Table 4.

Antineoplastic activity of cyclitols in other cancers.

Type of Cancer	Study	Clinical Status	Cyclitol	Results
Prostate	Shamsuddin et al. (1995) [62]	PC-3 human prostate cells	IP6	Significant growth inhibition in 1 mM IP6 concentration after 24 h, and in 0.1 mM IP6 after 72 h Significant decrease in DNA synthesis after 3 h in 1 mM IP6 concentration Increased expression of HLA-1 class antigen in 1 mM IP6 and in 5 mM IP6 Significant increase in prostatic acid activity
Prostate	Sharma et al. (2003) [64]	Mouse prostate (TRAMP-C1) cells	IP6	The cell treatment with 1–4 mM of IP6 resulted in significant cell growth inhibition, increased cell death, and increased apoptosis IP6, at a concentration of 1–4 mM, induced G0–G1 phase arrest of the treated cells
Prostate	Singh et al. (2004) [65]	DU145 cells injected into nude mice	IP6	Significant reduction in tumor weight in mice treated with 2% of IP6 Decreased proliferation index and increased apoptotic index in IP6-treated cells (1–2% IP6) Inhibition of microvessel density in prostate tumor xenografts
Prostate	Lin et al. (2013) [63]	PC-3 and DU145 cells	d-pinitol	Significant decrease in cell migration and invasion after treatment with 3–30 mM d-pinitol Significant decrease in integrin αvβ3 expression after treatment with 3–30 mM d-pinitol Significant decrease in the levels of p-FAK a p-p65 and in the activity of c-Src kinase and NF-κβ luciferase after d-pinitol treatment
Pancreas	Somasundar et al. (2004) [66]	MIAPACA and PANC1 pancreatic cancer cell lines	IP6	Significant growth inhibition of cancer cells in all concentrations of IP6 Increased apoptotic rate in MIAPACA in 2.5 mM of IP6 and in PANC1 in 5 mM of IP6
Pancreas	McMillan et al. (2007) [67]	PANC1 and MIAPACA	IP6	Significant reduction of proliferation in the IP6-treated group (synergistic effect with catechin, after 48 and 72 h incubation) Synergistic effect with catechin in increasing apoptosis (alone IP6 did not induce a statistically significant reduction) Significant reduction of the VEGF level in IP6-treated cells (synergistic effect with catechin)
Liver	Lee et al. (2005) [68]	Rat treated with DEN	IP6 and Ins	Significant reduction in preneoplastic lesions in every experimental group (synergistic effect noted between IP6 and Ins) Significant increase in glutathione-S-transferase activity and a significant decrease in catalase activity in every experimental group (a synergistic effect between IP6 and Ins was noted) Significantly lower level of lipid peroxidation in experimental groups
Liver	Nishino (2009) [69]	Patients with chronic viral hepatitis and cirrhosis	MI	81% inhibition of liver cancer in the experimental group compared to controls
Osteosarcoma	Ren et al. (2017) [70]	In vitro (K7M2 and MG63.3 cells) and in vivo trials (mice with injected K7M2 cells)	IP6	Treatment of K7M2 cells with 0.3 mM IP6 and MG63.3 cells with 4 mM of IP6 resulted in 50% proliferation inhibition Inhibition of cancer cell growth In each line, exposure to 5 mM of IP6 for 6 h resulted in a significantly increased level of caspase 3/7 In the PuMA model, IP6 treatment of both K7M2/GFP and MG63.3/GFP resulted in markedly inhibited metastatic outgrowth in lung tissue IP6 treatment (60 mg/kg) of mice injected with K7M2 cells resulted in significantly higher survival rates (120 days versus 72 days) but did not influence the osteosarcoma primary tumor growth rate
Melanoma	Khurana et al. (2018) [71]	Case report	IP6 + Ins	Complete clinical and radiological remission after three years of treatment (primary patients diagnosed with stage IIIB melanoma had two reoccurrences of melanoma)