Mitochondrial dysfunction pathway Drugs Functional mechanism Cell model References Energy metabolism Bcl-2 inhibitor ABT737 Disrupting Bcl2-dependent OXPHOS SKOV3 (cisplatin-sensitive) and SKOV3/DDP (cisplatin-resistant) [114 ] FDA-approved antibiotics Inhibit mitochondrial OXPHOS and/or biogenesis Ovarian cancer stem cells [115 ] IMT1B Targeting the human mitochondrial RNA polymerase and affecting the biogenesis of OXPHOS A2780 cells [116 ] Ivermectin Targeted lncRNA-EIF4A3-mRNA pathways A2780 and TOV-21G cells [117 ] Metabolites from invasive Caulerpa species Selectively inhibiting respiratory complex II activity OV2008 and C13 cells [118 ] Metformin-loaded PLGA-PEG nanoparticles OXPHOS SKOV-3 ovarian cells [119 ] Tigecycline Inhibiting translation by mitochondrial ribosome SW626 and SKOV-3 cells [120 ] Oxidative stress Amphiphilic doxorubicin Tumor- and mitochondria-selective deliveries of the anticancer drug The OVCAR-8 human ovarian carcinoma cell line and its doxorubicin-resistant derivative NCI/ADR-RES cell line [121 ] Induces an increased level of ROS generation PA-1 cells [122 ] Elesclomol sodium Accumulation of ROS RMG1 and OVCA432 cells [123 ] Epoxycytochalasin H Increased ROS level in cells A2780 cells [124 ] Eupatilin Reactive oxygen species (ROS) generation, calcium influx OV90 and ES2 cells [125 ] Extract of Persian Gulf Marine Mollusk (Turbo Coronatus) ROS-mediated mitochondrial targeting Human epithelial ovarian cancer cells [126 ] Isolinderalactone Mitochondrial superoxide-mediated pathways SKOV-3 and OVCAR-3 cells [127 ] Multifunctional tumor-targeted nanosized ultrasound contrast agents Consumed GSH and enhanced reactive ROS level A2780 and SKOV-3 cells [128 ] Olive leaf extract Increasing ROS and decreasing activity of ROS scavenging enzymes OVCAR-3 cells [129 ] Organoarsenical (PENAO) ROS production and mitochondrial depolarization OVCAR-3, SKOV-3, TOV112D, TOV21G, and EFO27 cells [130 ] Sideroxylin The induction of mitochondrial dysfunction and the activation of PI3K and MAPK signal transduction ES2 and OV90 cells [131 ] TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) spin label [C43 H43 N6 O2 Ir1 ·PF6 ]˙ (Ir-TEMPO1) and two TEMPO spin labels [C52 H58 N8 O4 Ir1 ·PF6 ]˙ (Ir-TEMPO2) Antiproliferative activity and antioxidant activity A2780 cells [132 ] Thiosemicarbazone iron chelators triapine and 2,2 Promote selective oxidation of mitochondrial Prx3 A2780 and OVCAR-3 cells [133 ] Transition metal complexes [Os(η 6 -p-cym)(Azpy-NMe2 )I]+ (p-cym=p-cymene, Azpy-NMe2 =2-(p-[dimethylamino] phenylazo)pyridine) Superoxide formed in the first step of O2 reduction in mitochondria A2780 cells [134 ] Cell apoptosis A hybrid drug dichloroacetate-platinum(II) [DCA-Pt(II)] Mitochondria-mediated apoptosis A2780 and A2780DDP cells [135 ] A monocationic, square-planar-platinum(II) complex [Pt(BDI(QQ))] Induces DNA damage, leading to p53 enrichment, mitochondrial membrane potential depolarization, and caspase-mediated apoptosis A2780 cells [136 ] Apomorphine Inducing caspase activation and mitochondrion-associated apoptosis ES2 and OV90 cells [137 ] AT-101/cisplatin Reducing some pivotal antiapoptotic proteins such as Bcl-2, HIF-1A, cIAP-1, and XIAP OVCAR-3 cells [138 ] Chaetomugilin J Enhancing apoptosis through inhibiting Pink1/Parkin-mediated mitophagy A2780 cells [139 ] Danusertib Danu induced mitochondria-dependent apoptosis and autophagy in a dose- and time-dependent manner C13 and A2780cp cells [140 ] Epothilones The induction of apoptosis via mitochondrial pathway OV-90 cells [141 ] Exosomal microRNAs Inhibitory effects on cells by blocking the cell cycle and activating mitochondria-mediated apoptosis