The Therapeutic Effect of Turmeric Extract on Apoptotic Markers in Rats with Breast Cancer Treated with Zovegalisib

Authors

  • Zainab Mohammed Jasim Department of Human Anatomy, College of Medicine, University of Babylon, Iraq

Keywords:

Turmeric Extract, Zovegalisib, Breast Cancer, Apoptosis

Abstract

Background: Breast cancer (BC) is still one of the significant causes of both morbidity/worldwide mortality among women. In recent years, natural products have become a hot topic as adjuvant therapy, to improve efficacy and reduce toxicities in cancer treatment.

Objectives: The aim of the present study is to investigate the therapeutic influence of turmeric (Curcuma longa) extracts on apoptotic markers in zovegalisib-treated breast cancer-induced rats paying special attention to its ability enhance the apoptosis and histopathological improvements.

Methods: Twenty-eight female albino rats were distributed randomly into 4 groups (n = 10 in each group); Group 1 (DMBA control), Group 2 (DMBA + zovegalisib), Group 3 (DMBA + zovegalisib + turmeric125mg/kg) and lastly Group 4(DMBA + zovegalisib+ turmeric150 mg /kg). Breast Cancer was initiated with 7,12-dimethylbenz[a] anthracene (DMBA). Treatments were continued for 12 weeks, and breast tissues were analyzed for apoptotic markers (Caspase-7, Cytochrome c and Bcl-2) expression levels accompanied by histopathological alterations.

Results: DMBA control (G1) showed significantly decreased Caspase-7 and Cytochrome c while Bcl-2 higher expression was noticed implicated in apoptosis inhibition. Zovegalisib treatment alone (G2) moderately increased the apoptotic effect, whereas its combination with turmeric extracts led to a significant up regulation of Caspase-7 and Cytochrome c and downregulation of Bcl-2 (G3 and G4). These observations were confirmed by histopathological analysis, where they were observed a severe recovery of the tissue architecture; group 4 presented more obvious apoptotic features and fewer malignant cells. Conclusion: Turmeric extract enhances zovegalisib therapeutic activity in breast cancer through apoptotic modulators regulation and tumor cell apoptosis induction. The synergistic effect was dose-dependent: high dose (150 mg/kg) showed the most beneficial protective and restorative.

References

Ameer, S. F., Mohamed, M. Y., Elzubair, Q. A., Sharif, E. A. M., & Ibrahim, W. N. (2024). Curcumin as a novel therapeutic candidate for cancer: can this natural compound revolutionize cancer treatment? Frontiers in Oncology, 14, 1438040. https://doi.org/10.3389/fonc.2024.1438040

Bertucci, A., Bertucci, F., & Gonçalves, A. (2023). Phosphoinositide 3-kinase (PI3K) inhibitors and breast cancer: An overview of current achievements. Cancers (Basel), 15(5), 1416. https://doi.org/10.3390/cancers15051416

Khan, H., Ullah, H., & Others. (2023). The role of curcumin in cancer: Focus on the PI3K/Akt pathway. Cancers, 16(8), 1554. https://doi.org/10.3390/cancers16081554

Li, H., Wen, X., Ren, Y., Fan, Z., Zhang, J., He, G., & Fu, L. (2024). Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions. Molecular Cancer, 23, 164. https://doi.org/10.1186/s12943-024-02072-1

Liu, G., Wang, T., Wang, T., Song, J., & Zhou, Z. (2013). Effects of apoptosis-related proteins caspase-3, Bax and Bcl-2 on cerebral ischemia rats. Biomedical Reports, 1, 861-867. https://doi.org/10.3892/br.2013.153

Lv, Z. D., Xu, J. W., Wang, L., Sun, D., & Zhang, S. (2014). Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo. Molecular Medicine Reports, 9(2), 559 564. https://doi.org/10.3892/mmr.2013.1672

Moawad, M., Nasr, G. M., Osman, A. S., & Shaker, E. S. (2023). Curcumin nanocapsules effect in apoptotic processes, gene expression, and cell cycle on Hep-G2 cell lines. International journal of immunopathology and pharmacology, 37, 3946320231176396. https://doi.org/10.1177/03946320231176396.

