Polifenolce zengin pimenta dioica ekstraktı over kanseri hücrelerinde mitokondriyal apoptozu indükler
Abstract
Amaç: Over kanseri, kadınlarda en yüksek ölüm oranına sahip jinekolojik malignitedir ve diğer tüm kadın üreme sistemi kanserlerinden daha fazla ölüme yol açmaktadır. Standart kemoterapi, zamanla gelişen kemorezistans ve toksik yan etkiler nedeniyle sıklıkla başarısız olur; bu da beş yıllık sağkalım oranlarının %40’ın altında kalmasına neden olur. Son yıllarda, fitokimyasalların çok yönlü etki mekanizmaları ve görece düşük toksisite profilleri nedeniyle potansiyel antikanser ajanlar olarak değerlendirilmelerine yönelik akademik ilgi artmaktadır. Pimenta dioica (yenibahar) meyveleri, eugenol ve gallik asit gibi biyoaktif bileşenler içeren, antioksidan açısından zengin bitkilerdir ve antiproliferatif özellikleri bildirilmiştir. Ancak, over kanseri üzerindeki etkileri büyük ölçüde araştırılmamıştır.
Gereç ve Yöntem: Pimenta dioica ekstresi, insan over adenokarsinom hücre hattı OVCAR-3 üzerinde değerlendirildi. Sitotoksisite, 12.5-200 µg/mL doz aralığında ve 48-72 saatlik inkübasyon sürelerinde WST-1 canlılık testi ile değerlendirilerek IC₅₀ değerleri belirlendi. Apoptoz indüksiyonu, Annexin V-FITC/PI boyaması kullanılarak akış sitometrisi ile analiz edildi. Apoptozla ilişkili genlerin (BAX, BCL-2, CASP3, CASP9 ve TP53) ekspresyon düzeyleri qRT-PCR yöntemiyle ölçüldü.
Bulgular: Pimenta dioica ekstresi, OVCAR-3 hücre canlılığını doza ve zamana bağımlı şekilde anlamlı olarak inhibe etti (p<0.05). 72 saatlik IC₅₀ değeri 92 µg/mL olarak belirlendi ve bu, orta düzeyde sitotoksik aktiviteye işaret etti. Gen ekspresyon analizleri, pro-apoptotik aracılar (BAX, CASP3, CASP9, TP53) düzeylerinde artış ve anti-apoptotik BCL-2 düzeyinde azalma gösterdi (p<0.05).
Sonuç: Pimenta dioica ekstresi, over kanseri hücreleri üzerinde sitotoksik ve pro-apoptotik etkiler göstermektedir. Bu bulgular, yenibahar kaynaklı fitokimyasalların OVCAR-3 hücrelerinde apoptoz yolaklarını aktive ettiğini ve doğal antikanser ajanlar olarak potansiyel taşıdıklarını göstermektedir. P. dioica’nın adjuvan tedavilerde veya kemopreventif stratejilerde kullanılabilirliğini ilerletmek için in vivo çalışmalar ve fitokimyasalların izolasyonu gereklidir
References
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- Kim JH, Lee YJ, Park JY, et al. A randomized, multicenter, open-label phase III trial of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in platinum-resistant recurrent ovarian cancer: a rationale and study design of the KOV-HIPEC-02 trial. Int J Gynecol Cancer. 2025;35(4):101630.
- Yang L, Xie HJ, Li YY, Wang X, Liu XX, Mai J. Molecular mechanisms of platinum-based chemotherapy resistance in ovarian cancer (review). Oncol Rep. 2022;47(4):82. doi:10.3892/or.2022.8293.
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- Wang C, Gao P, Xu J, Liu S, Tian W, Liu J, Zhou L. Natural phytochemicals prevent side effects in BRCA-mutated ovarian cancer and PARP inhibitor treatment. Front Pharmacol. 2022;13:1078303. doi:10.3389/fphar.2022.1078303.
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- Zhang L, Lokeshwar BL. Medicinal properties of the Jamaican pepper plant Pimenta dioica and allspice. Curr Drug Targets. 2012;13(14):1900-1906. doi:10.2174/138945012804545641.
- Murali V, Devi V, Parvathy P, Murugan M. Phytochemical screening, FTIR spectral analysis, antioxidant and antibacterial activity of leaf extract of Pimenta dioica Linn. Mater Today Proc. 2020;45:–. doi:10.1016/j.matpr.2020.10.038.
- Premachandran M, Murthy P. Ethnobotanical, phytochemical, pharmacological properties and applications of Pimenta dioica L. J Essent Oil Res. 2022;34:216-232. doi:10.1080/10412905.2022.2032423.
- Moghtaderi H, Sepehri H, Delphi L, Attari F. Gallic acid and curcumin induce cytotoxicity and apoptosis in human breast cancer cell MDA-MB-231. Bioimpacts. 2018;8(3):185-194. doi:10.15171/bi.2018.21.
