Skip to main content

Advertisement

Springer Nature Link
Log in

Anti-cancer Effect of Hyoscyamus muticus Extract via Its Activation of Fas/FasL-ASK1-p38 Pathway

  • Research Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

An Erratum to this article was published on 24 December 2022

This article has been updated

Abstract

Hyoscyamus muticus L. is a traditional medicine used as antispasmodic and sedative. Herein, we aimed to determine the phytochemical constituents and for the first time its anti-cancer activities. The phytochemical constituents of the different extracts were evaluated by calorimetric methods. The anti-cancer activities of the extracts were tested against leukemia, breast, renal, and prostate cancers cell lines. 4, 6-Diamidino-2-phenylindole (DAPI) staining, flow cytometric analysis, knockdown of ASK1, and reactive oxygen species (ROS) production were evaluated to clarify the mechanism of action. Phytochemical screening confirmed the presence of wide range of phytoconstituents. Hyoscyamus muticus methanolic extracts (HMME) showed the highest anti-cancer activities against leukemia, breast, renal, and prostate cancers as compared to ethanol and aqueous extracts. Specifically, HMME exerted cytotoxic effect against the MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cell lines with IC50 values of 8.75 and 7.25 μg/mL, respectively. Mechanistically, DAPI staining and flow cytometric analysis revealed that HMME induces apoptosis via the death receptor, FAS, but not the mitochondrial pathway. Moreover, ASK1 and p38 were rapidly activated in response to HMME, and knockdown of ASK1 by a small interference of RNA specific to Ask1 attenuated p38 and caspase-3 activation and suppressed apoptosis, implying that HMME-induced apoptosis relies on the ASK1-p38-caspase-3 pathway. Furthermore, we confirmed that cellular ROS generation was a critical mediator in HMME-induced apoptosis because the ROS-scavenger N-acetyl cysteine significantly decreased the phosphorylation of ASK1 and HMME-induced apoptosis. Our results confirmed HMME cytotoxic effects in TNBCs via ROS-dependent activation of the Fas/FasL-ASK1-p38 axis.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data Availability

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

Change history

References

  1. Bianchini, G., J. M. Balko, I. A. Mayer, M. E. Sanders, and L. Gianni (2016) Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat. Rev. Clin. Oncol. 13: 674–690.

    Article  CAS  Google Scholar 

  2. Swain, S. (2008) Triple-negative breast cancer: metastatic risk and role of platinum agents. Proceedings of the Annual Meeting of the American Society for Clinical Oncology. May 30–June 3. Chicago, IL, USA.

    Google Scholar 

  3. den Brok, W. D., C. H. Speers, L. Gondara, E. Baxter, S. K. Tyldesley, and C. A. Lohrisch (2017) Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed. Breast Cancer Res. Treat. 161: 549–556.

    Article  Google Scholar 

  4. Hengartner, M. O. (2000) The biochemistry of apoptosis. Nature. 407: 770–776.

    Article  CAS  Google Scholar 

  5. Elmore, S. (2007) Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35: 495–516.

    Article  CAS  Google Scholar 

  6. Hongmei, Z. (2012) Extrinsic and intrinsic apoptosis signal pathway review. pp. 1–22. In: T. M. Ntuli (ed.). Apoptosis and Medicine. IntechOpen, London, UK.

    Google Scholar 

  7. Sim, K. H., M.-S. Shu, S. Kim, J.-Y. Kim, B.-H. Choi, and Y. J. Lee (2021) Cilostazol induces apoptosis and inhibits proliferation of hepatocellular carcinoma cells by activating AMPK. Biotechnol. Bioprocess Eng. 26: 776–785.

    Article  CAS  Google Scholar 

  8. Abd El-Hafeez, A. A., H. O. Khalifa, E. A. Mahdy, V. Sharma, T. Hosoi, P. Ghosh, K. Ozawa, M. M. Montano, T. Fujimura, A. R. Ibrahim, M. Abdelhamid, S. P. Pack, S. A. Shouman, and S. Kawamoto (2019) Anticancer effect of nor-wogonin (5, 7, 8-trihydroxyflavone) on human triple-negative breast cancer cells via downregulation of TAK1, NF-κB, and STAT3. Pharmacol. Rep. 71: 289–298.

    Article  CAS  Google Scholar 

  9. Abd El-Hafeez, A. A., T. Fujimura, R. Kamei, N. Hirakawa, K. Baba, K. Ono, and S. Kawamoto (2018) A methoxyflavanone derivative from the Asian medicinal herb (Perilla frutescens) induces p53-mediated G2/M cell cycle arrest and apoptosis in A549 human lung adenocarcinoma. Cytotechnology. 70: 899–912.

