017.11.198] [PMID: 29203243]
[23]
Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol 2022; 95(1130): 20211033.
[http://dx.doi.org/10.1259/bjr.20211033] [PMID: 34905391]
[24]
Liang Y, Zhang H, Song X, Yang Q. Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets. Semin Cancer Biol 2020; 60: 14-27.
[http://dx.doi.org/10.1016/j.semcancer.2019.08.012] [PMID: 31421262]
[25]
Kumar D, Shankar S, Srivastava RK. Rottlerin-induced autophagy leads to the apoptosis in breast cancer stem cells: Molecular mechanisms. Mol Cancer 2013; 12(1): 171.
[http://dx.doi.org/10.1186/1476-4598-12-171] [PMID: 24359639]
[26]
Manhas D, Mir KB, Tripathi N, et al. Rottlerin promotes anti-metastatic events by ameliorating pharmacological parameters of paclitaxel: An in-vivo investigation in the orthotopic mouse model of breast cancer. Chem Biol Interact 2022; 366: 110109.
[http://dx.doi.org/10.1016/j.cbi.2022.110109] [PMID: 35995259]
[27]
Yin X, Zhang Y, Su J, et al. Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells. Oncotarget 2016; 7(41): 66512-24.
[http://dx.doi.org/10.18632/oncotarget.11614] [PMID: 27582552]
[28]
Stoffel EM, Murphy CC. Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults. Gastroenterology 2020; 158(2): 341-53.
[http://dx.doi.org/10.1053/j.gastro.2019.07.055] [PMID: 31394082]
[29]
Lannagan TRM, Jackstadt R, Leedham SJ, Sansom OJ. Advances in colon cancer research: In vitro and animal models. Curr Opin Genet Dev 2021; 66: 50-6.
[http://dx.doi.org/10.1016/j.gde.2020.12.003] [PMID: 33422950]
[30]
Jahanafrooz Z, Mosafer J, Akbari M, Hashemzaei M, Mokhtarzadeh A, Baradaran B. Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment. J Cell Physiol 2020; 235(5): 4153-66.
[http://dx.doi.org/10.1002/jcp.29337] [PMID: 31647128]
[31]
Park EJ, Lim JH, Nam SI, Park JW, Kwon TK. Rottlerin induces heme oxygenase-1 (HO-1) up-regulation through reactive oxygen species (ROS) dependent and PKC δ-independent pathway in human colon cancer HT29 cells. Biochimie 2010; 92(1): 110-5.
[http://dx.doi.org/10.1016/j.biochi.2009.10.001] [PMID: 19833168]
[32]
Juneja M, Kobelt D, Walther W, et al. Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1. PLoS Biol 2017; 15(6): e2000784.
[http://dx.doi.org/10.1371/journal.pbio.2000784] [PMID: 28570591]
[33]
Lim JH, Park JW, Kim SH, Choi YH, Choi KS, Kwon TK. Rottlerin induces pro-apoptotic endoplasmic reticulum stress through the protein kinase C-delta-independent pathway in human colon cancer cells. Apoptosis Int J prog cell death 2008; 13(11): 1378-85.
[34]
Anaba EL. Comparative study of cutaneous melanoma and its associated issues between people of African decent and Caucasians. Dermatol Ther 2021; 34(2): e14790.
[http://dx.doi.org/10.1111/dth.14790] [PMID: 33480165]
[35]
Dzwierzynski WW. Melanoma risk factors and prevention. Clin Plast Surg 2021; 48(4): 543-50.
[http://dx.doi.org/10.1016/j.cps.2021.05.001] [PMID: 34503715]
[36]
Rastrelli M, Tropea S, Rossi CR, Alaibac M. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo 2014; 28(6): 1005-11.
[PMID: 25398793]
[37]
Ietta F, Valacchi G, Benincasa L, Pecorelli A, Cresti L, Maioli E. Multiple mechanisms of rottlerin toxicity in A375 melanoma cells. Biofactors 2019; 45(6): 920-9.
[http://dx.doi.org/10.1002/biof.1551] [PMID: 31408224]
[38]
Daveri E, Valacchi G, Romagnoli R, Maellaro E, Maioli E. Antiproliferative effect of rottlerin on Sk-Mel-28 melanoma cells. Evidbased compl altern med 2015; 2015: 545838.
[http://dx.doi.org/10.1155/2015/545838]
[39]
Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin 2018; 68(4): 284-96.
[http://dx.doi.org/10.3322/caac.21456] [PMID: 29809280]
[40]
Stewart C, Ralyea C, Lockwood S. Ovarian cancer: An integrated review. Semin Oncol Nurs 2019; 35(2): 151-6.
[http://dx.doi.org/10.1016/j.soncn.2019.02.001] [PMID: 30867104]
[41]
Nebgen DR, Lu KH, Bast RC Jr. Novel approaches to ovarian cancer screening. Curr Oncol Rep 2019; 21(8): 75.