Mayo, B., Penroz, S., Torres, K., & Simón, L. (2024). Curcumin Administration Routes in Breast Cancer Treatment. International journal of molecular sciences, 25(21), 11492. https://doi.org/10.3390/ijms252111492

Ramos, J., & López, M. (2023). Targeting the PI3K pathway in breast cancer: Isoform¬-selective inhibitors, resistance mechanisms and therapeutic considerations. Journal of Translational Medicine, 21(1), 48. https://doi.org/10.1186/s12967-023-04841-w

Sarkar, E., Kotiya, A., Khan, A., Bhuyan, R., Misra, A., Raza, S. T., & Mahdi, A. A. (2024). The combination of curcumin and doxorubicin on targeting PI3K/AKT/mTOR signaling pathway: An in vitro and molecular docking study for inhibiting the survival of MDA-MB-231. In Silico Pharmacol, 12(2), 58. https://doi.org/10.1007/s40203-024-00231-2

Varkaris, A., de la Cruz, F., Martin, E., Norden, B., Chevalier, A., … & Getz, G. (2023). Allosteric PI3K α inhibition overcomes on target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations. Cancer Discovery, 14(2), 240 257. https://doi.org/10.1158/2159 8290.CD 23 0944

Varkaris, A., Pazolli, E., Gunaydin, H., Wang, Q., Pierce, L., Boezio, A. A., Bulku, A., DiPietro, L., Fridrich, C., Frost, A., Giordanetto, F., Hamilton, E. P., Harris, K., Holliday, M., Hunter, T. L., Iskandar, A., Ji, Y., Larivée, A., LaRochelle, J. R., Lescarbeau, A., … Kipp, D. R. (2024). Discovery and Clinical Proof-of-Concept of RLY-2608, a First-in-Class Mutant-Selective Allosteric PI3Kα Inhibitor That Decouples Antitumor Activity from Hyperinsulinemia. Cancer discovery, 14(2), 240–257. https://doi.org/10.1158/2159-8290.CD-23-0944

Vora, S. R., Juric, D., Kim, N., Mino Kenudson, M., Huynh, T., Costa, C., … Schrodder, G. (2014). PIK3CA mutation sensitizes breast cancer cells to synergistic therapy of PI3K inhibition and AMPK activation. Molecular Cancer Therapeutics, 13(5), 1032 1043. https://doi.org/10.1158/1535 7163.MCT 13 0572

Zhang, Y., Duan, J., Liu, Y., & Zhang, Y. (2024). Breaking a bottleneck for on-target toxicity: A mutant-selective PI3Kα inhibitor finally comes. The Innovation Medicine, 2(1), 100056. https://doi.org/10.59717/j.xinn-med.2024.100056

Zhu, J., Li, Q., Wu, Z., Xu, Y., & Jiang, R. (2024). Curcumin for treating breast cancer: A review of molecular mechanisms, combinations with anticancer drugs, and nanosystems. Pharmaceutics, 16(1), 79. https://doi.org/10.3390/pharmaceutics16010079

Zhu, J., Li, Q., Wu, Z., Xu, Y., & Jiang, R. (2024). Curcumin for treating breast cancer: A review of molecular mechanisms, combinations with anticancer drugs, and nanosystems. Pharmaceutics, 16(1), 79. https://doi.org/10.3390/pharmaceutics16010079.

Zoi, V., Kyritsis, A. P., Galani, V., Lazari, D., Sioka, C., Voulgaris, S., & Alexiou, G. A. (2024). The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway. Cancers, 16(8), 1554. https://doi.org/10.3390/cancers16081554

Downloads

Published

2025-11-25