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. 2020 Nov 26;21(23):8988. doi: 10.3390/ijms21238988

Table 2.

Antineoplastic activity of cyclitols in breast tumors.

Study Clinical status Cyclitol Results
Shivapurkar et al. (1995) [29] MUN-induced rat mammary cancer IP6

  • Significant reduction of mammary tumor incidence at both 11 and 32 weeks of the experiment
Vucenik et al. (1995) [30] DMBA-induced rat mammary cancer IP6;
Ins;
IP6 + Ins

  • Significant reduction of tumor incidence in a group treated with: IP6 (p = 0.02), Ins (p < 0.05), or IP6 and Ins (p < 0.05) compared to controls

  • 58% reduction of tumor multiplicity in IP6 + Ins group compared to controls (1.8 ± 0.1 versus 3.1 ± 0.3, respectively) (p < 0.05)
Shamsuddin et al. (1996) [32] Human breast cancer cell lines MDA-MB-231 and MCF-7 IP6

  • Dose-dependent growth inhibition of both cell lines, suppression of DNA synthesis

  • Increased expression of lactalbumin (associated with luminal cell differentiation) up to 22-fold compared to controls
El-Sherbiny et al. (2001) [33] Human breast cancer cell lines MDA-MB-231 and MCF-7 IP6

  • Treatment with IP6 decrease S phase and arrest cells in the G0/G1 phase

  • Significant decrease in the percentage of Ki-67 expression in IP6-treated cells (p < 0.01)
Tantivejkul et al. (2003) [34] Human breast cancer cell line: MDA-MB-231 IP6

  • 65% reduction of cell adhesion of IP6-treated cells to fibronectin (p = 0.002), and 37% reduction of cell adhesion to collagen (p = 0.005)

  • Reduced number of migrating cells and the distance of cell migration (p < 0.001)

  • Absence of lamellipodia structure in IP6-treated cells (p = 0.001)

  • IP6 treatment inhibited MMP-9 secretion (p = 0.006)
Tantivejkul et al. (2003) [35] Human breast cancer cell line: MDA-MB-231 IP6

  • Decreased expression of integrin heterodimers: alpha2beta1 (collagen receptor), alpha5beta1 (fibronectin receptor) and alpha5beta3 (vitronectin receptor) (p < 0.005)
Tantivejkul et al. (2003) [37] MCF-7, MDA-MB 231 and adriamycin-resistant MCF-7 (MCF-7/Adr) human breast cell lines IP6

  • MCF-7/Adr was the most sensitive cell line for IP6 treatment (IC50 of 1.26 mM), while MCF-7 cell line was the least sensitive one (IC50 = 4.18 mM)

  • Synergism effect of growth suppression when IP6 was administered prior to adriamycin (especially against MCF-7 cells (p < 0.0001)

  • Synergism with tamoxifen in all three lines
Vucenik et al. (2005) [36] MCF-7 human breast cancer cell line IP6

  • 3.1-fold increased expression of antiproliferative PKCδ (p = 0.0002)

  • Decrease in Erk1/2 and Akt activity (p < 0.05)

  • Increased p27Kip1 and marked reduction of pRb phosphorylation (p < 0.05)
Bačić et al. (2010) [39] Ductal invasive breast cancer during FEC chemotherapy protocol IP6

  • Patients treated with IP6 and Inositol had a significantly higher quality of life than patients from the placebo group, significantly higher functional score compared to the placebo group (87.9 versus 56.3; p = 0.0003), and lesser side symptoms (13.5 versus 33.8 on the symptomatic scale; p = 0.04)

  • No leukocyte or platelet drop in the IP6- and inositol-treated group (the drop in leukocytes and platelets was significant in the control group)
Pasta et al. (2015) [42] Mammographic breast density (premenopausal women) MI

  • Significant reduction of breast density in the MI group compared to the placebo group (60% versus 9%), p < 0.001

  • Significant pain reduction after treatment in 13 out of 15 (86.7%) women with high breast density
Pasta et al. (2016) [44] Breast fibroadenomas MI

  • Reduction of fibroadenoma median volume for 17.86% (p = 0.005) versus 5.96% in the placebo group (p = n.s.)

  • 38.88% of patients from the MI arm had a reduction of fibroadenoma volume, compared to 17.85% in the placebo arm

  • No patients from the placebo or experimental arm showed signs of worsening
Dinicola et al. (2016) [38] Human breast cancer cell lines MDA-MB-231 and ZR-75 Inositol

  • Reduction of PI3K activity by 40% (p < 0.001) and phosphorylated Akt by 35% (p < 0.05) after Ins treatment, compared to controls

  • Ins treatment increased by 7-fold the level of E-cadherin (p < 0.001) and doubled the level of β-catenin (p < 0.01), compared to controls

  • Decreased SNAI1 expression after Ins treatment (p < 0.001)

  • Ins treatment reduced both motility (p < 0.001) and invasiveness (p < 0.05) of breast cancer cells

  • No detectable formation of lamellipodia and filopodia was observed in Ins-treated cells

  • Cytoskeleton stabilization in Ins-treated cells.
Proietti et al. (2017) [41] Ductal breast cancer stages II‒III postoperative (lumpectomy); during polychemotherapy CMF IP6

  • Significant reduction of chemotherapy side effects in IP6-treated group compared to controls (12 ± 10 versus 45.81 ± 10.0; p ≤ 0.001)

  • No leukocytes or platelets drop in the IP6-treated group (reduction of leukocytes and platelets was significant in the control group)

  • One-third the number of postponed chemotherapy cycles in the IP6-treated group compared to the control group

  • Significant improvement of quality of life in the IP6-treated group

  • Significant improvement of functional status in the IP6-treated group