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Geraniol Inhibits Endometrial Carcinoma via Downregulating Oncogenes and Upregulating Tumour Suppressor Genes
Sakkaravarthy Shanmugapriya1, Perumal Subramanian1, Sivamani Kanimozhi1
1Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Tamil Nadu 608 002 India.
Abstract:
Endometrial carcinoma is the fourth most abundant cancer worldwide in women. Female Wistar rats were segregated into five groups: group I-control, group II-MNNG (N-methyl-N'-nitro-N-nitrosoguanidine-150 mg/kg) administered through intravaginal detention of cotton absorbent, group III-geraniol (GOH) only, group IV-GOH-pretreated (7 days before the start of MNNG administration); and group V-Co-administration of geraniol with MNNG. In this study, reverse transcriptase- PCR of K-ras, MAPK, PI3K, Wnt/β-catenin genes, TGF-β and expressions of PCNA, PTEN, progesterone receptor and E-cadherin by Western blotting were performed from endometrial cancer tissue and control tissues. The mRNA expressions of K-ras, MAPK, PI3K, Wnt/β-catenin and TGF-β were amplified in MNNG induced group. Oral administration of GOH (both pre and co-administration) reversed the mRNA expression towards normal. The reversibility is more predominant in pretreatment groups (p < 0.05). The expression of PCNA was upregulated and downregulation of PTEN, progesterone receptor and E-cadherin was noticed in MNNG induced rats. Pre and co-administration of GOH significantly reversed the expression pattern of proteins. GOH treatment is more effective in pretreatment groups (p < 0.05). These results provide powerful evidences that GOH could influence modulation of MAPK pathways and Wnt signalling pathways in the prevention of endometrial carcinoma in rats.
Insights
Geraniol (GOH) shows promise in preventing endometrial carcinoma by reversing gene expression changes induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Pretreatment with geraniol was more effective in restoring normal gene and protein expression in rats.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Endometrial carcinoma is a significant global health concern for women.
- N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a chemical carcinogen used to induce endometrial cancer in research models.
- Geraniol (GOH) is a naturally occurring monoterpenoid with potential therapeutic properties.
Purpose of the Study:
- To investigate the chemopreventive effects of geraniol (GOH) on MNNG-induced endometrial carcinoma in Wistar rats.
- To analyze the impact of GOH on key molecular pathways involved in endometrial cancer development, including MAPK and Wnt signaling.
Main Methods:
- Female Wistar rats were divided into five groups: control, MNNG-induced cancer, GOH only, GOH-pretreated, and GOH co-administered with MNNG.
- Gene expression (K-ras, MAPK, PI3K, Wnt/β-catenin, TGF-β) was analyzed using reverse transcriptase-PCR.
- Protein expression (PCNA, PTEN, progesterone receptor, E-cadherin) was assessed by Western blotting.
Main Results:
- MNNG administration led to increased mRNA expression of K-ras, MAPK, PI3K, Wnt/β-catenin, and TGF-β.
- GOH administration (both pre- and co-administration) reversed these aberrant mRNA expressions towards normal levels, with greater efficacy in the pretreatment group.
- MNNG induced upregulation of PCNA and downregulation of PTEN, progesterone receptor, and E-cadherin.
- GOH treatment significantly reversed these protein expression patterns, particularly in the pretreatment group.
Conclusions:
- Geraniol (GOH) demonstrates significant chemopreventive potential against endometrial carcinoma.
- GOH effectively modulates MAPK and Wnt signaling pathways, suggesting a role in cancer prevention.
- Pretreatment with GOH appears to be a more effective strategy than co-administration for preventing MNNG-induced endometrial cancer in rats.
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