Application of natural micromolecule HEC-23 to preparation of medicine for promoting lysosome mediated cell death
A technology of small molecular compounds and lysosomes, applied in the field of chemical biology, can solve the problems of lack of apoptosis mechanism and tumor drug resistance, and achieve the effect of reducing the dose of chemotherapy drugs, reducing the dose of cisplatin, and improving the effect of chemotherapy
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Embodiment 1
[0042] Example 1: HEC-23 induces cell death of human cervical cancer cell line (HeLa)
[0043] Adding 10 μM HEC-23 to cultured human HeLa cells for 3 hours, it was found that HEC-23 specifically increased LAMP-1-positive lysosomes, but did not significantly affect Rab5-positive early endosomes and Rab7-positive endosomes. Late endosomes, such as attached figure 1 shown.
Embodiment 2
[0045] HeLa cells were transfected with mCherry-LAMP1 plasmid to specifically mark lysosomes, treated with 10 μM HEC-23 for 3 hours, then added 1 μM lysosome acidified fluorescent probe LysoSensor and stained for 30 minutes. Later, it was found that the LysoSensor staining in the enlarged lysosomes of HEC-23 was significantly reduced, indicating that the enlarged lysosomes could not be acidified normally, as shown in the attached figure 2 shown.
Embodiment 3
[0047] BODIPY pepstatin A can specifically bind to the activated lysosomal hydrolase cathepsin D, indicating the maturation of lysosomes. After HeLa cells were treated with 10 μM HEC-23 for 3 hours, BODIPY pepstatin A staining was added for 30 minutes, and the staining of BODIPYpepstatin A in the enlarged lysosomes of HEC-23 was significantly reduced, indicating that the enlarged lysosomes could not mature. image 3 shown.
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