    Article  CAS  Google Scholar 

  10. Abd El-Hafeez, A. A., T. Fujimura, R. Kamei, N. Hirakawa, K. Baba, K. Ono, and S. Kawamoto (2018) Synergistic tumor suppression by a Perilla frutescens-derived methoxyflavanone and anti-cancer tyrosine kinase inhibitors in A549 human lung adenocarcinoma. Cytotechnology. 70: 913–919.

    Article  CAS  Google Scholar 

  11. Safarzadeh, E., S. S. Shotorbani, and B. Baradaran (2014) Herbal medicine as inducers of apoptosis in cancer treatment. Adv. Pharm. Bull. 4 Suppl 1: 421–427.

    Google Scholar 

  12. Kim, E.-J., C.-W. Kang, N.-H. Kim, Y. B. Seo, S.-W. Nam, and G.-D. Kim (2018) Induction of apoptotic cell death on human cervix cancer HeLa cells by extract from Loranthus yadoriki. Biotechnol. Bioprocess Eng. 23: 201–207.

    Article  CAS  Google Scholar 

  13. Wang, H., T. O. Khor, L. Shu, Z. Y. Su, F. Fuentes, J. H. Lee, and A. N. T. Kong (2012) Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anticancer Agents Med. Chem. 12: 1281–1305.

    Article  CAS  Google Scholar 

  14. Pham, T. N. A., B. Le, and S. H. Yang (2021) Anticancer activity of the potential Pyropia yezoensis galactan fractionated in human prostate cancer cells. Biotechnol. Bioprocess Eng. 26: 63–70.

    Article  CAS  Google Scholar 

  15. Liang, Y., D. Kong, Y. Zhang, S. Li, Y. Li, A. Ramamoorthy, and J. Ma (2020) Fisetin inhibits cell proliferation and induces apoptosis via JAK/STAT3 signaling pathways in human thyroid TPC 1 cancer cells. Biotechnol. Bioprocess Eng. 25: 197–205.

    Article  CAS  Google Scholar 

  16. Min, H.-S. and J.-H. Kim (2021) Kinetic and thermodynamic study of the ultrasonic acetone-pentane fractional precipitation of paclitaxel from the plant cell cultures of Taxus chinensis. Biotechnol. Bioprocess Eng. 26: 660–668.

    Article  CAS  Google Scholar 

  17. Koh, Y.-C., C.-T. Ho, and M.-H. Pan (2020) Recent advances in cancer chemoprevention with phytochemicals. J. Food Drug Anal. 28: 14–37.

    Article  CAS  Google Scholar 

  18. Abd El-Twab, M. H., N. A. Barakat, and A. A. Abd El-Hafeez (2010) Cytogenetical and ecological studies of some wild congeneric species in the Solanaceae distributed in upper Egypt. Chromosom Bot. 5: 65–73.

    Article  Google Scholar 

  19. Al-Snafi, A. E. (2018) Therapeutic importance of Hyoscyamus species grown in Iraq (Hyoscyamus albus, Hyoscyamus niger and Hyoscyamus reticulates)- a review. IOSR J. Pharm. 8: 18–32.

    CAS  Google Scholar 

  20. Yahia, M., M. Yahia, and A. Benhouda (2018) Antitumor activity of methanolic fractions extracted from the aerial part of Algerian Hyoscyamus albus and apoptotic cell aspect screening. Indian J. Pharm. Educ. Res. 52: 262–267.

    CAS  Google Scholar 

  21. Deepti, K., P. Umadevi, G. Vijayalakshmi, and B. Vinod polarao (2012) Antimicrobial activity and phytochemical analysis of Morinda tinctoria Roxb. leaf extracts. Asian Pac. J. Trop. Biomed. 2: S1440–S1442.

    Article  Google Scholar 

  22. Mujeeb, F., P. Bajpai, and N. Pathak (2014) Phytochemical evaluation, antimicrobial activity, and determination of bioactive components from leaves of Aegle marmelos. Biomed Res. Int. 2014: 497606.

    Article  Google Scholar 

  23. Khalifa, H. O., M. Kamimoto, T. Shimamoto, and T. Shimamoto (2015) Antimicrobial effects of blueberry, raspberry, and strawberry aqueous extracts and their effects on virulence gene expression in Vibrio cholerae. Phytother. Res. 29: 1791–1797.

