Oranges (Citrus sinensis), also known as sweet oranges, contain compounds with antioxidant, antiproliferative, radioprotective, neuroprotective and chemopreventive properties. Oranges and closely-related fruits incorporate beta-carotene, beta-cryptoxanthin, ferulic acid, fiber, hesperetin and hesperidin, limonene, naringenin and naringin, nobiletin, tangeretin, vitamin C and zeaxanthin.
Orange juice has been shown to reduce the extent of DNA damage caused by certain mutagens. Orange extracts and orange compounds have also been shown to inhibit the growth of bladder, cervix, colon, liver, lung, pancreas and stomach cancer cells, as well as leukemia and lymphoma cells. However, several studies have reported that people with diets high in citrus fruits appear to be at increased risk of malignant melanoma, possibly from ingesting psoralens, a type of photosensitizing compound found in citrus.

Breast cancer-related effects of eating oranges

Although research concerning the chemopreventive properties of oranges is promising, it has for the most part been conducted using cell studies and animal models of breast cancer. However, Korean and Uruguayan studies have found an association between orange juice consumption and lower incidence of breast cancer. In addition, one large U.S. prospective study reported that women with high orange intake in early adulthood experienced reduced risk of breast cancer in middle age and later years.
Oranges, tangerines, clementines and their peels are sources of the flavonoids hesperetin and its glycoside hesperidin, naringenin and its glycoside naringin, tangeretin, nobiletin and limonene, as well as several carotenoids (beta-carotene, beta-cryptoxanthin and zeaxanthin), ferulic acid, and vitamin C, all of which have been shown to have chemopreventive properties (capable of preventing or slowing cancer development) with respect to breast cancer.
On the other hand, some of the chemopreventive compounds found in oranges or their components can interfere with the treatment effects of tamoxifen and some other systemic therapies. Were it not for this fact, oranges would be on our Recommended food list. Orange peel and related foods and products, as well as commercial orange juice, should be avoided during aromatase inhibitor, cyclophosphamide (Cytoxan), tamoxifen (Nolvadex), and Taxol (paclitaxel) treatment. The micronutrient sections below include explanations of this advice.

Hesperetin and hesperidin

Hesperetin is the parent flavanone of hesperidin. Hesperidin is found most abundantly in the peel, pith and membranous parts of sweet oranges, sour oranges such as Seville oranges, tangerines, kumquats, and other citrus fruits. Food and related sources of hesperidin include orange tea, orange marmalade, orange zest, orange peel extract, orange peel oil, and dishes such as Szechuan Orange Chicken that incorporate dried orange peel. Orange juice made by hand from sweet oranges without a great deal of pressure on the peels does not contain significant levels of hesperidin. The higher pressures used to to make commercial orange juice can greatly increase the fraction of hesperidin.
Hesperidin has been shown to reduce triple negative breast cancer (ER-/PR-/HER2-) and ER+/PR+ cell viability in a dose- and time-dependent manner and to inhibit ER+/PR+ cell proliferation, colony formation, and migration. Hesperetin has been shown to inhibit aromatization (the process by which androgens are converted into estrogens in the body) in a mouse model of ER+ breast cancer. Hesperetin has also been reported to act as an HER2 inhibitor, with antiproliferative, pro-apoptotic and other anti-cancerous activities against HER2+ breast cancer cells.
Pre-treatment with hesperidin before Adriamycin (doxorubicin) chemotherapy has been demonstrated to reduce tumor numbers and increase survival in a rat model of breast cancer. The same 2021 study also found that hesperidin helped protect against Adriamycin-induced toxicity in the vital organs of the animals, apparently by reducing inflammation.
Hesperidin can interfere with some breast cancer treatments
Hesperidin has the potential to interfere with chemotherapy regimens containing cyclophosphamide, which is an alkylating agent frequently used in combination with anthracyclines (Adriamycin, epirubicin) and/or taxanes (Taxol, Taxotere). Examples of such regimens include TAC (Taxotere, Adriamycin and cyclophosphamide), TEC (Taxotere, epirubicin, and cyclophosphamide) and FEC (5-fluorouracil, epirubicin and cyclophosphamide) chemotherapy.
While, as noted above, hesperidin has been shown to inhibit aromatase activity, paradoxically, it also has the potential to interfere with aromatase inhibitor treatment. Orange peel and related products, as well as commercial orange juice should be avoided during chemotherapy that includes cyclophosphamide, as well as during aromatase inhibitor treatment.