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- Williams R, Patel U, Doyle BJ, Locklear TD, Perez AL, Mahady GB. Antiestrogenic and anti-HER2 activities of allspice (Pimenta dioica L., Myrtaceae) extracts in MCF-7 and SK-BR3 breast cancer cells. Planta Med. 2014;80:PP28. doi:10.1055/s-0034-1382723.
- Padhy I, Paul P, Sharma T, Banerjee S, Mondal A. Molecular mechanisms of action of eugenol in cancer: recent trends and advancement. Life (Basel). 2022;12(11):1795. doi:10.3390/life12111795.
- Sasidharan A, Surendran A, Rajagopal R, Alfarhan A, Job JT, Narayanankutty A. Allspice (Pimenta dioica) essential oil mediates sphingosine kinase inhibition and subsequent induction of apoptosis in gastric cancer cells. J Essent Oil Bear Plants. 2024;27(2):537-546. doi:10.1080/0972060X.2024.2333778.
- Shamaladevi N, Lyn DA, Shaaban KA, Zhang L, Villate S, Rohr J, Lokeshwar BL. Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer. Carcinogenesis. 2013;34(8):1822-1832. doi:10.1093/carcin/bgt123.s
- Cunha MR, Tavares MT, Fernandes TB, Parise-Filho R. Peppers: a “hot” natural source for antitumor compounds. Molecules. 2021;26(6):1521. doi:10.3390/molecules26061521.
- Fathy M, Fawzy MA, Hintzsche H, Nikaido T, Dandekar T, Othman EM. Eugenol exerts apoptotic effect and modulates the sensitivity of HeLa cells to cisplatin and radiation. Molecules. 2019;24(21):3979. doi:10.3390/molecules24213979.
Abstract
Aim: Ovarian cancer is a highly lethal gynecologic malignancy, accounting for more deaths than any other female reproductive cancer. Standard chemotherapy often fails over time due to chemoresistance and toxic side effects, resulting in poor five-year survival rates under 40%. There exists an increasing scholarly interest in phytochemicals as potential anticancer agents, attributable to their multifaceted mechanisms of action and comparatively reduced toxicity profiles. Pimenta dioica (allspice) berries are rich in antioxidants and contain bioactive compounds such as eugenol and gallic acid with reported antiproliferative properties. However, their effects in ovarian cancer remain underexplored.
Materials and Methods: P. dioica extract was evaluated on human ovarian adenocarcinoma OVCAR-3 cells. Cytotoxicity was assessed by WST-1 viability assays across a 12.5-200 µg/mL dose range (48-72 h exposure) to determine IC₅₀ values. Apoptosis induction was analyzed by Annexin V-FITC /PI via flow cytometry. Expression of apoptosis related genes (BAX, BCL-2, CASP3, CASP9 and TP53) was quantified by qRT-PCR.
Results: P. dioica extract inhibited OVCAR-3 cell viability in dose and time dependent manner (p<0.05). The 72 h IC₅₀ was 92 µg/mL, indicating moderate cytotoxic activity. Gene expression analysis revealed upregulation of pro-apoptotic mediators (BAX, CASP3, CASP9, TP53) and concomitant downregulation of anti-apoptotic BCL-2 (p<0.05).
Conclusion: P. dioica extract exerts cytotoxic and pro-apoptotic influences on ovarian cancer cells. These findings suggest that allspice-derived phytochemicals trigger apoptosis pathways in OVCAR-3 cells, supporting their potential as natural anti-cancer agents. Subsequent in vivo investigations and the isolation of phytochemicals are imperative to advance the development of adjuvant therapies utilizing P. dioica or chemopreventive strategies for ovarian cancer
References
- Hong M-K, Ding D-C. Early diagnosis of ovarian cancer: a comprehensive review of the advances, challenges, and future directions. Diagnostics. 2025;15(4):406. doi:10.3390/diagnostics15040406
- Kim JH, Lee YJ, Park JY, et al. A randomized, multicenter, open-label phase III trial of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in platinum-resistant recurrent ovarian cancer: a rationale and study design of the KOV-HIPEC-02 trial. Int J Gynecol Cancer. 2025;35(4):101630.
- Yang L, Xie HJ, Li YY, Wang X, Liu XX, Mai J. Molecular mechanisms of platinum-based chemotherapy resistance in ovarian cancer (review). Oncol Rep. 2022;47(4):82. doi:10.3892/or.2022.8293.
- Petrović N, Matić IZ, Stanojković T. Natural compounds and strategies for fighting against drug resistance in cancer: a special focus on phenolic compounds and microRNAs. Am J Physiol Cell Physiol. 2025;329(1):C183-C199. doi:10.1152/ajpcell.00456.2024.
- Wang C, Gao P, Xu J, Liu S, Tian W, Liu J, Zhou L. Natural phytochemicals prevent side effects in BRCA-mutated ovarian cancer and PARP inhibitor treatment. Front Pharmacol. 2022;13:1078303. doi:10.3389/fphar.2022.1078303.
