Phenformin

Phenformin (Phenethylbiguanide) is an orally active biguanide hypoglycemic agent. Phenformin inhibits mitochondrial respiratory chain complex I, leading to an increased AMP/ATP ratio, activation of AMPK, and subsequent inhibition of the mTOR pathway, thereby suppressing cell proliferation, inducing apoptosis and autophagy. Phenformin inhibits cancer stem cells (CSCs) and possesses potent antitumor potential^[1][2][3][4]. In Vitro:Phenformin induces G0/G1 cell cycle arrest, reduces the proportion of S phase in a dose-dependent manner, inhibits CDK4 and D glycine, and activates p21 protein in SKOV3, IGROV-1 and Hey ovarian cancer cell lines^[1].
Phenformin acts synergistically with SCH772984 (HY-50846) to inhibit proliferation, induce apoptosis, and completely suppress the mTOR signaling pathway in NF1-mutant melanoma cells^[1].
Combination treatment with Phenformin and Temozolomide (HY-17364) exerts a synergistic effect on the death of glioblastoma stem cells, thereby enhancing the anti-tumor activity of Phenformin and reducing its required administration concentration^[1].
Phenformin (0.5-5 mM; 24-72 h) reduces the viability and promotes apoptosis of SET2 JAK2^V617F cells, with corresponding IC₅₀ values of 2 mM, 1.79 mM and 0.79 mM at 24 h, 48 h and 72 h, respectively^[2].
Phenformin (2 mM; 12-48 h) inhibits the proliferation of human cholangiocarcinoma cell lines RBE and Huh28 in a time-dependent manner, with significant effects observed at 12, 24 and 48 h^[3].
Phenformin (2 mM; 10 days) inhibits the colony-forming ability of human cholangiocarcinoma cell lines RBE and Huh28^[3].
Phenformin (2 mM; 24 h) induces apoptosis in human cholangiocarcinoma cell lines RBE and Huh28 after 24 h of treatment^[3].
Phenformin (2 mM; 24 h) upregulates the mRNA expression of autophagy-related genes (BECN1, ATG5, ATG7) in human cholangiocarcinoma cell lines RBE and Huh28 after 24 hours of treatment^[3].
Phenformin (2 mM; 12-48 h) exerts a significantly stronger inhibitory effect on the viability of LKB1-knockdown RBE and Huh28 human cholangiocarcinoma cell lines than on cells transfected with negative control siRNA at 12, 24, and 48 h^[3]. In Vivo:Phenformin (40 mg/kg; i.p.; daily; 45 days) increases the percentages of LSK, myeloid progenitor, and multipotent progenitor populations but does not reduce disease burden in Jak2^V617F-knockin MPN mice^[2].
Phenformin (2 mM; intratumoral; every 4 days; 30 days) significantly inhibits RBE tumor volume in a subcutaneous cholangiocarcinoma xenograft mouse model^[3].