Naringenin and naringin

Naringenin is the parent flavanone of naringin. While grapefruit is the most abundant source of naringenin, it is also found in oranges. Naringenin has been shown to inhibit metastasis in a mouse model of breast cancer. Naringenin also has cytotoxic activity against both ER+/PR+ and triple negative breast cancer cells.
Naringenin has been found to inhibit the proliferation of ER+/PR+ breast cancer cells by impairing glucose uptake. In addition, naringenin has been shown to inhibit ER+ breast cancer cell growth and migration in the presence of estradiol (E2). Like hesperetin, naringenin has also been shown to act as an HER2 inhibitor, with antiproliferative, pro-apoptotic and other anti-cancerous activities against HER2+ breast cancer cells.
One study reported that combining the chemotherapy drug Adriamycin with naringenin and the anti-diabetes drug metformin resulted in lower tumor volume and weight compared to treatment with Adriamycin alone in a mouse model of triple negative breast cancer.

Tangeretin

Tangeretin is a flavonoid found in citrus peel, including that of tangerines and other types of mandarin oranges, as well as oranges and related fruits. Tangeretin has been shown to inhibit the growth and invasive properties of various types of breast cancer cells. A 2020 study reported that treatment with tangeretin reducing tumor and angiogenesis markers in a rat model of carcinogen-induced breast cancer. Another 2020 study found that tangeretin inhibited breast cancer cell proliferation, breast cancer stem cell formation, and tumor growth. Tangeretin has also been shown to increase the anti-breast cancer activity of the diabetes drug metformin in several breast cancer cell lines.
Tangeretin can interfere with tamoxifen treatment
Tangeretin has been shown to reduce the beneficial effects of tamoxifen treatment. In one study using a mouse model of breast cancer, the survival time of tumor-bearing mice treated with tamoxifen plus tangeretin (administered in their drinking water) was shorter than that of similar mice treated with tamoxifen alone. In fact, adding tangeretin to mouse drinking water failed to inhibit tumor growth, and adding it to drinking water together with tamoxifen completely extinguished tamoxifen's anti-tumor effects. However, no evidence was found that tangeretin alone had a tumor-promoting effect. Tangeretin supplements, orange peel and related products, and commercial orange juice should not be used during treatment with tamoxifen. Orange juice made by hand without a great deal of pressure on the orange peels is acceptable.

Nobiletin

Nobiletin is a flavone which, like tangeretin, is found in the peels of tangerines and other types of mandarin oranges, as well as oranges and related fruits. Nobiletin has been reported to have cytotoxic activities against ER+/PR+/HER2-, as well as ER+/PR+/HER2+ and ER-/PR-/HER2+ breast cancer cells, without harming normal breast cells. Nobiletin has also been shown to increase the cytotoxic activity of Adriamycin in ER+/PR+ cells. However, normal breast cells are not affected by nobiletin treatment.
Nobiletin has also been found to inhibit triple negative breast cancer cell growth and reduce their cancer stem cell populations in tumor patients. Nobiletin also increases the treatment effects of Adriamycin in triple negative breast cancer cells and this synergistic activity is considerably stronger than in ER+/PR+ cells.

Limonene

Limonene, a cyclic monoterpene, and its D isomer D-limonene, are found primarily in orange and other citrus peels. Limonene has been reported to have chemopreventive effects with respect to breast cancer, but the evidence is limited compared to that of other citrus micronutrients. One 2021 study reported that limonene could interfere with the effectiveness of Taxol.

Orange carotenoids

Oranges, tangerines and closely related fruits are a good source of the carotenoids beta-carotene, beta-cryptoxanthin and zeaxanthin. Dietary carotenoids have been shown to inhibit estrogen signaling of both estradiol and the soy isoflavone genistein, thereby reducing their harmful effects in ER+ breast cancer. Beta-carotene has also been shown to inhibit multidrug resistance in cancer cells. Relatively higher serum levels of carotenoids in breast cancer survivors have both been found to be associated with greater likelihood of breast cancer-free survival.

Ferulic acid

Oranges incorporate the plant phenolic ferulic acid, which has substantial anticancer activity. Ferulic acid has been shown to reduce proliferation and increase programmed cell death in ER+/PR+ and triple negative breast cancer cells. It also has been shown to reduce metastasis in an animal model of triple negative breast cancer. In addition, ferulic acid has been demonstrated to synergistically enhance the treatment effects of Taxol and epirubicin chemotherapy. One study reported that ferulic acid reduced the heart damage (cardiomyopathy) caused by Adriamycin in an animal model of cancer treatment.

Vitamin C

High intakes of fruits and vegetables rich in vitamin C have been found to be associated with lower breast cancer risk. Vitamin C appears to act synergistically with other nutrients in the diet to oppose cancer. Vitamin C has been found to be cytotoxic against ER+/PR+ and triple negative breast cancer cells.

Additional comments

Non-organic oranges should be washed thoroughly before using to prevent a transfer of pesticides and other contaminants to the flesh during cutting.

Sources of information provided in this webpage

The information above, which is updated continually as new research becomes available, has been developed based solely on the results of academic studies. Clicking on any of the underlined terms will take you to its tag or webpage, which contain more extensive information.
Below are links to 20 recent studies concerning this food and its components. For a more complete list, including less recent studies, please click on oranges.