[http://dx.doi.org/10.1007/s11912-019-0816-0] [PMID: 31346778]
[42]
Prudnikova TY, Chernoff J. The Group I Pak inhibitor Frax-1036 sensitizes 11q13-amplified ovarian cancer cells to the cytotoxic effects of Rottlerin. Small GTPases 2017; 8(4): 193-8.
[http://dx.doi.org/10.1080/21541248.2016.1213089] [PMID: 27427770]
[43]
Tsitlakidis A, Aifantis EC, Kritis A, et al. Mechanical properties of human glioma. Neurol Res 2020; 42(12): 1018-26.
[http://dx.doi.org/10.1080/01616412.2020.1796381] [PMID: 32705967]
[44]
Jane EP, Premkumar DR, Pollack IF. Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J Pharmacol Exp Ther 2006; 319(3): 1070-80.
[http://dx.doi.org/10.1124/jpet.106.108621] [PMID: 16959960]
[45]
Wang L, Hou Y, Yin X, et al. Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells. Oncotarget 2016; 7(43): 69770-82.
[http://dx.doi.org/10.18632/oncotarget.11974] [PMID: 27626499]
[46]
Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet 2019; 394(10192): 64-80.
[http://dx.doi.org/10.1016/S0140-6736(19)30956-0] [PMID: 31178151]
[47]
Hou Y, Feng S, Wang L, et al. Inhibition of Notch-1 pathway is involved in rottlerin-induced tumor suppressive function in nasopharyngeal carcinoma cells. Oncotarget 2017; 8(37): 62120-30.
[http://dx.doi.org/10.18632/oncotarget.19097] [PMID: 28977931]
[48]
Evison M. The current treatment landscape in the UK for stage III NSCLC. Br J Cancer 2020; 123 (S1)(1): 3-9.
[http://dx.doi.org/10.1038/s41416-020-01069-z] [PMID: 33293670]
[49]
Alexander M, Kim SY, Cheng H. Update 2020: Management of non-small cell lung cancer. Lung 2020; 198(6): 897-907.
[http://dx.doi.org/10.1007/s00408-020-00407-5] [PMID: 33175991]
[50]
Osmani L, Askin F, Gabrielson E, Li QK. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. Semin Cancer Biol 2018; 52(Pt 1): 103-9.
[http://dx.doi.org/10.1016/j.semcancer.2017.11.019] [PMID: 29183778]
[51]
Zhao Z, Zheng N, Wang L, Hou Y, Zhou X, Wang Z. Rottlerin exhibits antitumor activity via down-regulation of TAZ in non-small cell lung cancer. Oncotarget 2017; 8(5): 7827-38.
[http://dx.doi.org/10.18632/oncotarget.13974] [PMID: 27999199]
[52]
Torphy RJ, Fujiwara Y, Schulick RD. Pancreatic cancer treatment: Better, but a long way to go. Surg Today 2020; 50(10): 1117-25.
[http://dx.doi.org/10.1007/s00595-020-02028-0] [PMID: 32474642]
[53]
Zhao Z, Liu W. Pancreatic cancer: A review of risk factors, diagnosis, and treatment. Technol Cancer Res Treat 2020; 19: 1533033820962117.
[http://dx.doi.org/10.1177/1533033820962117] [PMID: 33357065]
[54]
Ohno I, Eibl G, Odinokova I, et al. Rottlerin stimulates apoptosis in pancreatic cancer cells through interactions with proteins of the Bcl-2 family. Am J Physiol Gastrointest Liver Physiol 2010; 298(1): G63-73.
[http://dx.doi.org/10.1152/ajpgi.00257.2009] [PMID: 19762431]
[55]
Su J, Wang L, Yin X, et al. Rottlerin exhibits anti-cancer effect through inactivation of S phase kinase-associated protein 2 in pancreatic cancer cells. Am J Cancer Res 2016; 6(10): 2178-91.
[PMID: 27822410]
[56]
Carlsson SV, Vickers AJ. Screening for prostate cancer. Med Clin North Am 2020; 104(6): 1051-62.
[http://dx.doi.org/10.1016/j.mcna.2020.08.007] [PMID: 33099450]
[57]
Siegel DA, O’Neil ME, Richards TB, Dowling NF, Weir HK. Prostate cancer incidence and survival, by stage and race/ethnicity — united States, 2001–2017. MMWR Morb Mortal Wkly Rep 2020; 69(41): 1473-80.
[http://dx.doi.org/10.15585/mmwr.mm6941a1] [PMID: 33056955]
[58]
Cieslikowski WA, Haber T, Krajnak S, et al. Co-administration of tyrosine kinase inhibitors with rottlerin in metastatic prostate cancer cells. EXCLI J 2021; 20: 1585-96.
