Skip to content
2000
image of Integrative Bioinformatics and Experimental Validation Reveal the Mechanistic Action of Patchouli Alcohol in Prostate Cancer Treatment

Abstract

Introduction

Prostate cancer is an androgen-dependent malignancy, and the use of androgen deprivation therapies frequently results in treatment resistance, relapse, and the development of aggressive castration-resistant tumors. Patchouli alcohol, a tricyclic sesquiterpene derived from Pogostemon cablin of the Labiatae family, has demonstrated potential in modulating inflammatory responses and tumor progression. This study aimed to investigate the mechanisms through which patchouli alcohol influences inflammatory pathways associated with prostate cancer using bioinformatics and experimental validation.

Methods

Differentially Expressed Genes (DEGs) were identified from the GSE46602 dataset, containing 36 prostate cancer and 14 normal prostate biopsy samples, using the GEO2R tool (adjusted P < 0.05). Functional annotation was performed using GO and KEGG databases, while PPI networks were constructed STRING and Cytoscape. Key hub genes were identified. To validate the bioinformatics findings, qPCR and Western blotting were employed to confirm the differential expression of selected hub genes in DU145 prostate cancer cells treated with patchouli oil.

Results

Bioinformatic analysis revealed 71 DEGs, including 35 upregulated and 36 downregulated genes. Thirteen hub genes were identified (DCK, APRT, ADK, KCNK9, ADSL, PKM, KCNK3, S100A10, ENTPD2, PKLR, ARHGEF38, TPK1, and AK5), which were enriched in pathways, such as MAPK, PI3K-Akt, Ras, and Rap1. Experimental validation confirmed the upregulation of DCK, APRT, KCNK9, ADSL, PKM, S100A10, ENTPD2, PKLR, ARHGEF38, and AK5, and the downregulation of ADK, KCNK3, and TPK1 at both the mRNA and protein levels.

Conclusion

Patchouli alcohol appears to influence multiple hub genes associated with prostate cancer progression through its modulation of key cellular signaling and metabolic pathways. These findings support its potential role as a therapeutic agent for prostate cancer.

Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010355513241224101450
2025-01-22
2025-03-26
Loading full text...

Full text loading...

