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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.
Objective:
Colorectal cancer (CRC) continues to be a significant global health issue. Thymoquinone (TQ), a bioactive component of Nigella sativa, has shown anticancer capabilities by inducing apoptosis. This systematic review and meta-analysis aim to assess the impact of TQ on the levels of pro-apoptotic (BAX, CASP3) and anti-apoptotic (BCL2) markers in colorectal cancer cells.
Methods:
An extensive literature search was performed in Scopus, BASE, PubMed, and Web of Science for articles published from 2004 to 2025, adhering to PRISMA guidelines. Eligible in vitro and in vivo studies provided numerical data on gene or protein expression levels for BAX, BCL2, and CASP3, along with standard deviations. Effect sizes (g) were computed using a random-effects model, and heterogeneity and publication bias were evaluated.
Result:
A total of ten qualifying studies were incorporated. The meta-analysis indicated that TQ significantly (p < 0.001) increased BAX mRNA (g = 3.901) and protein levels (g = 4.232), decreased BCL2 mRNA (g = -3.680) and protein levels (g = -3.328), and markedly upregulated CASP3 mRNA (g = 5.669) and protein levels (g = 6.336). Subgroup analyses revealed consistent effects across CRC cell lines (HT29, SW480, SW620, HCT-15, and HCT116). Heterogeneity varied from low to moderate, and publication bias was low or not significant.
Conclusion:
The findings demonstrate that TQ exerts pro-apoptotic effects in colorectal cancer (CRC) models through the upregulation of BAX and CASP3 and the downregulation of BCL2. This suggests its potential therapeutic relevance rather than definitive biomarker utility. Nevertheless, further in vivo studies and early-phase clinical investigations are required to clarify its translational significance and to explore its possible implications for treatment responsiveness.
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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