Skip to main content
SpringerLink
Log in

Organosulfur Compound Identified from Striga angustifolia (D. Don) C.J. Saldanha Inhibits Lung Cancer Growth and Induces Apoptosis via p53/mTOR Signaling Pathway

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

The Striga angustifolia (D. Don) C.J. Saldanha was used as an Ayurvedic and homeopathic medicine for cancer by the tribal peoples of the Maruthamalai Hills, Coimbatore, India. Hence, the traditional use that has been proven to be effective lacks convincing scientific references. This present study was conducted to investigate the presence of potentially bioactive compounds from S. angustifolia and provides a scientific basis for the ethnobotanical utility. The organosulfur compound 5,5′-dithiobis(1-phenyl-1H-tetrazole) (COMP1) was isolated from S. angustifolia extracts, and the structures of COMP1 were elucidated and characterized by using 13C and 1H nuclear magnetic resonance (NMR) and single crystal X-ray powder diffraction (XRD). Our findings showed that COMP1 significantly reduced cell proliferation of breast and lung cancer cells, but not that of non-malignant epithelial cells. Further analysis revealed that COMP1 promoted cell cycle arrest and apoptosis of lung cancer cells. Mechanistically, COMP1 facilitates p53 activity and inhibits mammalian target of rapamycin (mTOR) signaling, thereby inducing cell cycle arrest and apoptosis of lung cancer cells by inhibiting cell growth. Our findings suggest that COMP1 may serve as a potential drug for lung cancer through the regulation of p53/mTOR pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
Fig. 8.

Similar content being viewed by others

Abbreviations

(AO/EB):

Dual acridine orange/ethidium bromide

COMP1:

5,5′-Dithiobis(1-phenyl-1H-tetrazole)

DAPI:

4′,6-Diamidino-2-phenylindole

DFT:

Density functional theory

HOMO:

Highest Occupied Molecular Orbital

DMSO:

Dimethyl sulfoxide

FT-IR:

Fourier-transform infrared spectroscopy

LUMO:

Lowest Unoccupied Molecular Orbital

mTOR:

Mammalian target of rapamycin

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NMR:

Nuclear magnetic resonance

TLC:

Thin-layer chromatography

UV:

Visible spectroscopy-ultraviolet-visible spectroscopy

WHO:

World Health Organization

XRD:

X-ray crystallography

References

  1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71, 209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. WHO. (2019). Global action plan on physical activity 2018-2030: More active people for a healthier world.ed. World Health Organization.

    Google Scholar 

  3. Luo, L. X., Li, Y., Liu, Z. Q., Fan, X. X., Duan, F. G., Li, R. Z., Yao, X. J., Leung, E. L. H., & Liu, L. (2017). Honokiol induces apoptosis, G1 arrest, and autophagy in KRAS mutant lung cancer cells. Frontiers in Pharmacology, 8, 199. https://doi.org/10.3389/fphar.2017.00199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. An, H. K., Kim, K. S., Lee, J. W., Park, M. H., Moon, H. I., Park, S. J., Baik, J. S., Kim, C. H., & Lee, Y. C. (2014). Mimulone-induced autophagy through p53-mediated AMPK/mTOR pathway increases caspase-mediated apoptotic cell death in A549 human lung cancer cells. PLoS One, 9, e114607. https://doi.org/10.1371/journal.pone.0114607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dehelean, C. A., Marcovici, I., Soica, C., Mioc, M., Coricovac, D., Iurciuc, S., Cretu, O. M., & Pinzaru, I. (2021). Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules, 26, 1109. https://doi.org/10.3390/molecules26041109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Elmore, S. (2007). Apoptosis: a review of programmed cell death. Toxicologic pathology, 35, 495–516. https://doi.org/10.1080/01926230701320337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. McBride, O., Merry, D., & Givol, D. (1986). The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13). Proceedings of the National Academy of Sciences, 83, 130–134. https://doi.org/10.1073/pnas.83.1.130

    Article  CAS  Google Scholar 

  8. Lin, T., Hou, P.-F., Meng, S., Chen, F., Jiang, T., Li, M.-L., Shi, M.-L., Liu, J.-J., Zheng, J.-N., & Bai, J. (2019). Emerging roles of p53 related lncRNAs in cancer progression: A systematic review. International Journal of Biological Sciences, 15, 1287. https://doi.org/10.7150/ijbs.33218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen, J. (2016). The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harbor Perspectives in Medicine, 6, a026104. https://doi.org/10.1101/cshperspect.a026104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ozaki, T., & Nakagawara, A. (2011). Role of p53 in cell death and human cancers. Cancers, 3, 994–1013. https://doi.org/10.3390/cancers3010994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang, F., Mayca Pozo, F., Tian, D., Geng, X., Yao, X., Zhang, Y., & Tang, J. (2020). Shikonin inhibits cancer through P21 upregulation and apoptosis induction. Frontiers in Pharmacology, 11, 861. https://doi.org/10.3389/fphar.2020.00861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W., Fong, H. H., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., Moon, R. C., & Pezzuto, J. M. (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 275(5297), 218–220. https://doi.org/10.1126/science.275.5297.218

