Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells
L Sánchez-Sánchez1,2, M L Escobar3, J Sandoval-Ramírez4
1Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 09230, Mexico, DF, Mexico. luisss@unam.mx.
Abstract:
The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to induce apoptosis and autophagy in cervical cancer cells are reported. We ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin suggests that the anti-proliferative activity of this steroid is not always dependent on the cell cycle. Cytotoxic activity was evaluated by detection of the lactate dehydrogenase enzyme in supernatants from tumor cell cultures treated with the steroid. Glucolaxogenin exhibited null cytotoxic activity. With respect to the apoptotic activity, the generation of apoptotic bodies, the presence of active caspase-3 and annexin-V, as well as the DNA fragmentation observed in all tumor lines after treatment with glucolaxogenin suggests that this compound does indeed induce cell death by apoptosis. Also, a significantly increased presence of the LC3-II, LC3 and Lamp-1 proteins was evidenced with the ultrastructural existence of autophagic vacuoles in cells treated with this steroidal glycoside, indicating that glucolaxogenin also induces autophagic cell death. It is important to note that this compound showed no cytotoxic effect and did not affect the proliferative capacity of mononuclear cells obtained from normal human peripheral blood activated by phytohaemagglutinin. Thus, glucolaxogenin is a compound with anti-proliferative properties that induces programmed cell death in cancer cell lines, though it is selective with respect to normal lymphocytic cells. These findings indicate that this glycoside could have a selective action on tumor cells and, therefore, be worthy of consideration as a therapeutic candidate with anti-tumor potential.
Insights
Glucolaxogenin inhibits cervical cancer cell proliferation and induces programmed cell death via apoptosis and autophagy. This compound is selective, showing no cytotoxic effects on normal human lymphocytes, suggesting therapeutic potential.
Area of Science:
- Pharmacology
- Cancer Biology
- Cell Biology
Background:
- Cervical cancer remains a significant global health challenge.
- Novel therapeutic agents with selective action against cancer cells are urgently needed.
- Glucolaxogenin, a steroidal glycoside, has shown potential in preliminary studies.
Purpose of the Study:
- To investigate the antiproliferative and cytotoxic effects of glucolaxogenin on cervical cancer cell lines.
- To determine if glucolaxogenin induces apoptosis and autophagy in these cancer cells.
- To assess the selectivity of glucolaxogenin towards normal human lymphocytes.
Main Methods:
- Dose-dependent proliferation assays using HeLa, CaSki, and ViBo cervical cancer cells.
- Cell cycle analysis to understand the mechanism of antiproliferative activity.
- Lactate dehydrogenase (LDH) assay to evaluate cytotoxic activity.
- Assessment of apoptosis markers (caspase-3, annexin-V, DNA fragmentation) and autophagy markers (LC3-II, LC3, Lamp-1).
- Evaluation of effects on phytohaemagglutinin-activated normal human peripheral blood mononuclear cells.
Main Results:
- Glucolaxogenin demonstrated dose-dependent inhibition of cervical cancer cell proliferation.
- The compound induced apoptosis, evidenced by apoptotic bodies, active caspase-3, annexin-V binding, and DNA fragmentation.
- Glucolaxogenin also induced autophagic cell death, indicated by increased LC3-II, LC3, and Lamp-1 proteins and autophagic vacuoles.
- No cytotoxic activity or inhibition of proliferation was observed in normal human lymphocytes.
- Antiproliferative effects were not consistently dependent on cell cycle phase.
Conclusions:
- Glucolaxogenin exhibits significant antiproliferative properties against cervical cancer cell lines.
- The compound effectively induces programmed cell death through both apoptosis and autophagy.
- Glucolaxogenin displays selectivity, sparing normal lymphocytes from cytotoxic effects.
- These findings highlight glucolaxogenin as a promising therapeutic candidate for anti-tumor applications in cervical cancer.
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