- Moazzami B, Chaichian S, Nikfar B, Arbabi Bidgoli S. Modulation of microRNAs expression and cellular signaling pathways through curcumin as a potential therapeutical approach against ovarian cancer: a review. Pathol Res Pract. 2023;247:154527. doi:10.1016/j.prp.2023.154527.
- Karaosmanoğlu Ö, Kamalak Z, Özdemir İ, Öztürk Ş, Tuncer MC. Apoptotic effect of thymoquinone on OVCAR3 cells via the P53 and CASP3 activation. Acta Cir Bras. 2024;39:e399224. doi:10.1590/acb399224.
- Shamaladevi N, Lyn DA, Villate S, Lokeshwar BL. An aqueous extract of allspice (Pimenta dioica) suppresses androgen receptor expression and prostate cancer growth. Cancer Res. 2011;71(8 Suppl):5572. doi:10.1158/1538-7445.AM2011-5572.
- Nagalakshmi K, Angeline R, Prasath G. Phytochemical characterisation, antioxidant and antimicrobial efficacy of allspice (Pimenta dioica). Res J Pharm Technol. 2023;16(9):-. doi:10.52711/0974-360x.2023.00952.
- Zhang L, Lokeshwar BL. Medicinal properties of the Jamaican pepper plant Pimenta dioica and allspice. Curr Drug Targets. 2012;13(14):1900-1906. doi:10.2174/138945012804545641.
- Murali V, Devi V, Parvathy P, Murugan M. Phytochemical screening, FTIR spectral analysis, antioxidant and antibacterial activity of leaf extract of Pimenta dioica Linn. Mater Today Proc. 2020;45:–. doi:10.1016/j.matpr.2020.10.038.
- Premachandran M, Murthy P. Ethnobotanical, phytochemical, pharmacological properties and applications of Pimenta dioica L. J Essent Oil Res. 2022;34:216-232. doi:10.1080/10412905.2022.2032423.
- Moghtaderi H, Sepehri H, Delphi L, Attari F. Gallic acid and curcumin induce cytotoxicity and apoptosis in human breast cancer cell MDA-MB-231. Bioimpacts. 2018;8(3):185-194. doi:10.15171/bi.2018.21.
- Zhang L, Shamaladevi N, Jayaprakasha GK, Patil BS, Lokeshwar BL. Polyphenol-rich extract of Pimenta dioica berries (allspice) kills breast cancer cells by autophagy and delays growth of triple-negative breast cancer in athymic mice. Oncotarget. 2015;6(18):16379-95. doi:10.18632/oncotarget.3834.
- Williams R, Patel U, Doyle BJ, Locklear TD, Perez AL, Mahady GB. Antiestrogenic and anti-HER2 activities of allspice (Pimenta dioica L., Myrtaceae) extracts in MCF-7 and SK-BR3 breast cancer cells. Planta Med. 2014;80:PP28. doi:10.1055/s-0034-1382723.
- Padhy I, Paul P, Sharma T, Banerjee S, Mondal A. Molecular mechanisms of action of eugenol in cancer: recent trends and advancement. Life (Basel). 2022;12(11):1795. doi:10.3390/life12111795.
- Sasidharan A, Surendran A, Rajagopal R, Alfarhan A, Job JT, Narayanankutty A. Allspice (Pimenta dioica) essential oil mediates sphingosine kinase inhibition and subsequent induction of apoptosis in gastric cancer cells. J Essent Oil Bear Plants. 2024;27(2):537-546. doi:10.1080/0972060X.2024.2333778.
- Shamaladevi N, Lyn DA, Shaaban KA, Zhang L, Villate S, Rohr J, Lokeshwar BL. Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer. Carcinogenesis. 2013;34(8):1822-1832. doi:10.1093/carcin/bgt123.s
- Cunha MR, Tavares MT, Fernandes TB, Parise-Filho R. Peppers: a “hot” natural source for antitumor compounds. Molecules. 2021;26(6):1521. doi:10.3390/molecules26061521.
- Fathy M, Fawzy MA, Hintzsche H, Nikaido T, Dandekar T, Othman EM. Eugenol exerts apoptotic effect and modulates the sensitivity of HeLa cells to cisplatin and radiation. Molecules. 2019;24(21):3979. doi:10.3390/molecules24213979.
Details
| Primary Language | English |
|---|---|
| Subjects | Medical Genetics (Excl. Cancer Genetics) |
| Journal Section | Research Article |
| Authors | |
| Submission Date | November 4, 2025 |
| Acceptance Date | November 16, 2025 |
| Publication Date | March 9, 2026 |
| DOI | https://doi.org/10.19161/etd.1817431 |
| IZ | https://izlik.org/JA24FS76RN |
| Published in Issue | Year 2026 Volume: 65 Issue: 1 |
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