    Article  CAS  PubMed  Google Scholar 

  13. Wang, J., Li, J., Cao, N., Li, Z., Han, J., & Li, L. (2018). Resveratrol, an activator of SIRT1, induces protective autophagy in non-small-cell lung cancer via inhibiting Akt/mTOR and activating p38-MAPK. OncoTargets and Therapy, 11, 7777–7786. https://doi.org/10.2147/OTT.S159095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Suppipat, K., Park, C. S., Shen, Y., Zhu, X., & Lacorazza, H. D. (2012). Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells. PloS One, 7(12), e51251. https://doi.org/10.1371/journal.pone.0051251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lubecka-Pietruszewska, K., Kaufman-Szymczyk, A., Stefanska, B., Cebula-Obrzut, B., Smolewski, P., & Fabianowska-Majewska, K. (2015). Sulforaphane alone and in combination with clofarabine epigenetically regulates the expression of DNA methylation-silenced tumour suppressor genes in human breast cancer cells. Journal of Nutrigenetics and Nutrigenomics, 8(2), 91–101. https://doi.org/10.1159/000439111

    Article  CAS  PubMed  Google Scholar 

  16. Kan, S. F., Wang, J., & Sun, G. X. (2018). Sulforaphane regulates apoptosis- and proliferation-related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer. International Journal of Molecular Medicine, 42(5), 2447–2458. https://doi.org/10.3892/ijmm.2018.3860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vignesh, A., Sivalingam, R., Selvakumar, S., & Vasanth, K. (2022). A review on ethnomedicinal and phytopharmacological potential of traditionally wild and endemic plant Berberis tinctoria Lesch. Thai Journal of Pharmaceutical Sciences, 46, 137–148.

    CAS  Google Scholar 

  18. Ray, R., & Ray, A. (2020). Medicinal practices of sacred natural site: A socio-religious approach for successful implementation of primary healthcare services. Ethnobotany Research and Applications, 20, 1–46. https://doi.org/10.32859/era.20.34.1-46

    Article  Google Scholar 

  19. Quattrocchi, U. (2012). CRC world dictionary of medicinal and poisonous plants: common names, scientific names, eponyms, synonyms, and etymology (5 Volume Set) (p. 3960). CRC press.

    Google Scholar 

  20. Mahendru, N., Masresha, M., Joshi, P., Marndi, S., & Kumar, S. (2022). Medicinally important terrestrial parasitic plants. Medico-Biowealth of India, 5, 52–57. https://doi.org/10.5281/zenodo.5976089

    Article  Google Scholar 

  21. O’Neill, A. R., & Rana, S. K. (2016). An ethnobotanical analysis of parasitic plants (Parijibi) in the Nepal Himalaya. Journal of Ethnobiology and Ethnomedicine, 12, 1–15. https://doi.org/10.1186/s13002-016-0086-y

    Article  Google Scholar 

  22. Santhoshkumar, S., Nagarajan, N., & Santhoshkumar, K. (2018). Studies on the arbuscular mycorrhizal fungal biodiversity in the plant species of Kondranghi hills, Dindugul district, Tamil Nadu, India. Kongunadu Research Journal, 5, 34–40. https://doi.org/10.26524/krj268

    Article  Google Scholar 

  23. Raja, K., Selvakumar, S., Rakkiyappan, R., Veerakumari, K. P., & Vasanth, K. (2021). Anti-proliferative phytoconstituents from Striga angustifolia (D. Don) CJ Saldanha–An in vitro and in silico approach. Phytomedicine Plus, 1, 100062. https://doi.org/10.1016/j.phyplu.2021.100062

    Article  Google Scholar 

  24. Mindidiba, J. B., Tangbadioa, H. C., Aminata, P. N., Abdoulaye, S., Emmanuel, A. T., & Georges, A. O. (2022). Antitumoral effect of Striga hermonthica (Delile) Benth. methanolic extract is mediated by alterations on procaspase-3 and cyclin B expression in prostate cancer cell lines. Journal of Pharmacognosy and Phytotherapy, 14, 1–7. https://doi.org/10.5897/JPP2022.0619

