Uncovering the role of modified citrus pectin in cancer
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2022
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Nuclear Medicine and Biology
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Background: Modified citrus pectin (MCP) is a polysaccharide
consisting of galacturonic acid with anti-cancer activity that can act
synergistically with other treatments to reduce tumor growth, stimulate
programmed cell death and reduce the number of metastases.
In addition, MCP prevents acute and severe renal syndromes caused
by radiation/chemotherapy. All of these effects were reported to be
due to MCP ability to specifically inhibit Galectin-3 protein functions.
Aims: The aim of this work was to evaluate the anticancer effect
of MCP in a Balb/c nude mice xenograft model of ovarian cancer.
Methods: The human ovary cancer cell line, SKOV-3, was subcutaneously
injected in Balb/c nude mice and tumor growth was monitored
daily with a caliper. When tumors reached 250-300 mm3, 20
mg/kl of MCP was administered intravenously (I.V.) in a daily based
for 21 days. Tumor growth and mice weight were monitored daily.
Additionally, MCP was radiolabeled with 99m-technetium (99m-Tc)
with the incubation of MCP (2.5 mg) in saline with SnCl2 (4 mg/
ml), HCl (0.01 M), NaOH (0.01 M) and 99mTc (129,5 MBq) at pH=7
for 30 min. The radiochemical purity was determined by iTLC-SG
with acetone and ethanol/NH3/H2O (1:2:5). 99mTc-MCP (37 MBq)
was administrated I.V. in Balb/C nude mice bearing SKOV-3 tumors
and after 1, 2 and 4 hours, SPECT/CT image was acquired (Albira SI
Buker). Ex-vivo biodistribution studies were performed after the I.V.
injection of 10 MBq of 99mTc-MCP for 1-hour. The % of injected dose per gram (%ID/g) of tissues of interest was calculated. The tumors
were removed, fixed, cut and used for autoradiography studies and
stained with hematoxylin and eosin (H&E) to verify hypoxic regions.
Results: The I.V. administration of MCP was able to significantly
reduce SKOV-3 tumor growth (52% tumor volume reduction) in
comparison with the non-treated group, after 21 of treatment. Our
biodistribution studies showed that 99mTc-MCP was mainly found
in kidneys, bladder and liver of mice (%ID/g = 12.25, 38.57 and 5.71,
respectively), and was able to reach the tumor (%ID/g = 0.765 ±
0.045) 1-hour after I.V. administration. 99mTc-MCP accumulation in
the tumor site was visualized by μSPECT/CT imaging 1 hour after I.V.
administration. The autoradiography and stained (H&E) study demonstrated
a correlation between MCP and regions of tumor necrosis.
Because of MCP high accumulation in kidneys, renal toxicity was also
evaluated. We were able to find that MCP doesn’t induce renal toxicity
when administered in a daily base at a concentration of 20 mg/Kg.
Conclusion: In this work we demonstrated that a daily treatment
of MCP was able to reduce tumor growth of ovarian tumor xenografts
(SKOV-3 cells) without showing renal toxicity. We found too that
MCP can reach the tumor site, binding mainly in regions of necrosis.
However, other studies are needed to unravel the mechanisms of
action that act on the antitumor effect of MCP.
Como referenciar
SILVA, FABIO A. da; BERNARDES, EMERSON S. Uncovering the role of modified citrus pectin in cancer. Nuclear Medicine and Biology, v. 108-109, p. S176-S177, 2022. S1. DOI: 10.1016/S0969-8051(22)00371-7. Disponível em: http://repositorio.ipen.br/handle/123456789/33225. Acesso em: 26 Apr 2024.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.