Prostate cancer remains one of the most common cancers amongst men worldwide and pressing for effective treatments is a perpetual need in the medical community. Cisplatin, a chemotherapy medication known for its effectiveness against various solid tumors, is renowned for its capacity to induce DNA damage and trigger cancer cell death. However, recent exploration in the field of cancer metabolism has shed light on how cisplatin might also exert influence over the cellular energetic landscape. A cutting-edge study published in the “Bratislavské lekárske listy” journal attempted to elucidate the intricacies behind cisplatin’s impact on ATP production pathways in prostate cancer cells. The study, entitled “Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells” (DOI: 10.4149/BLL_2024_013), probes the potential of autophagy inhibitors to modify the metabolic reactions of cells to cisplatin treatment – an avenue of research that might pave the way to optimally sync autophagy modulation with conventional chemotherapy.

The study conducted by Kratochvilova et al. published in the Bratisl Lek Listy (2024, Vol. 124, Issue 2, pp. 84-91) cast new light on the relationship between cellular metabolism, the role of autophagy, and the effectiveness of cisplatin in the context of prostate cancer. To set the stage for this discussion, let’s first unpack the scientific concepts harnessed in this research.

Autophagy: A Cellular Recycling Process

Autophagy is a biological process through which cells degrade and recycle cellular components. This self-eating mechanism grants cells the capacity to manage waste and maintain energy when under duress, such as nutrient deprivation or treatment-induced stress.

Cisplatin: A Double-edged Sword

The anticancer drug cisplatin is employed to address malignancies by inducing DNA damage; however, it’s understood that its effects extend into the metabolic processes of cancer cells, altering their energy production and nutrient utilization dynamics.

In their investigation, the researchers addressed how the prostate cancer cells – 22Rv1 and PC-3, each with uttering degrees of autophagy proficiency, and DU145 cells marked by dysfunctional autophagy – responded to cisplatin’s effects on ATP production. ATP or adenosine triphosphate serves as the primary energy currency within cells, synthesized chiefly through oxidative phosphorylation (OXPHOS) and glycolysis.

The Impact of Cisplatin on ATP Production

Intriguingly, the study revealed that ATP production via OXPHOS diminished significantly in 22Rv1 and PC-3 cells post-cisplatin treatment, while the glycolytic pathway of ATP generation experienced no notable change in 22Rv1 cells. This observation is pivotal, as it underscores a metabolic shift in prostate cancer cells’ attempt to cope with the effects induced by cisplatin.

The Curious Case of DU145 Cells

The cells with impaired autophagy, DU145, demonstrated a high sensitivity to cisplatin, concomitant with reduced levels of ATP production. This is indicative of a metabolically precarious situation where the absence of autophagy renders cells more susceptible to energy deprivation and, hence, to the cytotoxic impact of treatments like cisplatin.

Autophagy Inhibition: A Non-starter?

A central aspect of the research examined whether autophagy inhibitors, autophinib, and SAR405, could tweak cisplatin’s influence on ATP production. After short-term treatment (24 hours) with these inhibitors, the study observed no alteration in cisplatin’s impact on energy production in the cells considered. This suggests that a transient cessation of autophagy does not compound the metabolic effects of cisplatin treatment.

The study underlines the importance of amino acids as key players in cellular metabolism and survival under treatment-induced stress. With reference to the culture medium’s composition, levels of amino acids such as arginine and methionine significantly influenced cancer cell viability during cisplatin treatment. Particularly, a persistent defect in autophagy could modulate metabolic sensitivity through interference in arginine metabolism – a critical nexus point that could be decisive for cell fate under pharmacological stress.


1. Cisplatin Prostate Cancer Treatment
2. Autophagy Inhibition Cancer
3. ATP Production Cancer Metabolism
4. Cisplatin and Cellular Energy
5. Autophagy Inhibitors Oncology


The research by Kratochvilova and colleagues presents a dichotomous tale: while unveiling the metabolic influence of cisplatin, it concurrently evokes in us a reflection on the expectations cast onto the shoulders of autophagy inhibitors in cancer therapy. It’s an invitation to the medical and scientific communities to tread deeper into the metabolic mazes of cancer to unchain the potential of combinatorial therapies.

Such studies not only seed future research ventures but also serve as milestones marking our journey through an ever-expanding frontier of cancer treatments. As we journey onwards, the consolidation of our learnings will be imperative in formulating a multi-pronged attack on prostate cancer, one that is nuanced in its strategy and unrelenting in its pursuit of a cure.


1. Kratochvilova, M., Stepka, P., Raudenska, M., et al. (2024) “Short-term autophagy inhibition by autophinib or SAR405 does not alter the effect of cisplatin on ATP production in prostate cancer cells”, Bratislavské lekárske listy, 124(2), pp. 84-91. DOI: 10.4149/BLL_2024_013.
2. Amaravadi, R. K., Lippincott-Schwartz, J., Yin, X. M., et al. (2011) “Principles and Current Strategies for Targeting Autophagy for Cancer Treatment”, Clinical Cancer Research, 17(4), pp. 654-666.
3. Galluzzi, L., Senovilla, L., Vitale, I., et al. (2012) “Molecular mechanisms of cisplatin resistance”, Oncogene, 31(15), pp. 1869-1883.
4. White, E. (2012) “Deconvoluting the context-dependent role for autophagy in cancer”, Nature Reviews Cancer, 12(6), pp. 401-410.
5. Ding, Z.-B., Hui, B., Shi, Y.-H., et al. (2011) “Autophagy Inhibition Specifically Promotes Epithelial-Mesenchymal Transition and Invasion in RAS-Mutated Cancer Cells”, Autophagy, 7(6), pp. 669-678.

This article elaborated on the publication found in “Bratislavské lekárske listy,” with a focus on the exciting interplay between cisplatin treatment, autophagy, and ATP production within prostate cancer cells. Noteworthy is that the insights garnered from this study may not yet translate into immediate clinical implications, for the confluence of autophagy, metabolism, and pharmacology is a complex tapestry requiring further unraveling.