    Article  Google Scholar 

  25. Lawan, M., & Mai Garba, I. (2021). Medicinal value of some bioactive compounds from three species of Striga grass (S. hermontheca, S. aciatica and S. gesnerioides) extractions. Advanced Journal of Chemistry-Section A, 4, 308–316. https://doi.org/10.22034/AJCA.2022.335594.1307

    Article  CAS  Google Scholar 

  26. Raja, K., Balamurugan, V., Selvakumar, S., & Vasanth, K. (2022). Striga angustifolia mediated synthesis of silver nanoparticles: Anti-microbial, antioxidant and anti-proliferative activity in apoptotic p53 signalling pathway. Journal of Drug Delivery Science and Technology, 67, 102945. https://doi.org/10.1016/j.jddst.2021.102945

    Article  CAS  Google Scholar 

  27. Vignesh, A., Pradeepa Veerakumari, K., Selvakumar, S., Rakkiyappan, R., & Vasanth, K. (2021). Nutritional assessment, antioxidant, anti-inflammatory and antidiabetic potential of traditionally used wild plant, Berberis tinctoria Lesch. Trends in Phytochemical Research, 5, 71–92. https://doi.org/10.30495/TPR.2021.1914719.1186

    Article  CAS  Google Scholar 

  28. Vusak, V., Vusak, D., Molcanov, K., & Ernest, M. (2020). Synthesis, crystal structure and spectroscopic and Hirshfeld surface analysis of 4-hydroxy-3-methoxy-5-nitrobenzaldehyde. Acta Crystallographica Section E: Crystallographic Communications, 76, 239–244. https://doi.org/10.1107/S2056989020000225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Caricato, M., Frisch, M. J., Hiscocks, J., & Frisch, M. J. (2009). Gaussian 09: IOps Reference. Citeseer. Gaussian, Inc ISBN: 978-1-935522-02-7.

    Google Scholar 

  30. Chibani, S., Laurent, A. D., Le Guennic, B., & Jacquemin, D. (2014). Improving the accuracy of excited-state simulations of BODIPY and Aza-BODIPY dyes with a joint SOS-CIS (D) and TD-DFT approach. Journal of Chemical Theory and Computation, 10, 4574–4582. https://doi.org/10.1021/ct500655k

    Article  CAS  PubMed  Google Scholar 

  31. Ali, M., Mansha, A., Asim, S., Zahid, M., Usman, M., & Ali, N. (2018). DFT study for the spectroscopic and structural analysis of p-dimethylaminoazobenzene. Journal of Spectroscopy, 2018, 1–15. https://doi.org/10.1155/2018/9365153

    Article  CAS  Google Scholar 

  32. Elshakre, M., & Sadiek, I. (2016). A DFT study of the dissociation, ionization, and UV/visible spectra of methyl hypobromite. Computational and Theoretical Chemistry, 1088, 32–43. https://doi.org/10.1016/j.comptc.2016.04.028

    Article  CAS  Google Scholar 

  33. Deckert-Gaudig, T., Taguchi, A., Kawata, S., & Deckert, V. (2017). Tip-enhanced Raman spectroscopy–from early developments to recent advances. Chemical Society Reviews, 46, 4077–4110. https://doi.org/10.1039/C7CS00209B

    Article  CAS  PubMed  Google Scholar 

  34. Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry, 19, 1639–1662. https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14%3C1639::AID-JCC10%3E3.0.CO;2-B

    Article  CAS  Google Scholar 

  35. Vignesh, A., Selvakumar, S., & Vasanth, K. (2021). Green synthesis and characterization of zinc oxide nanoparticles using Berberis tinctoria Lesch. leaves and fruits extract of multi-biological applications. Nanomedicine Research Journal, 6, 128–147. https://doi.org/10.22034/nmrj.2021.02.005

    Article  CAS  Google Scholar 

  36. Sasidharan, S., Chen, Y., Saravanan, D., Sundram, K., & Latha, L. Y. (2011). Extraction, isolation and characterization of bioactive compounds from plants’ extracts. African Journal of Traditional, Complementary and Alternative Medicines, 8, 1–10. https://doi.org/10.4314/ajtcam.v8i1.60483

    Article  CAS  Google Scholar 

  37. Kazmi, F., Yerino, P., McCoy, C., Parkinson, A., Buckley, D. B., & Ogilvie, B. W. (2018). An assessment of the in vitro inhibition of cytochrome P450 enzymes, UDP-glucuronosyltransferases, and transporters by phosphodiester-or phosphorothioate-linked oligonucleotides. Drug Metabolism and Disposition, 46, 1066–1074. https://doi.org/10.1124/dmd.118.081729

