Estradiol and progesterone regulate proliferation and apoptosis in colon cancer

Abstract

Epidemiological studies describe estrogens as protectors in the development of colon cancer in postmenopausal women treated with hormone replacement therapy. However, the role of progesterone in colon cancer has been minimally studied and the results are controversial. For the above, the objective of this work was to determine the hormonal regulation exerted by natural ovarian steroids on proliferation and apoptosis in an experimental model of colon cancer in ovariectomized rats treated with 17-beta estradiol and progesterone. Sprague–Dawley rats were exposed to the carcinogen 1,2-dimethylhydrazine to induce colon tumors. Thirty days later, the rats were ovariectomized and treated with estradiol (60 μg/kg), progesterone (10 mg/kg), estradiol plus progesterone (60 μg/kg and 10 mg/kg) or vehicle. We observed no significant differences in colon cancer incidence and tumor multiplicity between the groups. Nevertheless, we observed a decrease in PCNA expression and a greater number of apoptotic index, higher expression of caspase 3, cleaved PARP and cleaved caspase 8 in tumors, confirming the activation of the extrinsic pathway of apoptosis by the combined treatment. In addition, we observed a higher expression of estrogen receptor beta in these tumors. We conclude that the action of both hormones, estradiol and progesterone, is necessary to reduce proliferation and increase apoptosis in colon tumors, probably through estrogen receptor beta activation.

Sexual Dimorphism in Colon Cancer

“…Moreover, the number of postmenopausal women using natural progesterone instead of synthetic progestins in hormone replacement therapy is increasing. There is some recent evidence implicating progesterone in reducing CRC but this seems to be additive to estrogen signaling via the estrogen receptor ERβ ( 45 ). A retrospective clinical trial found no evidence for association of progesterone receptor (PGR) expression with CRC survival outcomes ( 46 ).…”

Estrogen and Progesterone Expression in Colorectal Carcinoma: A Clinicopathological Study

“…Also, Elevated ER beta expression was associated with a better prognosis in patients with CRC as shown in recent studies (Stevanato Filho et al, 2018, Topi et al, 2017. Also, the presence of both ER and progesterone (PR) expression was associated with lower proliferation and more apoptosis of colon cancer, probably through ER receptor beta activation (Sasso et al, 2019).…”

“…Slides were assessed by reviewing them at 40x and 100x magnification to assess the distribution and intensity of the stain and at 200x and 400x magnification to semi-quantitatively evaluate the scoring parameters of the immunostaining. The immunoreactive score (IRS) was determined by multiplying an estimate of the percentage of the immunoreactive cells with an estimate of the staining intensity as by Sasso (2019). Staining quantity is scored as follows: No staining= 0, <10% of cells stained= 1, 11-33% of cells stained = 2, 34-65% of cells stained = 3 and >65% of cells stained= 4.…”

Synbiotic Combination of Djulis (Chenopodium formosanum) and Lactobacillus acidophilus Inhibits Colon Carcinogenesis in Rats

“…Besides, the number of SIM-ACF was positively correlated to PCNA expression (r = 0.55, p < 0.05). A previous study found that both inhibition of PCNA expression and promotion of caspase-3 expression were confirmed in the activation of the extrinsic pathway of apoptosis [49]. Increasing the Bax/Bcl-2 ratio or inhibiting Bcl-2 expression, both markers of apoptosis, by treatment with bioactive compounds in colon cancer cells limited their growth [50,51].…”