LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer

Cakici, Cagri; Daylan, Benay; Unluer, Ruveyde Safiye; Emekli-Alturfan, Ebru; Ayla, Sule; Gozel, Hilal Eren; Yigit, Pakize; Dokgoz, Elif Yavuz; Yigitbasi, Turkan

doi:10.7150/jca.86283

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J Cancer 2024; 15(3):590-602. doi:10.7150/jca.86283 This issue Cite

Research Paper

LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer

Cagri Cakici^1✉, Benay Daylan², Ruveyde Safiye Unluer³, Ebru Emekli-Alturfan⁴, Sule Ayla⁵, Hilal Eren Gozel⁶, Pakize Yigit⁷, Elif Yavuz Dokgoz⁸, Turkan Yigitbasi¹

1. Department of Biochemistry, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey, 34815.
2. Department of Histology and Embryology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey, 34815.
3. Graduate School of Health Sciences, Istanbul Medipol University, Istanbul, Turkey, 34815.
4. Department of Basic Medical Sciences, Faculty of Dentistry, Marmara University, Istanbul, Turkey, 34857.
5. Department of Histology and Embryology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey, 34720.
6. Department of Medical Biology and Genetics, Faculty of Medicine, Istanbul Okan University, Istanbul, Turkey, 34959.
7. Department of Biostatistics and Medical Informatics, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey, 34815.
8. Department of Biochemistry, Faculty of Pharmacy, Istinye University, Istanbul, Turkey, 34010.

Citation:

Cakici C, Daylan B, Unluer RS, Emekli-Alturfan E, Ayla S, Gozel HE, Yigit P, Dokgoz EY, Yigitbasi T. LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer. J Cancer 2024; 15(3):590-602. doi:10.7150/jca.86283. https://www.jcancer.org/v15p0590.htm

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Abstract

Increased LDH-A activity promotes tumor growth, migration, invasion, and metastasis. This study aimed to investigate the effects of the combination of LDH-A inhibitor and Docetaxel on apoptosis and epithelial-mesenchymal transition (EMT) in the murine prostate cancer (PCa) model.

The prostate cancer murine model was developed subcutaneously in 50 male B57CL/6 mice using the Tramp-C2 prostate cancer cell line. From the tumor tissue samples, apoptosis analysis was performed using TUNEL staining, and EMT was investigated using western blot and qPCR. Hematoxylin-eosin staining (HE) and Periodic acid-Schiff staining were used to histopathologically examine liver and kidney tissues.

Lactate levels revealed that the Warburg effect was reversed with the LDH-A inhibitor. Both serum and tumor tissue apoptosis increased, and tumor sizes reduced in PCa+LDH-A inhibitor + Docetaxel treatment groups (p<0.05). The combination of LDH-A inhibitor and Docetaxel inhibited EMT mechanism by causing a decrease in Snail, Slug, Twist, and HIF-1α expressions as well as a decrease in N-cadherin and an increase in E-cadherin levels.

Reprogramming glucose metabolism with an LDH-A inhibitor can increase the effectiveness of Docetaxel on apoptosis and metastasis mechanisms in PCa.

Keywords: Prostate cancer, Apoptosis, EMT, LDH-A inhibitor, Warburg effect

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APA

Cakici, C., Daylan, B., Unluer, R.S., Emekli-Alturfan, E., Ayla, S., Gozel, H.E., Yigit, P., Dokgoz, E.Y., Yigitbasi, T. (2024). LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer. Journal of Cancer, 15(3), 590-602. https://doi.org/10.7150/jca.86283.

ACS

Cakici, C.; Daylan, B.; Unluer, R.S.; Emekli-Alturfan, E.; Ayla, S.; Gozel, H.E.; Yigit, P.; Dokgoz, E.Y.; Yigitbasi, T. LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer. J. Cancer 2024, 15 (3), 590-602. DOI: 10.7150/jca.86283.

NLM

CSE

Cakici C, Daylan B, Unluer RS, Emekli-Alturfan E, Ayla S, Gozel HE, Yigit P, Dokgoz EY, Yigitbasi T. 2024. LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer. J Cancer. 15(3):590-602.

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