Increasing cancer cell sensitivity to chemotherapy by amending aberrant metabolism using
plant extracts represents a promising strategy to lower chemotherapy doses while retaining the same
therapeutic outcome. Here, we incubated HepG2 cells with four plant extracts that were selected
based on an earlier assessment of their cytotoxicity, viz asparagus, green tea, rue, and avocado,
separately, before treatment with doxorubicin. MTT assays elucidated a significant decrease in
doxorubicin-IC50 following HepG2 incubation with each extract, albeit to a variable extent. The
investigated extract’s ultra-performance liquid chromatography and gas chromatography coupled
with mass spectrometry (UPLC/MS and GC/MS) revealed several constituents with anticancer
activity. Biochemical investigation displayed several favorable effects, including the inhibition of
hypoxia-inducible factor1 (HIF1 ), c-Myc, pyruvate kinase-M2 (PKM2), lactate dehydrogenase-
A (LDH-A), glucose-6-phosphate dehydrogenase (G6PD), and glutaminase by asparagus and rue
extracts. To less extent, HIF1 , c-Myc, PKM2, and LDH-A were partially inhibited by green tea
extract, and HIF1 and glutaminase activity was inhibited by avocado oil. Undesirably, green tea
extract increased glutaminase; avocado oil rose c-Myc, and both increased G6PD. In conclusion, our
study confirms the potential cytotoxic effects of these plant extracts. It highlights a strong association
between the ability of asparagus, green tea, rue, and avocado to sensitize HepG2 cells to doxorubicin
and their power to amend cell metabolism, suggesting their use as add-on agents that might aid in
clinically lowering the doxorubicin dose. |
