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Hispidulin: a promising anticancer agent and mechanistic breakthrough for targeted cancer therapy

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Abstract

Cancer is a complex disease characterized by dysregulated cell growth and division, posing significant challenges for effective treatment. Hispidulin, a flavonoid compound, has shown promising biological effects, particularly in the field of anticancer research. The main objective of this study is to investigate the anticancer properties of hispidulin and gain insight into its mechanistic targets in cancer cells. A comprehensive literature review was conducted to collect data on the anticancer effects of hispidulin. In vitro and in vivo studies were analyzed to identify the molecular targets and underlying mechanisms through which hispidulin exerts its anticancer activities. Hispidulin has shown significant effects on various aspects of cancer, including cell growth, proliferation, cell cycle regulation, angiogenesis, metastasis, and apoptosis. It has been observed to target both extrinsic and intrinsic apoptotic pathways, regulate cell cycle arrest, and modulate cancer progression pathways. The existing literature highlights the potential of hispidulin as a potent anticancer agent. Hispidulin exhibits promising potential as a therapeutic agent for cancer treatment. Its ability to induce apoptosis and modulate key molecular targets involved in cancer progression makes it a valuable candidate for further investigation. Additional pharmacological studies are needed to fully understand the specific targets and signaling pathways influenced by hispidulin in different types of cancer. Further research will contribute to the successful translation of hispidulin into clinical settings, allowing its utilization in conventional and advanced cancer therapies with improved therapeutic outcomes and reduced side effects.

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Abbreviations

AKT:

serine/threonine kinase

AMPK:

AMP-activated protein kinase

BAK:

BCL2 antagonist killer 1

BAX:

BCL2-associated X protein

Bcl-2:

B-cell lymphoma protein 2

Bcl-XL:

BCL2-related protein, long isoform

CARD:

caspase recruitment domain

Caspase-10:

cysteinyl aspartic acid-protease-10

Caspase-3:

cysteinyl aspartic acid-protease-3

Caspase-6:

cysteinyl aspartic acid-protease-6

Caspase-7:

cysteinyl aspartic acid-protease-7

caspase-8:

cysteinyl aspartic acid-protease 8

COX-2 :

cyclooxygenase-2

DED:

death effector domain

ERK:

extracellular signal-regulated kinase

FasL:

Fas ligand

FasR:

Fas ligand-receptor

GBM:

glioblastoma multiforme

GLOBOCAN :

global cancer incidence, mortality, and prevalence

GSH/GSSG:

reduced glutathione/oxidized glutathione

HIF-1:

hypoxia-inducible factor-1

HIS:

hispidulin

HT-29 :

human colorectal adenocarcinoma cell line

JAK:

Janus kinase

MMP-2:

matrix metalloproteinase-2

mTOR:

mammalian target of rapamycin

OVX:

ovariectomy

PARP:

poly (ADP-ribose) polymerase

PI3K/:

phosphoinositide 3-kinase

PTEN:

phosphatase and tensin homolog

RCC:

renal cell carcinoma

ROS:

reactive oxygen species

STAT3:

signal transducer and activator of transcription 3

TMZ:

temozolomide

TNFR1:

type 1 TNF receptor

TRAIL:

TNF-related apoptosis-inducing ligand

TUNEL:

terminal deoxynucleotidyl transferase dUTP nick end labeling

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Funding

The authors received the UMT for TAPERG/2021/UMT/807 grant provided to G. C.

Author information

Authors and Affiliations

  1. Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Kuala Terengganu, Malaysia

    Gul-e-Saba Chaudhry &  Zeenia

  2. Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador

    Javad Sharifi-Rad

  3. Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania

    Daniela Calina

Authors
  1. Gul-e-Saba Chaudhry
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  2. Zeenia
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  3. Javad Sharifi-Rad
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  4. Daniela Calina
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Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas. That is, revising or critically reviewing the article; giving final approval of the version to be published; agreeing on the journal to which the article has been submitted; and, confirming to be accountable for all aspects of the work. The authors confirm that no paper mill and artificial intelligence was used.

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Correspondence to Gul-e-Saba Chaudhry, Javad Sharifi-Rad or Daniela Calina.

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Chaudhry, GeS., Zeenia, Sharifi-Rad, J. et al. Hispidulin: a promising anticancer agent and mechanistic breakthrough for targeted cancer therapy. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1919–1934 (2024). https://doi.org/10.1007/s00210-023-02645-9

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