References

  1. Ma L. He H. Jiang K. Jiang P. He H. Feng S. Chen K. Shao J. Deng G. FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer. Aging 2020 12 7 6352 6369 10.18632/aging.103030 32283544
    [Google Scholar]
  2. Berlin A. Fernández M.I. Advances in the treatment of castration-resistant prostate cancer: Emphasis in new hormonal therapies. Rev. Med. Chil. 2015 143 2 223 236 10.4067/S0034‑98872015000200010 25860365
    [Google Scholar]
  3. Lee D.J. Cha E.K. Dubin J.M. Beltran H. Chromecki T.F. Fajkovic H. Scherr D.S. Tagawa S.T. Shariat S.F. Novel therapeutics for the management of castration‐resistant prostate cancer (CRPC). BJU Int. 2012 109 7 968 985 10.1111/j.1464‑410X.2011.10643.x 22035221
    [Google Scholar]
  4. Li J. Tian Y. Zhao L. Wang Y. Zhang H. Xu D. Zhao X. Li Y. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells. Asian J. Androl. 2016 18 4 607 612 10.4103/1008‑682X.169997 26698234
    [Google Scholar]
  5. van Beek T.A. Joulain D. The essential oil of patchouli, Pogostemon cablin : A review. Flavour Fragrance J. 2018 33 1 6 51 10.1002/ffj.3418
    [Google Scholar]
  6. Yingngam B. Chemistry of Essential Oils. Flavors and Fragrances in Food Processing: Preparation and Characterization Methods. American Chemical Society 2022 189 223
    [Google Scholar]
  7. Jeong J.B. Choi J. Lou Z. Jiang X. Lee S.H. Patchouli alcohol, an essential oil of Pogostemon cablin, exhibits anti-tumorigenic activity in human colorectal cancer cells. Int. Immunopharmacol. 2013 16 2 184 190 10.1016/j.intimp.2013.04.006 23602914
    [Google Scholar]
  8. Zheng Y.F. Xie J.H. Xu Y.F. Liang Y.Z. Mo Z.Z. Jiang W.W. Chen X.Y. Liu Y.H. Yu X.D. Huang P. Su Z.R. Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats. Chem. Biol. Interact. 2014 222 27 36 10.1016/j.cbi.2014.08.008 25168850
    [Google Scholar]
  9. Yu X.D. Xie J.H. Wang Y.H. Li Y.C. Mo Z.Z. Zheng Y.F. Su J.Y. Liang Y. Liang J.Z. Su Z.R. Huang P. Selective antibacterial activity of patchouli alcohol against Helicobacter pylori based on inhibition of urease. Phytother. Res. 2015 29 1 67 72 10.1002/ptr.5227 25243578
    [Google Scholar]
  10. Lu X. Yang L. Lu C. Xu Z. Qiu H. Wu J. Wang J. Tong J. Zhu Y. Shen J. Molecular role of EGFR-MAPK pathway in patchouli alcohol-induced apoptosis and cell cycle arrest on A549 cells in vitro and in vivo. BioMed Res. Int. 2016 2016 1 12 10.1155/2016/4567580 27830146
    [Google Scholar]
  11. Song Y. Chang L. Wang X. Tan B. Li J. Zhang J. Zhang F. Zhao L. Liu G. Huo B. Regulatory mechanism and experimental verification of patchouli alcohol on gastric cancer cell based on network pharmacology. Front. Oncol. 2021 11 711984 10.3389/fonc.2021.711984 34540679
    [Google Scholar]
  12. Cai J. Zhao J. Gao P. Xia Y. Patchouli alcohol suppresses castration-resistant prostate cancer progression by inhibiting NF-κB signal pathways. Transl. Androl. Urol. 2022 11 4 528 542 10.21037/tau‑22‑220 35558260
    [Google Scholar]
  13. Wang H. Guo M. Wei H. Chen Y. Targeting MCL-1 in cancer: Current status and perspectives. J. Hematol. Oncol. 2021 14 1 67 10.1186/s13045‑021‑01079‑1 33883020
    [Google Scholar]
  14. Pathria P. Louis T.L. Varner J.A. Targeting tumor-associated macrophages in cancer. Trends Immunol. 2019 40 4 310 327 10.1016/j.it.2019.02.003 30890304
    [Google Scholar]
  15. Günther J Seyfert HM The first line of defence: Insights into mechanisms and relevance of phagocytosis in epithelial cells. Semin. Immunopathol. 2018 40 6 555 565 10.1007/s00281‑018‑0701‑1 30182191
    [Google Scholar]
  16. Crorkin P. Hao S. Ferreri N.R. Responses to Ang II (angiotensin II), salt intake, and lipopolysaccharide reveal the diverse actions of TNF-α (tumor necrosis factor-α) on blood pressure and renal function. Hypertension 2022 79 12 2656 2670 10.1161/HYPERTENSIONAHA.122.19464 36129177
    [Google Scholar]
  17. Dovey Z.S. Nair S.S. Chakravarty D. Tewari A.K. Racial disparity in prostate cancer in the African American population with actionable ideas and novel immunotherapies. Cancer Rep. 2021 4 5 e1340 10.1002/cnr2.1340 33599076
