Visible inhibition of lung cancer in mice given Hesperidin (orally, in moderate human dose)

cs3000

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Hesperidin Inhibits Lung Cancer In Vitro and In Vivo Through PinX1

nice in vivo study on cancer. hesperidins effect on lung cancer at 100mg / kg mice dose fed orally , for 25 days.
inhibition after in vast majority.
8mg/kg human dose

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Based on the in vitro anti-tumor effect of hesperidin, we think hesperidin may be a potent compound for treating lung cancer
tumor growth was significantly inhibited after hesperidin administration (Figure 5A). During the experiment, none of the mortality and macroscopic metastases were found upon gross visual examination of the livers, lungs, hearts, and kidneys of the tumor-bearing mice treated with or without hesperidin. When the experiment was complete, tumor weight and tumor volume were recorded as shown in Figure 5, where it was shown that hesperidin significantly reduced tumor volume (Figure 5B) and tumor weight (Figure 5C). The results suggested that hesperidin can effectively inhibit tumor growth in vivo

edit: doesnt show tumor shrinkage, but it shows greatly slowed tumor growth with 50% less tumor weight by 25 days.
aka 2x faster cancer growth in the non-hesperidin group

with great safety profile
*as long as you are aware of the p450 enzyme inhibition by this affecting certain medications

Hesperidin Shows No Toxicity While Anti-Tumor​

In the in vivo study, we chose a relatively high dose (100 mg/kg) of hesperidin in this investigation based on a previous study (Muhammad et al., 2019). The general state of mice, body weight, and food intake were recorded. As shown in Figures 6A,B, compared to the tumor-bearing group, body weight and food intake did not differ from the mice in the hesperidin-treated group. Furthermore, after the experiment was completed, the mice were dissected, and there was no visible pathological damage in all tissues and organs. Livers and kidneys from the mice treated with or without hesperidin were employed to measure the potential toxicity of hesperidin by H and E staining, which also showed no abnormal changes (Figure 6C). The aforementioned results also indicated that hesperidin is safe at the dose of 100 mg/kg.

(which is 500mg - 700mg human dose)
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no significant negative side effects on liver or kidneys or all organs & tissues. food intake did not reach significant difference but low doses have been shown to restore some appetite lost by cancer treatments, which is another boost where appetite can be suppressed.


probably has a similar effect for many cancers.
hesperidin significantly increased the pinX1 protein expression in a concentration-dependent manner. The aforementioned results indicated that hesperidin is a potential anti-tumor candidate with less lethality on normal lung cells.
Interestingly, the pinX1 protein expression in lung cancer patients is positively related to overall survival time, which is in accordance with a study on thyroid cancer.
same applies to humans "Previous studies have suggested that PinX1 is an intrinsic telomerase inhibitor and a putative tumour-suppressor gene in human cancers"
and shown in some other types too
favourable marker in cervical cancer also PINX1 protein expression summary - The Human Protein Atlas
and breast cancer and ovarian cancer
https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-015-0332-2
Both the 5-year OS and 5-year DFS in patients with colorectal cancer are lower in patients with low/negative expression of PinX1 protein compared with that in patients with high/moderate expression of PinX1
In brief, our study shows that hesperidin can inhibit LLC cell proliferation, migration, and invasion and induce senescence via pinX1.

and a great thing about it is medical corporations cant lock it behind a healthcare wall as a natural flavanoid. readily accessible to many people


in a cell study hesperidin created cancer cell destruction too Hesperidin exhibits in vitro and in vivo antitumor effects in human osteosarcoma MG‑63 cells and xenograft mice models via inhibition of cell migration and invasion, cell cycle arrest and induction of mitochondrial‑mediated apoptosis Retraction in /10.3892/ol.2023.13703
(but this study was retracted for some reason)
The fact that hesperidin triggers apoptosis was also confirmed by western blotting. The results of SEM revealed that hesperidin triggers apoptosis in cancer MG-63cells in a concentration-dependent manner and apoptotic cells increased with an increase in the concentration of hesperidin
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In brief, the present study revealed that hesperidin shows in vitro and in vivo antitumor and apoptotic effects in MG-63 human osteosarcoma cells via the mediation of cell cycle arrest, inhibition of cell migration and invasion and mitochondrial mediated apoptosis.


500mg is probably found in 1L of orange juice. but varies (and not sure if other compounds in it could interfere leading to slightly lower equivalent dose. one study showed similar hesperidin blood rise with OJ estimated equivalent dose compared to solo hesperidin). and obviously the dosing isnt the same unless you drank all the orange at one sitting.