    Article  CAS  Google Scholar 

  24. Kavitha Chandran, C. I. and G. Indira (2016) Quantitative estimation of total phenolic, flavonoids, tannin and chlorophyll content of leaves of Strobilanthes Kunthiana (Neelakurinji). J. Med. Plants Stud. 4: 282–286.

    Google Scholar 

  25. Abd El-Hafeez, A. A. and O. M. Rakha (2017) Paederus alfieri extract induces apoptosis in human myeloid leukemia K562 cells. Asian J. Pharm. Clin. Res. 10: 72–75.

    CAS  Google Scholar 

  26. Abd El-Hafeez, A. A., H. O. Khalifa, R. A. Elgawish, S. A. Shouman, M. H. Abd El-Twab, and S. Kawamoto (2018) Melilotus indicus extract induces apoptosis in hepatocellular carcinoma cells via a mechanism involving mitochondria-mediated pathways. Cytotechnology. 70: 831–842.

    Article  Google Scholar 

  27. Lee, S., J. H. Shim, H. Gim, H. S. Park, and B. J. Kim (2016) Ethanol extract of Oldenlandia diffusa - an effective chemotherapeutic for the treatment of colorectal cancer in humans: -anticancer effects of Oldenlandia diffusa. J. Pharmacopuncture 19: 51–58.

    Article  CAS  Google Scholar 

  28. Reed, J. C. (2000) Mechanisms of apoptosis. Am. J. Pathol. 157: 1415–1430.

    Article  CAS  Google Scholar 

  29. Nishitoh, H., A. Matsuzawa, K. Tobiume, K. Saegusa, K. Takeda, K. Inoue, S. Hori, A. Kakizuka, and H. Ichijo (2002) ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16: 1345–1355.

    Article  CAS  Google Scholar 

  30. Hattori, K., I. Naguro, C. Runchel, and H. Ichijo (2009) The roles of ASK family proteins in stress responses and diseases. Cell Commun. Signal. 7: 9.

    Article  Google Scholar 

  31. Circu, M. L. and T. Y. Aw (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 48: 749–762.

    Article  CAS  Google Scholar 

  32. Azim, H. A., M. Ghosn, K. Oualla, and L. Kassem (2020) Personalized treatment in metastatic triple-negative breast cancer: the outlook in 2020. Breast J. 26: 69–80.

    Article  Google Scholar 

  33. Paradiso, A. and C. F. Singer (2017) Therapeutic strategies in triple-negative breast cancer. Breast Care (Basel). 12: 6–7.

    Article  Google Scholar 

  34. Nurgali, K., R. T. Jagoe, and R. Abalo (2018) Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae? Front. Pharmacol. 9: 245.

    Article  Google Scholar 

  35. Abdelhamid, M. A. A. and S. P. Pack (2021) Biomimetic and bioinspired silicifications: recent advances for biomaterial design and applications. Acta Biomater. 120: 38–56.

    Article  CAS  Google Scholar 

  36. Abdelhamid, M. A. A., K. B. Yeo, M. R. Ki, and S. P. Pack (2019) Self-encapsulation and controlled release of recombinant proteins using novel silica-forming peptides as fusion linkers. Int. J. Biol. Macromol. 125: 1175–1183.

    Article  CAS  Google Scholar 

  37. Nguyen, T. K. M., M. R. Ki, R. G. Son, K. H. Kim, J. Hong, and S. P. Pack (2021) Synthesis of sub-50 nm bio-inspired silica particles using a C-terminal-modified ferritin template with a silica-forming peptide. J. Ind. Eng. Chem. 101: 262–269.

    Article  CAS  Google Scholar 

  38. Ki, M.-R., T. K. M. Nguyen, H. S. Jun, and S. P. Pack (2018) Biosilica-enveloped ferritin cage for more efficient drug deliveries. Process Biochem. 68: 182–189.

    Article  CAS  Google Scholar 

  39. Ki, M.-R., J. K. Kim, S. H. Kim, T. K. M. Nguyen, K. H. Kim, and S. P. Pack (2020) Compartment-restricted and rate-controlled dual drug delivery system using a biosilica-enveloped ferritin cage. J. Ind. Eng. Chem. 81: 367–374.

    Article  CAS  Google Scholar 

  40. Alghazeer, R., H. El-Saltani, N. Saleh, A. Al-Najjar, and F. Hebail (2012) Antioxidant and antimicrobial properties of five medicinal Libyan plants extracts. Nat. Sci. (Irvine) 4: 324–335.