    Article  CAS  PubMed  Google Scholar 

  38. Prati, S., Joseph, E., Sciutto, G., & Mazzeo, R. (2010). New advances in the application of FTIR microscopy and spectroscopy for the characterization of artistic materials. Accounts of Chemical Research, 43, 792–801. https://doi.org/10.1021/ar900274f

    Article  CAS  PubMed  Google Scholar 

  39. Prabhakaran, R., Geetha, A., Thilagavathi, M., Karvembu, R., Krishnan, V., Bertagnolli, H., & Natarajan, K. (2004). Synthesis, characterization, EXAFS investigation and antibacterial activities of new ruthenium (III) complexes containing tetradentate Schiff base. Journal of Inorganic Biochemistry, 98, 2131–2140. https://doi.org/10.1016/j.jinorgbio.2004.09.020

    Article  CAS  PubMed  Google Scholar 

  40. Rammohan, A., Bhaskar, B. V., Camilo, A., Jr., Gunasekar, D., Gu, W., & Zyryanov, G. V. (2020). In silico, in vitro antioxidant and density functional theory based structure activity relationship studies of plant polyphenolics as prominent natural antioxidants. Arabian Journal of Chemistry, 13, 3690–3701. https://doi.org/10.1016/j.arabjc.2019.12.017

    Article  CAS  Google Scholar 

  41. Ermiş, E., Durmuş, K., Aygüzer, Ö. U., Berber, H., & Güllü, M. (2018). A new 2, 2′-oxydianiline derivative symmetrical azomethine compound containing thiophene units: Synthesis, spectroscopic characterization (UV–Vis, FTIR, 1H and 13C NMR) and DFT calculations. Journal of Molecular Structure, 1168, 115–126. https://doi.org/10.1016/j.molstruc.2018.05.021

    Article  CAS  Google Scholar 

  42. Gillet, J.-P., Varma, S., & Gottesman, M. M. (2013). The clinical relevance of cancer cell lines. Journal of the National Cancer Institute, 105, 452–458. https://doi.org/10.1093/jnci/djt007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Spector, M., Goldman, R. D., & Leinwand, L. A. (1998). Cells. A Laboratory Manual, 4.1–4.7. Cold Spring Harbor Laboratory Press.

    Google Scholar 

  44. Liu, M.-C., Yang, S.-J., Jin, L.-H., Hu, D.-Y., Xue, W., Song, B.-A., & Yang, S. (2012). Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety. European Journal of Medicinal Chemistry, 58, 128–135. https://doi.org/10.1016/j.ejmech.2012.08.048

    Article  CAS  PubMed  Google Scholar 

  45. Borrero, L. J. H., & El-Deiry, W. S. (2021). Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1876, 188556. https://doi.org/10.1016/j.bbcan.2021.188556

    Article  CAS  Google Scholar 

Download references

Availability of Data and Materials

All data generated or analyzed during this study are included in this published article.

Funding

The present study was supported by RUSA 2.0. BEICH (Ref. No: IQAC/RUSA 2.0/PF/2020/dated: 03/02/2020).

Author information

Authors and Affiliations

  1. Department of Botany, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India

    Kannan Raja, Arumugam Vignesh & Krishnan Vasanth

  2. Department of Biochemistry, Guindy Campus, University of Madras, Chennai, 600025, India

    Ponnusamy Lavanya & Manoharan Ravi

  3. Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India

    Subramaniam Selvakumar

Authors
  1. Kannan Raja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arumugam Vignesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ponnusamy Lavanya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manoharan Ravi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Subramaniam Selvakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Krishnan Vasanth
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Kannan Raja, Arumugam Vignesh, and Ponnusamy Lavanya: Conceptualization, data curation, methodology, investigation and writing—original draft. Manoharan Ravi and Subramaniam Selvakumar: Formal analysis, writing—review and editing and validation. Krishnan Vasanth: Project administration, writing—review and editing and supervision reviewing and editing the manuscript. All the data were generated in house, and no paper mill was used. All the authors agree to be accountable for all aspects of work ensuring integrity and accuracy.

Corresponding author

Correspondence to Krishnan Vasanth.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 572 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raja, K., Vignesh, A., Lavanya, P. et al. Organosulfur Compound Identified from Striga angustifolia (D. Don) C.J. Saldanha Inhibits Lung Cancer Growth and Induces Apoptosis via p53/mTOR Signaling Pathway. Appl Biochem Biotechnol 195, 7277–7297 (2023). https://doi.org/10.1007/s12010-023-04467-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-023-04467-0

Keywords

Search

Navigation