I wonder if doubling the dose to 1g-1.5g would stop growth completely ? or close
a rat study showed increasingly beneficial effects for correcting diabetes up to 80mg/kg. for mice dose that would be 160mg/kg -

making me think there might be more effect to be gained here too by increasing the 100mg/kg dose used +60% up to 13mg/kg human dose instead of 8mg/kg
for the potential full anti-cancer effect
 

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cs3000

cs3000

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https://www.thieme-connect.com/products/ejournals/pdf/10.4103/ijmbs.ijmbs_21_18.pdf
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In this study, a xenograft model of lung and liver metastasis was used to test the ability of Hsp to decrease the metastatic ability of laryngeal cancer using Hep2 cell line, In the current study, Hsp significantly decreased and inhibited metastasis in a dose‑dependent manner of Hep2 laryngeal cancer cells with no detected toxicity.
To the best of our knowledge, it has never been reported that Hsp decreases the ability of laryngeal cancer cells to metastasize to the liver and lung.

The current findings proved that low concentrations of Hsp significantly reduced metastasis and higher levels almost abolished metastasis

perhaps via suppression of Ang1 expression and secretion in tumor cells​

The current results showed that low concentrations of Hsp (10 and 20 μM) induced apoptosis of laryngeal cancer cells efficiently in a dose‑dependent manner. A higher Hsp concentration markedly increased apoptosis. Previous studies showed that Hsp at a high concentration (160 μM) induced apoptotic signaling including upregulation of Bax, cleavages of caspase‑3 and down‑regulation of Bcl‑xl in mesothelioma cells

Furthermore, Hsp inhibits glycogen synthase kinase‑3 beta signaling cascades and induces apoptosis in experimental colon carcinogenesis
The anticancer properties of hesperidin result from the C4’=C8’ double bonds of the A and B rings, C5=C6, respectively, the 4‑carbonyl group of the C ring and 3’’–o‑hydroxy, 4’’‑o‑methoxy system in the B ring. Hsp serves as a hydrogen donor for α‑tocopherol radical, thus regenerating α‑tocopherol, scavenges superoxide radical (LOO), singlet oxygen (1O2 ), hydroxyl radical (OH), nitrogen oxide (NO), superoxide anion radical (O2 ‑) and hesperidin radical is formed.[20,21] It is also proposed that the higher antioxidant activity is related to the greater number of hydroxyl groups on its flavonoid nucleus

Several structural features were shown to be important for the effect of flavonoids on glutamate‑mediated apoptosis including the presence of a hydroxyl group on C–3’’ and a 4’‑8’ double bond in conjugation with a C–4 ketone function. The formation of hydrogen bonds between the ketonic oxygen and the hydroxyls at C–3’’ and C–5 may have some influence on the scavenging power

40mg/kg rat dose was highest dose. & was a dose dependent effect - so 80mg/kg rat dose maybe could have completed abolished all metastasis



Naringenin also has good effect here. worked better than hesperetin. (this study isnt as controlled, e.g dose was put into food so the 2 groups could have had different dose intakes, and theres some typos e.g 18 days in summary vs 16 days in article) . but not sure about compared to hesperidin. & not sure on overall effects

Control group survival: 16 or 18 days
Naringenin group survival: 38 days
Hesperetin group survival: 27 days

https://www.researchgate.net/public...reduction_of_the_in_vivo_metastatic_potential
The in vitro and in vivo effects of two flavonons, naringenin (NG) and hesperitin (HP) on the proliferation rate of highly metastatic murine B16-F10 melanoma cell were investigated. NG or HP treatment of melanoma cells produced a remarkable reduction of cell proliferation, paralleled with both the lowering of the intracellular levels of polyamine, spermidine and spermine and the enhancement of transglutaminase (TGase, EC 2.3.2.13) activity.
Orally administered NG or HP in C57BL6/N mice inoculated with B16-F10 cells affected the pulmonary invasion of melanoma cells in an in vivo metastatic assay. The number of lung metastases detected by a computerized image analyzer was reduced, compared to untreated animals, by about 69% in NG-treated mice and by about 36% in HP-treated mice. Survival studies showed that 50% of the NG-treated animals died 38 ± 3.1 days after tumor cell injection (control group: 18 ± 1.5 days) and HP-treated mice died 27 ± 2.3 days after cell inoculation. Taken together, these findings provide further evidences for the potential anticancer properties of dietary flavonoids as chemopreventive agents against malignant melanoma.
 
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