    CAS  Google Scholar 

  41. Jassbi, A. R., R. Miri, M. Masroorbabanari, M. Asadollahi, M. Attarroshan, and I. T. Baldwin (2014) HPLC-DAD-ESIMS analyses of Hyoscyamus niger and H. reticulatus for their antioxidant constituents. Austin Chromatogr. 1: 1022.

    Google Scholar 

  42. Hossain, M. A., A. M. Weli, and S. H. I. Ahmed (2019) Comparison of total phenols, flavonoids and antioxidant activity of various crude extracts of Hyoscyamus gallagheri traditionally used for the treatment of epilepsy. Clin. Phytoscience. 5: 20.

    Article  Google Scholar 

  43. Lee, M. M.-L., B. D. Chan, W.-Y. Wong, Z. Qu, M.-S. Chan, T.-W. Leung, Y. Lin, D. K.-W. Mok, S. Chen, and W. C.-S. Tai (2020) Anti-cancer activity of Centipeda minima extract in triple negative breast cancer via inhibition of AKT, NF-κB, and STAT3 signaling pathways. Front. Oncol. 10: 491.

    Article  Google Scholar 

  44. Sofi, M. S., M. K. Sateesh, M. Bashir, G. Harish, T. R. Lakshmeesha, S. Vedashree, and A. B. Vedamurthy (2013) Cytotoxic and proapoptotic effects of Abrus precatorius L. on human metastatic breast cancer cell line, MDA-MB-231. Cytotechnology. 65: 407–417.

    Article  Google Scholar 

  45. Song, H., S. Zhang, J. Mou, G. Gong, Y. Huang, R. Ma, H. Wang, and Q. Tan (2019) Cytotoxic activities against MCF-7 and MDAMB-231, antioxidant and α-glucosidase inhibitory activities of Trachelospermum jasminoides extracts in vitro. Biotechnol. Biotechnol. Equip. 33: 1671–1679.

    Article  CAS  Google Scholar 

  46. Firoozinia, M., S. Z. Moghadamtousi, A. Sadeghilar, H. Karimian, and M. I. B. Noordin (2015) Golden natural plant compounds activate apoptosis via both mitochondrial and death receptor pathways: a review. Electron. J. Biol. 11: 126–137.

    Google Scholar 

  47. Walczak, H. (2013) Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harb. Perspect. Biol. 5: a008698.

    Article  Google Scholar 

  48. Chang, H. Y., H. Nishitoh, X. Yang, H. Ichijo, and D. Baltimore (1998) Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science. 281: 1860–1863.

    Article  CAS  Google Scholar 

  49. Ichijo, H., E. Nishida, K. Irie, P. ten Dijke, M. Saitoh, T. Moriguchi, M. Takagi, K. Matsumoto, K. Miyazono, and Y. Gotoh (1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 275: 90–94.

    Article  CAS  Google Scholar 

  50. Nakagawa, H., Y. Hirata, K. Takeda, Y. Hayakawa, T. Sato, H. Kinoshita, K. Sakamoto, W. Nakata, Y. Hikiba, M. Omata, H. Yoshida, K. Koike, H. Ichijo, and S. Maeda (2011) Apoptosis signal-regulating kinase 1 inhibits hepatocarcinogenesis by controlling the tumor-suppressing function of stress-activated mitogen-activated protein kinase. Hepatology. 54: 185–195.

    Article  CAS  Google Scholar 

  51. White, D. E. and S. A. Burchill (2010) Fenretinide-dependent upregulation of death receptors through ASK1 and p38α enhances death receptor ligand-induced cell death in Ewing’s sarcoma family of tumours. Br. J. Cancer. 103: 1380–1390.

    Article  CAS  Google Scholar 

  52. Kavurma, M. M. and L. M. Khachigian (2003) Signaling and transcriptional control of Fas ligand gene expression. Cell Death Differ. 10: 36–44.

    Article  CAS  Google Scholar 

  53. Halasi, M., M. Wang, T. S. Chavan, V. Gaponenko, N. Hay, and A. L. Gartel (2013) ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors. Biochem. J. 454: 201–208.

    Article  CAS  Google Scholar 

  54. Sun, X., W. Wang, J. Chen, X. Cai, J. Yang, Y. Yang, H. Yan, X. Cheng, J. Ye, W. Lu, C. Hu, H. Sun, J. Pu, and P. Cao (2017) The natural diterpenoid isoforretin A inhibits thioredoxin-1 and triggers potent ROS-mediated antitumor effects. Cancer Res. 77: 926–936.