signaling A2780 and SKOV-3 cells [142 ] Flex-Het Promoting mitochondrial-mediated apoptosis A2780 and OVCAR-3 cells [143 ] Gedunin isolated Triggered severe ROS generation leading to DNA damage and cell cycle arrest in G2/M phase thus inhibiting cell proliferation. ROS upregulation also led to mitochondrial stress and membrane depolarization, which eventually resulted in mitochondria-mediated apoptosis following cytochrome C release, caspase 9 and 3 activation, and PARP cleavage PA-1 and OVCAR-3 cells [144 ] Gentiopicroside Loss of MMP and induction of apoptosis SKOV-3 cells [145 ] Glycyrrhetinic acid rhodamine B benzyl amide 35 Triggered apoptosis A2780 cells [146 ] Hedyotis diffusa willd Induced through the mitochondria-associated apoptotic pathway A2780 cells [147 ] Jaceosidin Induction of apoptosis involving cytochrome c release from mitochondria to cytosol CAOV-3 cells [148 ] Lytic peptides (YX-1) Activating the mitochondria apoptotic pathway A2780 cells [149 ] Modified mitochondria-targeted chlorambucil compounds Effectively evading multidrug resistance resulting from cytosolic GST-μ upregulation by rapid E28 accumulation in mitochondria A2780 cells [150 ] Niclosamide Inducing mitochondrial uncoupling HCT116 p53+/+(H2B-GFP) and HCT116 p53−/−(H2B-RFP) ovarian cell lines [151 ] Nilotinib Reducing the viability of human ovarian cancer cells via mitochondrion-mediated apoptosis SKOV-3 cells [152 ] Piperine Release of mitochondrial cytochrome c to cytosol, activation of caspases 3 and 9 A2780 cells [153 ] Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs-cRGD) Upregulated the expression of p53 and promoted high levels of reactive oxygen species to induce the mitochondrial apoptosis pathway SKOV3 and SKOV3-DDP cells [154 ] Polyphyllin VII Induces mitochondrial apoptosis by regulating the PP2A/AKT/DRP1 signaling axis A2780 and SKOV-3 cells [155 ] Quercetin Induces mitochondrial-mediated apoptotic pathway PA-1 cells [156 ] rGO-Ag Reducing cell viability by mediating the generation of ROS, leaking lactate dehydrogenase, reducing mitochondrial membrane potential, and enhancing expression of apoptotic genes A2780 cells [157 ] RY-2f Upregulation of p21, cyclin B1, Bax, Bad and cleaved-PARP, and suppression of cyclin A, CDK2, and Bcl-2 A2780/CDDP cells [158 ] Sambucus nigra agglutinin Inducing apoptosis in ovarian cancer cells OAW-42 and SKOV-3 cells [159 ] Spiropyrazoline oxindoles compound 1a Mitochondria-mediated apoptosis and autophagy A2780 cells [160 ] STX140 and STX641 Depolarizing mitochondrial bioenergetics and activate caspase 3/7 A2780 cells [161 ] SW III-123 Activated both intrinsic and extrinsic apoptotic pathways SKOV-3 cells [162 ] Swerchirin Induction of mitochondrial apoptosis SKOV-3 cells [163 ] Z-Ligustilidein Triggering oxidative stress and inducing apoptosis OVCAR-3 cells [164 ] α -MangostinThe involvement of reactive oxygen species and mitochondrial-mediated apoptosis OVACAR-3 cells [165 ]166 ]167 ] 3,7,14,15-Tetra-acetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (TPEM) Promoting mitochondrial-mediated apoptosis OVCAR-3 and Caov-4 cells [168 ] Chrysophanol Inducing cell death and inhibiting invasiveness via mitochondrial calcium overload ES2 and OVCAR3 cells [169 ] Calcium overload Gentisyl alcohol Loss of mitochondrial membrane potential with calcium dysregulation ES2 and OV90 cells [170 ] Methiothepin Epolarization of the mitochondrial membrane and increased mitochondrion-specific Ca2+ levels and decreased ATP production and oxidative phosphorylation ES2 and OV90 cells [171 ] Autophagy BMI1 inhibitor (PTC-209) Targeting PINK1-PARK2-dependent mitochondrial pathway OVCAR4 and CP20 cells [172 ]