    [Google Scholar]
  18. Hassan B. Akcakanat A. Holder A.M. Meric-Bernstam F. Targeting the PI3-kinase/Akt/mTOR signaling pathway. Surg. Oncol. Clin. N. Am. 2013 22 4 641 664 10.1016/j.soc.2013.06.008 24012393
    [Google Scholar]
  19. Spirina L.V. Kovaleva I.V. Usynin E.A. Goorbunov A.K. Kondakova I.V. Progesterone receptor expression in the benign prostatic hyperplasia and prostate cancer tissues, relation with transcription, growth factors, hormone reception and components of the AKT/mTOR signaling pathway. Asian Pac. J. Cancer Prev. 2020 21 2 423 429 10.31557/APJCP.2020.21.2.423 32102520
    [Google Scholar]
  20. Roy S.K. Srivastava R.K. Shankar S. Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J. Mol. Signal. 2010 5 1 10 10.1186/1750‑2187‑5‑10 20642839
    [Google Scholar]
  21. Xing Y. Li A. Yang Y. Li X. Zhang L. Guo H. The regulation of FOXO1 and its role in disease progression. Life Sci. 2018 193 124 131 10.1016/j.lfs.2017.11.030 29158051
    [Google Scholar]
  22. Mohd Yusof YA Gingerol and its role in chronic diseases. Adv. Exp. Med. Biol. 2016 929 177 207 10.1007/978‑3‑319‑41342‑6_8 27771925
    [Google Scholar]
  23. Pan C.W. Jin X. Zhao Y. Pan Y. Yang J. Karnes R.J. Zhang J. Wang L. Huang H. AKT ‐phosphorylated FOXO 1 suppresses ERK activation and chemoresistance by disrupting IQGAP 1‐ MAPK interaction. EMBO J. 2017 36 8 995 1010 10.15252/embj.201695534 28279977
    [Google Scholar]
  24. Xie L. Guo Y. Chen Y. Zhang L. Wang Z. Zhang T. Wang B. A potential drug combination of omeprazole and patchouli alcohol significantly normalizes oxidative stress and inflammatory responses against gastric ulcer in ethanol-induced rat model. Int. Immunopharmacol. 2020 85 106660 10.1016/j.intimp.2020.106660 32559721
    [Google Scholar]
  25. Hu G Peng C Xie X Zhang S Cao X Availability, pharmaceutics, security, pharmacokinetics, and pharmacological activities of patchouli alcohol. Evid. Based Complement Alternat. Med. 2017 2017 4850612 10.1155/2017/4850612 28421121
    [Google Scholar]
  26. Yang L. Chen H. Li R. Li H. Rui X. Zhou L. Liu N. Ji Q. Li Q. Mufangji decoction and its active ingredient patchouli alcohol inhibit tumor growth through regulating Akt/mTOR-mediated autophagy in nonsmall-cell lung cancer. Evid. Based Complement. Alternat. Med. 2021 2021 1 11 10.1155/2021/2373865 34764997
    [Google Scholar]
  27. Wei L. Chen Y. Yu Q.Y. Wang Y. Liu G. Patchouli alcohol protects against ischemia/reperfusion-induced brain injury via inhibiting neuroinflammation in normal and obese mice. Brain Res. 2018 1682 61 70 10.1016/j.brainres.2017.12.039 29291393
    [Google Scholar]
  28. Chang K.F. Lai H.C. Lee S.C. Huang X.F. Huang Y.C. Chou T.E. Hsiao C.Y. Tsai N.M. The effects of patchouli alcohol and combination with cisplatin on proliferation, apoptosis and migration in B16F10 melanoma cells. J. Cell. Mol. Med. 2023 27 10 1423 1435 10.1111/jcmm.17745 37038620
    [Google Scholar]
  29. Lee H.S. Lee J. Smolensky D. Lee S.H. Potential benefits of patchouli alcohol in prevention of human diseases: A mechanistic review. Int. Immunopharmacol. 2020 89 Pt A 107056 10.1016/j.intimp.2020.107056 33039955
    [Google Scholar]
  30. Shah S Brock EJ Ji K Mattingly RR Ras and Rap1: A tale of two GTPases. Semin. Canc. Biol. 2019 54 29 39 10.1016/j.semcancer.2018.03.005 29621614
    [Google Scholar]
  31. Yi-Lei Z. Yi-Lei Z. Ruo-Chen W. Ken C. Brian Z R. Li S. Ruo-Chen W. Ken C. Brian Z R. Li S. Roles of Rap1 signaling in tumor cell migration and invasion. Cancer Biol. Med. 2017 14 1 90 99 10.20892/j.issn.2095‑3941.2016.0086 28443208
    [Google Scholar]
  32. Song J. Chen W. Zhu G. Wang W. Sun F. Zhu J. Immunogenomic profiling and classification of prostate cancer based on HIF-1 signaling pathway. Front. Oncol. 2020 10 1374 10.3389/fonc.2020.01374 32850440
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010355513241224101450
Loading
/content/journals/cpb/10.2174/0113892010355513241224101450
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test