[PMID: 34924906]
[59]
Zheng N, Wang L, Hou Y, Zhou X, He Y, Wang Z. Rottlerin inhibits cell growth and invasion via down-regulation of EZH2 in prostate cancer. Cell Cycle 2018; 17(21-22): 2460-73.
[http://dx.doi.org/10.1080/15384101.2018.1542897] [PMID: 30394832]
[60]
Kumar D, Shankar S, Srivastava RK. Rottlerin induces autophagy and apoptosis in prostate cancer stem cells via PI3K/Akt/mTOR signaling pathway. Cancer Lett 2014; 343(2): 179-89.
[http://dx.doi.org/10.1016/j.canlet.2013.10.003] [PMID: 24125861]
[61]
Richters A, Aben KKH, Kiemeney LALM. The global burden of urinary bladder cancer: An update. World J Urol 2020; 38(8): 1895-904.
[http://dx.doi.org/10.1007/s00345-019-02984-4] [PMID: 31676912]
[62]
Golijanin DJ, Kakiashvili D, Madeb RR, Messing EM, Lerner SP. Chemoprevention of bladder cancer. World J Urol 2006; 24(5): 445-72.
[http://dx.doi.org/10.1007/s00345-006-0123-x] [PMID: 17048030]
[63]
Patel VG, Oh WK, Galsky MD. Treatment of muscle-invasive and advanced bladder cancer in 2020. CA Cancer J Clin 2020; 70(5): 404-23.
[http://dx.doi.org/10.3322/caac.21631] [PMID: 32767764]
[64]
Kuan JW, Su AT, Leong CF, Osato M, Sashida G. Systematic review of pre-clinical chronic myeloid leukaemia. Int J Hematol 2018; 108(5): 465-84.
[http://dx.doi.org/10.1007/s12185-018-2528-x] [PMID: 30218276]
[65]
Houshmand M, Simonetti G, Circosta P, et al. Chronic myeloid leukemia stem cells. Leukemia 2019; 33(7): 1543-56.
[http://dx.doi.org/10.1038/s41375-019-0490-0] [PMID: 31127148]
[66]
Ren R. Mechanisms of BCR–ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer 2005; 5(3): 172-83.
[http://dx.doi.org/10.1038/nrc1567] [PMID: 15719031]
[67]
Kurosu T, Tsuji K, Kida A, Koyama T, Yamamoto M, Miura O. Rottlerin synergistically enhances imatinib-induced apoptosis of BCR/ABL-expressing cells through its mitochondrial uncoupling effect independent of protein kinase C-δ. Oncogene 2007; 26(21): 2975-87.
[http://dx.doi.org/10.1038/sj.onc.1210117] [PMID: 17130834]
[68]
Seib CD, Sosa JA. Evolving understanding of the epidemiology of thyroid cancer. Endocrinol Metab Clin North Am 2019; 48(1): 23-35.
[http://dx.doi.org/10.1016/j.ecl.2018.10.002] [PMID: 30717905]
[69]
Kilfoy BA, Zheng T, Holford TR, et al. International patterns and trends in thyroid cancer incidence, 1973–2002. Cancer Causes Control 2009; 20(5): 525-31.
[http://dx.doi.org/10.1007/s10552-008-9260-4] [PMID: 19016336]
[70]
Araque KA, Gubbi S, Klubo-Gwiezdzinska J. Updates on the management of thyroid cancer. Horm Metab Res 2020; 52(8): 562-77.
[http://dx.doi.org/10.1055/a-1089-7870]
[71]
Lin CJ, Lin CY, Chen Y, Huang SH, Wang SM. Rottlerin inhibits migration of follicular thyroid carcinoma cells by PKCdeltaindependent destabilization of the focal adhesion complex. J Cell Biochem 2010; 110(2): 428-37.
[PMID: 20225271]
[72]
Kamiya K, Kishimoto M, Sugai J, Komine M, Ohtsuki M. Risk factors for the development of psoriasis. Int J Mol Sci 2019; 20(18): 4347.
[http://dx.doi.org/10.3390/ijms20184347] [PMID: 31491865]
[73]
Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker JNWN. Psoriasis. Lancet 2021; 397(10281): 1301-15.
[http://dx.doi.org/10.1016/S0140-6736(20)32549-6] [PMID: 33812489]
[74]
Maioli E, Valacchi G. Rottlerin: Bases for a possible usage in psoriasis. Curr Drug Metab 2010; 11(5): 425-30.
[http://dx.doi.org/10.2174/138920010791526097] [PMID: 20540694]
[75]
Lama Z, Gaudin Y, Blondel D, Lagaudrière-Gesbert C. Kinase inhibitors tyrphostin 9 and rottlerin block early steps of rabies virus cycle. Antiviral Res 2019; 168: 51-60.
[http://dx.doi.org/10.1016/j.antiviral.2019.04.014] [PMID: 31071352]

Rights & Permissions Print Cite
Article Metrics
11
2
© 2024 Bentham Science Publishers | Privacy Policy