Investigator

Joaquín Alberto Padilla-Flores

Research assistant · Universidad Nacional Autónoma de México Facultad de Estudios Superiores Iztacala, Laboratorio de Control Metabólico

About

JAPJoaquín Alberto P…
Papers(1)
Synergistic celecoxib…
Collaborators(4)
Rebeca López-MarureSara Rodríguez-Enríqu…Tuuli KaambreDiana Xochiquetzal Ro…
Institutions(3)
Unknown InstitutionInstituto Nacional de…National Institute Of…

Papers

Synergistic celecoxib and dimethyl-celecoxib combinations block cervix cancer growth through multiple mechanisms

Objective The synergistic inhibitory effect of celecoxib (CXB) and dimethyl-celecoxib (DMC) plus paclitaxel (PA) or cisplatin (CP) on human cervix HeLa and SiHa cells was assessed at multiple cellular levels in order to elucidate the biochemical mechanisms triggered by the synergistic drug combinations. Methods The effect of CXB (5 μM)/CP (2 μM) or CXB (5 μM)/PA (15 μM) and DMC (15 μM)/CP (5 μM) or DMC (15 μM)/PA (20 μM) for 24 h was assayed on cancer cell proliferation, energy metabolism, mitophagy, ROS production, glycoprotein-P activity, DNA stability and apoptosis/necrosis. Results Drug combinations synergistically decreased HeLa and SiHa cell proliferation (>75%) and arrested cellular cycle by decreasing S and G2/M phases as well as the Ki67 content (HeLa) by 7.5–30 times. Cell viability was preserved (>90%) and no apparent effects on non-cancer cell growth were observed. Mitochondrial and glycolytic protein contents (44–95%) and ΔΨm (45–50%) in HeLa cells and oxidative phosphorylation and glycolysis fluxes (70–90%) in HeLa and SiHa cells were severely decreased, which in turn promoted a drastic fall in the ATP supply (85–88%). High levels of mitophagy proteins in HeLa cells and active mitochondrial digestion in HeLa and SiHa cells was observed. Mitochondrial fission and microtubule proteins were also affected. Intracellular ROS content (2–2.3-fold) and ROS production was stimulated (2.3–4 times), whereas content and activity of glycoprotein-P (45–85%) were diminished. DNA fragmentation was not observed and apoptosis/necrosis was not detected suggesting that cell death could be mainly associated to mitophagy induction. Conclusions CXB or DMC combination with canonical chemotherapy may be a promising chemotherapy strategy against cervical cancer growth, because it can selectively block multiple cell processes including inhibition of energy pathways and in consequence ATP-dependent processes such as cell proliferation, glycoprotein-P activity, ROS production and mitophagy, with no apparent effects on non-cancer cells.

6Works
1Papers
4Collaborators

Positions

2022–

Research assistant

Universidad Nacional Autónoma de México Facultad de Estudios Superiores Iztacala · Laboratorio de Control Metabólico

2018–

Becario/ Research assistant

Instituto Nacional de Cardiología Ignacio Chávez · Biochemestry

Education

2023

Master in Chemobiological Sciences

Instituto Politécnico Nacional Escuela Nacional de Ciencias Biológicas

2020

Biologist

Universidad Nacional Autónoma de México Facultad de Estudios Superiores Iztacala

Keywords
Cancer metabolismCancercancer reprogramming metabolismNitrogen metabolismWarburg EffectOncologyTumor progressionMitochondrial metabolism