    Article  CAS  Google Scholar 

  55. Kamata, H., S. Honda, S. Maeda, L. Chang, H. Hirata, and M. Karin (2005) Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 120: 649–661.

    Article  CAS  Google Scholar 

  56. Noguchi, T., K. Takeda, A. Matsuzawa, K. Saegusa, H. Nakano, J. Gohda, J. Inoue, and H. Ichijo (2005) Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death. J. Biol. Chem. 280: 37033–37040.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Amer Ali Abd El-Hafeez was supported by an NIH-funded Cancer Therapeutics Training Program (CT2, T32 CA121938), Pradipta Ghosh by the NIH (CA238042, CA100768, and CA160911), Ahmed R. N. Ibrahim by the Institute of Research and Consulting Studies at King Khalid University grant (15-102-S-2020). This work also was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2021R1A5A8032895, NRF-2021R1A2C2011564).

Author information

Author notes

  1. Amer Ali Abd El-Hafeez, Hala Mohamed M. Marzouk, Mohamed A. A. Abdelhamid, and Hazim O. Khalifa contributed equally to this work.

Authors and Affiliations

  1. Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt

    Amer Ali Abd El-Hafeez

  2. Department of Biotechnology and Bioinformatics, Korea University, Sejong, 30019, Korea

    Mohamed A. A. Abdelhamid & Seung Pil Pack

  3. Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA

    Amer Ali Abd El-Hafeez, Hala Mohamed M. Marzouk & Pradipta Ghosh

  4. Department of Biochemistry, Faculty of Medicine, Minia University, El-Minia, 61519, Egypt

    Hala Mohamed M. Marzouk

  5. Department of Botany and Microbiology, Faculty of Science, Minia University, Minia, 61519, Egypt

    Mohamed A. A. Abdelhamid

  6. Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, 33516, Egypt

    Hazim O. Khalifa

  7. Department of Chemistry, College of Science, Jouf University, Sakaka, 2014, Saudi Arabia

    Tamer H. A. Hasanin

  8. Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, 62511, Egypt

    Ahmed G. K. Habib

  9. Medical Biochemistry and Molecular Biology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt

    Fatma Mahmoud Abdelwahed

  10. Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt

    Fatma M. Barakat

  11. Deakin University, School of Medicine, Waurn Ponds, Victoria, 3216, Australia

    Eslam M. Bastawy

  12. Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8530, Japan

    Eman M. B. Abdelghani, Takashi Fujimura & Seiji Kawamoto

  13. Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, 756-0884, Japan

    Toru Hosoi

  14. Pharmacotherapy Department, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan

    Koichiro Ozawa

  15. Faculty of Biotechnology, Modern Sciences and Arts University (MSA), Giza, 11511, Egypt

    Ahmed M. Aref

  16. Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia

    Ahmed R. N. Ibrahim

  17. Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, 61511, Egypt

    Ahmed R. N. Ibrahim

  18. Faculty of Pharmacy, Deraya University, New Minia, 61111, Egypt

    Aalaa S. O. Abdelmoniem

  19. Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, 11591, Egypt

    Hagar Elghazawy

Authors
  1. Amer Ali Abd El-Hafeez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hala Mohamed M. Marzouk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamed A. A. Abdelhamid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hazim O. Khalifa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tamer H. A. Hasanin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ahmed G. K. Habib
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fatma Mahmoud Abdelwahed
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fatma M. Barakat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eslam M. Bastawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eman M. B. Abdelghani
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Toru Hosoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Koichiro Ozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ahmed M. Aref
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takashi Fujimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ahmed R. N. Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Aalaa S. O. Abdelmoniem
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hagar Elghazawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Pradipta Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Seiji Kawamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Seung Pil Pack
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Amer Ali Abd El-Hafeez or Seung Pil Pack.

Ethics declarations

The authors declare no conflict of interest.

Neither ethical approval nor informed consent was required for this study.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abd El-Hafeez, A.A., Marzouk, H.M.M., Abdelhamid, M.A.A. et al. Anti-cancer Effect of Hyoscyamus muticus Extract via Its Activation of Fas/FasL-ASK1-p38 Pathway. Biotechnol Bioproc E 27, 833–845 (2022). https://doi.org/10.1007/s12257-022-0085-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-022-0085-x

Keywords

Search

Navigation