Table 1.

Mitocan treatments, targets, and treatment effects. VDAC1—voltage-dependent anion channel 1; 2-DG—2-deoxy-D-glucose; 3-BPA—3-bromopyruvate; Benz—benserazide; STAT3—signal transducer and activator of transcription 3; HK—hexokinases; PBMCs—peripheral blood mononuclear cells; MMP—mitochondrial membrane potential; PKM2—pyruvate kinase M2 isoform; TPP—triphenylphosphonium; ROS—reactive oxygen species; PARP—poly (ADP-ribose) polymerase; NAC1—nucleus-accumbens-1; PYCR—pyrroline-5-carboxylate reductase; GSE—grape seed extract.

Mitochondrial Targets	Mitocan/Treatment Name	Treatment Effect	Clinical Trial Status	Reference
Hexokinase II	2-DG	Cytotoxicity, sensitization to prednisone	NT *	[73,74]
	3-BPA	Cytotoxicity, sensitization to prednisone	NT	[74,75,76]
	Lactobacillus casei peptidoglycan fragments (European Patent number 1217005)	Inhibition of entire metabolism of cancer tumour cells	NT	[77]
	Benz	Reduces glucose uptake, lactate production, and ATP levels, led to apoptosis	Phase 4 (NCT02741947))	[78]
	Rapamycin/siRNA downregulation of STAT3	Glycolysis inhibition, reduce glucose consumption	NT	[79]
	miR-134	Knockdown of HKII reduced glucose consumption leading to apoptosis	NT	[80]
	miR-218	Downregulation of HKII and apoptosis	NT	[81,82]
VDAC-1	VDAC1-based peptides Antp-LP4 and N-Ter-Antp	Highly effective in inducing cell death in leukemia patient PBMCs and cancer cell lines, but not healthy patient PBMCs	NT	[83,84,85]
	R-Tf-D-LP4 peptide	Targeted transferrin receptor in cancer cells, enhancing specificity of Antp-LP4 and N-Ter-Antp	NT	[86]
	VDAC-1 siRNA silencing	Decreased MMP and ATP levels, reducing tumour burden	NT	[87]
	Itraconazole	Inhibition of cell proliferation	NT	[88]
	Fenofibrate	Reprogramming of metabolism and apoptosis in oral carcinomas	NT	[89]
	Clotrimazole	Cytotoxicity, inhibition of glycolysis	NT	[90]
	Oroxillin A	Cytotoxicity, apoptosis, cell cycle arrest, and metastasis inhibition	NT	[91]
	Lonidamine	Cytotoxicity	NT	[91]
	Arsenites	Cytotoxicity	NT	[91]
	Steroid Analogs	Cytotoxicity	NT	[91]
Bcl-2 Family	Oblimersen	Downregulation of Bcl-2, synergy with other treatments	(G3139)	[92]
	PNT2258	Cell cycle arrest, apoptosis in non-Hodgkin’s lymphoma	Phase 2 (NCT02226965)	[93]
	SPC2996	Leukemic cell clearance, immune system activation and stimulation	Phase 2 (NCT00285103)	[94]
	ABT-737	Apoptosis in lymphoma and leukemia cell lines	NT	[95,96]
	ABT-263 (navitoclax) and ABT-199 (venetoclax)	Enhanced effects and specificity compared to ABT-737	Phase 2 (NCT03504644)Phase 2 (NCT03181126)	[97,98]
	Anthraquinone analog Compound 6	Binds Bcl-2, Mcl-2, and p-Mcl-2 leading to apoptosis induction	NT	[99]
	PKM2 siRNA silencing	Regulates oxidative stress induced apoptosis in a variety of cancers	NT	[100,101]
	TT-232	Translocation of PKM2 to nucleus to trigger apoptosis	Phase 2 (NCT00422786)	[102]
	miR-181b	Sensitize cancer cells to cisplatin	NT	[103]
	miR-630	Sensitize cancer cells to cisplatin	NT	[104]
Electron Transport Chain	Sorafenib (nexavar)	Inhibition of ATP synthase leading to Parkin-mediated apoptosis	Phase 3 (NCT00105443)	[105]
	MitoTam	Increased localization of tamoxifen to mitochondria, leading to increased specificity	Clinical trials to begin shortly	[106]
	TPP-Peptide Artemisinin-TPP Green titania ((G-TiO2-x) conjugated to TPP	Selectively kill anticancer cells	NT	[107,108,109]
	Reservatrol	Act as a pro-oxidant leading to cancer cell death	NT	[110,111]
	Metformin	Selective mitochondrial targeting, acts as an adjuvant with many cancer therapies	Phase 1 (NCT03477162)	[112,113,114]
	Pancratistatin analogues SVTH-6 and SVTH-7	Highly selective cytotoxicity on cancer cells in 2D and 3D culture models	NT	[115]
Oxidative Stress	MnTE-2-PyP5+	Enhance chemotherapeutic effect by mitochondrial environment modulation	NT	[116]
	Rotenone	Activates NOX2 resulting in increased ROS and cell death	NT	[117]
	Lonidamine	Cytotoxicity through ROS generation	NT	[118]
	Metformin	Additionally exert oxidative stress	Phase 1 (NCT03477162)	[112,113,114]
	PARP activation	Enhances ROS production leading to apoptosis	NT	[119]
	Curcumin analogue Compound A	Selective apoptosis through the generation of significant ROS in a variety of cancers	NT	[120]
	NAC1 silencing	Removal of oxidative stress defense mechanism, sensitization	NT	[121]
	PYCR1 and PYCR2 downregulation	Sensitizes cancer cells to ROS by inhibiting stress-response proteins	NT	[122]
Natural Health Products Targeting Mitochondria	Chrysin	Inhibits HKII binding to VDAC1 leading to apoptosis	NT	[123]
	Deguelin	Downregulates HKII leading to apoptosis	NT	[124]
	Halofuginone	Downregulates HKII	Phase 1 (NCT00027677)	[125]
	GSE	Targets complex III and depletes glutathione antioxidant leading to apoptosis in cancer	NT	[126]
	Dandelion root, long pepper, white tea, hibiscus, and lemongrass extracts	Highly effective induction of apoptosis and excessive ROS generation	Phase 1 (OCT1226, DRE)	[127,128,129,130]

* NT = not tested in clinical trials.