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Thymoquinone Modulates Gene Expression Associated with Apoptosis in Colorectal Cancer: A Preclinical Systematic

Muhammad Evy Prastiyanto1, Kuncara Nata Waskita2, Rina Nurmaulawati2

  • 1Department of Medical Laboratory Technology, Faculty of Health and Nursing Science, Universitas Muhammadiyah Semarang, Semarang, 50273, Indonesia.

Abstract

Insights

Thymoquinone (TQ) shows promise in fighting colorectal cancer (CRC) by promoting cancer cell death. This review confirms TQ increases pro-apoptotic markers (BAX, CASP3) and decreases anti-apoptotic markers (BCL2) in CRC models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Colorectal cancer (CRC) remains a major global health concern.
  • Thymoquinone (TQ), derived from Nigella sativa, exhibits anticancer properties by inducing apoptosis.
  • Understanding TQ's effects on apoptosis-regulating markers is crucial for CRC research.

Purpose of the Study:

  • To systematically review and meta-analyze the impact of TQ on pro-apoptotic (BAX, CASP3) and anti-apoptotic (BCL2) markers in colorectal cancer.
  • To quantify the effects of TQ on these key apoptosis markers in various CRC models.

Main Methods:

  • Systematic literature search across Scopus, BASE, PubMed, and Web of Science (2004-2025).
  • Inclusion of in vitro and in vivo studies reporting BAX, BCL2, and CASP3 expression data.
  • Random-effects model meta-analysis to calculate effect sizes (g) and assess heterogeneity and publication bias.

Main Results:

  • Meta-analysis of 10 studies showed TQ significantly upregulated BAX (mRNA: g=3.901, protein: g=4.232) and CASP3 (mRNA: g=5.669, protein: g=6.336).
  • TQ significantly downregulated BCL2 (mRNA: g=-3.680, protein: g=-3.328) across various CRC cell lines.
  • Low to moderate heterogeneity and low/non-significant publication bias were observed.

Conclusions:

  • TQ demonstrates pro-apoptotic effects in colorectal cancer models by upregulating BAX and CASP3 and downregulating BCL2.
  • These findings suggest TQ's potential therapeutic relevance in CRC treatment.
  • Further in vivo and early-phase clinical studies are warranted to confirm translational significance and treatment implications.

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