An update on the effectiveness of metformin alone and with chemotherapy drugs on tumor cells

Al-Zahrani, Norah Saeed; Ali, Ehab M.M.; Kalantan, Abdulaziz A.; Zamzami, Mazin A.

doi:10.34154/2020-ejcs-0201-10-19/euraass

Cited by 1 publication

(1 citation statement)

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“…Increased mTOR signaling activity has been associated with prostate, brain, lung, bladder, and kidney cancers. The epidermal growth factor (EGF) is thought to be downstream of the mTOR pathway [31]. Another research study indicated that the treatment of SK-MEL-28 melanoma cells with PXT and MET for 24 h resulted in the activation of AMPK and the mTOR pathway downstream [32].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Protein-Induced Apoptosis and Autophagy in Human Hepatocytes Treated with Metformin and Paclitaxel In Silico and In Vitro

Al-Zahrani,

Zamzami,

Baghdadi

et al. 2023

Biomedicines

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Metformin and paclitaxel therapy offer promising outcomes in the treatment of liver cancer. Combining paclitaxel with metformin enhances treatment effectiveness and mitigates the adverse effects associated with paclitaxel alone. This study explored the anticancer properties of metformin and paclitaxel in HepG2 liver cancer cells, MCF-7 breast cancer cells, and HCT116 colon cancer cells. The results demonstrated that the combination of these agents exhibited a lower IC50 in the tested cell lines compared to paclitaxel monotherapy. Notably, treating the HepG2 cell line with this combination led to a reduction in the G0/G1 phase and an increase in the S and G2/M phases, ultimately triggering early apoptosis. To further investigate the interaction between the cellular proteins with paclitaxel and metformin, an in silico study was conducted using proteins chosen from a protein data bank (PDB). Among the proteins studied, AMPK-α, EGFRK, and FKBP12-mTOR exhibited the highest binding free energy, with values of −11.01, −10.59, and −15.63 kcal/mol, respectively, indicating strong inhibitory or enhancing effects on these proteins. When HepG2 cells were exposed to both paclitaxel and metformin, there was an upregulation in the gene expression of AMPK-α, a key regulator of the energy balance in cancer growth, as well as apoptotic markers such as p53 and caspase-3, along with autophagic markers including beclin1 and ATG4A. This combination therapy of metformin and paclitaxel exhibited significant potential as a treatment option for HepG2 liver cancer. In summary, the combination of metformin and paclitaxel not only enhances treatment efficacy but also reduces side effects. It induces cell cycle alterations and apoptosis and modulates key cellular proteins involved in cancer growth, making it a promising therapy for HepG2 liver cancer.

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Section: Discussionmentioning

confidence: 99%