The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction
Abstract Background In cervical cancer (CC), Double C2 Like Domain Beta (DOC2B) functions as a metastatic suppressor. The present study aims to determine whether ectopic expression of DOC2B causes global metabolomic changes in extracellular vesicles (EVs) and corresponds with its tumor suppressive p...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-025-02218-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849314686752784384 |
|---|---|
| author | Sangavi Eswaran Roshan Mascarenhas Shama Prasada Kabekkodu |
| author_facet | Sangavi Eswaran Roshan Mascarenhas Shama Prasada Kabekkodu |
| author_sort | Sangavi Eswaran |
| collection | DOAJ |
| description | Abstract Background In cervical cancer (CC), Double C2 Like Domain Beta (DOC2B) functions as a metastatic suppressor. The present study aims to determine whether ectopic expression of DOC2B causes global metabolomic changes in extracellular vesicles (EVs) and corresponds with its tumor suppressive properties. Methods Using a retroviral method, we first ectopically expressed DOC2B in SiHa cells, which do not normally express DOC2B. Results We observed that ectopically expressed DOC2B significantly altered the global metabolite profile of EVs. Metabolomics identified significant enrichment of palmitoylcarnitine (PC) in EVs upon ectopic expression of DOC2B. We identified that SiHa and HeLa cells exhibited greater cytotoxicity to PC than gingival fibroblast, HaCaT, Cal27, and MCF7. PC treatment reduced the growth, proliferation, and migration of SiHa and HeLa cells, via increasing apoptosis and decreasing S-Phase cells. PC treatment resulted in morphological alterations, decreased length and number of filopodia, and expression of proteins related to cell cycle progression, proliferation, and the epithelial-to-mesenchymal transition. Further, PC treatment caused mitochondrial morphological changes, increased mitochondrial membrane potential, and decreased mtDNA content. The decreased GSH activity, glucose consumption rate, and lactate production upon PC treatment suggest that PC can induce metabolic reprogramming in CC cells. Increased oxidative stress, calcium overload, lipid droplet accumulation, mitochondrial lipotoxicity, and mitophagy suggest that PC can cause mitochondrial dysfunction. N-acetyl cysteine (NAC) treatment reversed the cytotoxic effect of PC, via decreasing lipid peroxidation rate and increasing GSH activity. PC treatment enhanced the cytotoxic effect of cisplatin in CC. Conclusion DOC2B restoration or the use of PC may be employed as a novel therapeutic approach for CC. |
| format | Article |
| id | doaj-art-1300455ebaa442e6937da47bb582e3dc |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-1300455ebaa442e6937da47bb582e3dc2025-08-20T03:52:24ZengBMCCell Communication and Signaling1478-811X2025-05-0123112410.1186/s12964-025-02218-8The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunctionSangavi Eswaran0Roshan Mascarenhas1Shama Prasada Kabekkodu2Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher EducationFaculty of Medical Sciences, Newcastle UniversityDepartment of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher EducationAbstract Background In cervical cancer (CC), Double C2 Like Domain Beta (DOC2B) functions as a metastatic suppressor. The present study aims to determine whether ectopic expression of DOC2B causes global metabolomic changes in extracellular vesicles (EVs) and corresponds with its tumor suppressive properties. Methods Using a retroviral method, we first ectopically expressed DOC2B in SiHa cells, which do not normally express DOC2B. Results We observed that ectopically expressed DOC2B significantly altered the global metabolite profile of EVs. Metabolomics identified significant enrichment of palmitoylcarnitine (PC) in EVs upon ectopic expression of DOC2B. We identified that SiHa and HeLa cells exhibited greater cytotoxicity to PC than gingival fibroblast, HaCaT, Cal27, and MCF7. PC treatment reduced the growth, proliferation, and migration of SiHa and HeLa cells, via increasing apoptosis and decreasing S-Phase cells. PC treatment resulted in morphological alterations, decreased length and number of filopodia, and expression of proteins related to cell cycle progression, proliferation, and the epithelial-to-mesenchymal transition. Further, PC treatment caused mitochondrial morphological changes, increased mitochondrial membrane potential, and decreased mtDNA content. The decreased GSH activity, glucose consumption rate, and lactate production upon PC treatment suggest that PC can induce metabolic reprogramming in CC cells. Increased oxidative stress, calcium overload, lipid droplet accumulation, mitochondrial lipotoxicity, and mitophagy suggest that PC can cause mitochondrial dysfunction. N-acetyl cysteine (NAC) treatment reversed the cytotoxic effect of PC, via decreasing lipid peroxidation rate and increasing GSH activity. PC treatment enhanced the cytotoxic effect of cisplatin in CC. Conclusion DOC2B restoration or the use of PC may be employed as a novel therapeutic approach for CC.https://doi.org/10.1186/s12964-025-02218-8Cervical cancerDOC2BPalmitoyl carnitineLipotoxicityReactive oxygen speciesMitochondria |
| spellingShingle | Sangavi Eswaran Roshan Mascarenhas Shama Prasada Kabekkodu The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction Cell Communication and Signaling Cervical cancer DOC2B Palmitoyl carnitine Lipotoxicity Reactive oxygen species Mitochondria |
| title | The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction |
| title_full | The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction |
| title_fullStr | The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction |
| title_full_unstemmed | The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction |
| title_short | The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction |
| title_sort | ester derivative palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction |
| topic | Cervical cancer DOC2B Palmitoyl carnitine Lipotoxicity Reactive oxygen species Mitochondria |
| url | https://doi.org/10.1186/s12964-025-02218-8 |
| work_keys_str_mv | AT sangavieswaran theesterderivativepalmitoylcarnitineabrogatescervicalcancercellsurvivalbyenhancinglipotoxicityandmitochondrialdysfunction AT roshanmascarenhas theesterderivativepalmitoylcarnitineabrogatescervicalcancercellsurvivalbyenhancinglipotoxicityandmitochondrialdysfunction AT shamaprasadakabekkodu theesterderivativepalmitoylcarnitineabrogatescervicalcancercellsurvivalbyenhancinglipotoxicityandmitochondrialdysfunction AT sangavieswaran esterderivativepalmitoylcarnitineabrogatescervicalcancercellsurvivalbyenhancinglipotoxicityandmitochondrialdysfunction AT roshanmascarenhas esterderivativepalmitoylcarnitineabrogatescervicalcancercellsurvivalbyenhancinglipotoxicityandmitochondrialdysfunction AT shamaprasadakabekkodu esterderivativepalmitoylcarnitineabrogatescervicalcancercellsurvivalbyenhancinglipotoxicityandmitochondrialdysfunction |