NUTRITIONAL HERBS AS TESTABLE THERAPEUTIC ALTERNATIVES FOR POST-MENOPAUSAL COLON CANCER
Main Article Content
Abstract
Background: Chemotherapeutic options for management of post-menopausal colon cancer are associated with systemic toxicity, therapy resistance and survival of cancer stem cells. These aspects promote progression of metastatic disease. In post-menopausal colon cancer estrogens are hypothesized to play a protective role, and phytoestrogenic nutritional herbs may provide valuable mechanistic leads for growth inhibition of cancer. Investigations using cellular models relevant to this cancer subtype provide mechanistic evidence for carcinogenesis, role of estrogens in post-menopausal colon cancer and identify susceptible molecular targets.
Objectives: This mini-review provides a systematic discussion of published evidence on i) experimental systems developed from colon carcinoma and colonic epithelium that facilitate identification of mechanistic link between Wnt/β-catenin signaling and estrogen receptor signaling, ii) inhibitory efficacy of natural products such as dietary phytochemicals and Chinese nutritional herbs and iii) Conceptual and technical limitations that define rationale for future research.
Conclusions: Molecular characterization and mechanistic leads have validated the experimental systems to investigate growth inhibitory efficacy of natural products. Major limitations provide rationale for future research that facilitate clinical relevance and translatability of the data.
Keywords:
Colon cancer, Wnt/β-catenin pathway, Estrogen receptor-β, nutritional herbs
Article Details
How to Cite
TELANG, Nitin T..
NUTRITIONAL HERBS AS TESTABLE THERAPEUTIC ALTERNATIVES FOR POST-MENOPAUSAL COLON CANCER.
Medical Research Archives, [S.l.], v. 14, n. 1, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7101>. Date accessed: 03 feb. 2026.
doi: https://doi.org/10.18103/mra.v14i1.7101.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. American Cancer Society Facts and Figures 2025. American Cancer Society. Atlanta, GA.
2. Campbell-Thompson M, Lynch IJ, Bharadwaj B: Expression of estrogen receptor (ER) subtypes and ER-β isoforms in colon cancer. Cancer Res. 2001, 61: 632-640. PMID: 11212261.
3. Ditonno I, Losurdo G, Rendina M, Pricci M, Girardi B, Lerardi E, Di Leo A. Estrogen receptors in colorectal cancer: Facts, Novelties and perspectives. Curr. Oncol. 2021, 28: 4256-4263. DOI: 10.3390/curonc ol28060361. .
4. Filho PRS, Junior SA, Begnami MD, et al: Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer. BMC Cancer 17: 754. DOI: 10.1186/s12885-017-3688-4.
5. Filho PRS, Junior SA, Begnami MD, et al: Estrogen receptor β as a prognostic marker of tumor progression in colorectal cancer with familial adenomatous polyposis and sporadic polyps. Pathol. Oncol. Res. 2018, 24: 533-540. DOI: 10.1007/s1225 3-017-0268-5.
6. DitonnoI, Novielli D, Celiberto F, et al: Molecular pathways of carcinogenesis in familial adenomatous polyposis. Int. J. Mol. Sci. 2023, 24: 5687. DOI: 10.33 90/ijms24065687.
7. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990, 61: 759-76 DOI: 10.1016/0092—8674(90)90186-i.
8. Fodde r, Smits R, Clevers H: APC, signal transduction and genetic instability in colon cancer. Nat. Rev. Cancer 2001, 1: 55-67. DOI: 10.1038/3509 4067.l
9. Anastas JN, Moon RT: Wnt signaling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 2013, 13: 11-26. DOI: 10.1038/nrc3419.
10. Bian J, Dannappel M, Wan C, et al: Transcriptional regulation of Wnt/β-catenin pathway in colorectal cancer. Cells 2020, 9: 2125. DOI: 10.3390/cells9092125.
11. Shi G, Li Y, Shen H, et al: Intestinal stem cells in in intestinal homeostasis and colorectal tumorigenesis. Life Med. 2024, 3: Inae042. DOI:10.1093/lifemedi/I nae042.
12. Cho NL, Javid SH, Carothers AM, et al: Estrogen receptors alpha and beta are inhibitory modifiers of Apc-dependent tumorigenesis in the proximal colon of Min/+ mice. Cancer Res. 2007, 67: 2366-2372. DOI: 10.1158/0008-5472.CAN-06-3026. et al 2007
13. National Comprehensive Cancer network. Clinical practice guidelines in oncology: Colon cancer. 2025. www.http://nccn.org.
14. Beazer-Barkley Y, Levy DB, Moser AR, et al: Sulindac suppresses tumorigenesis in the min mouse. Carcinogenesis1996, 17: 1757-1760. DOI: 10.1093/carcin/17.8.1757.
15. Boolbol SK, Dannenberg AJ, Chadburn A, et al: Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res. 1996, 56: 2556-2560. PMID: 8653697.
16. Jacoby RF, Seibert K, Cole CE, et al: The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res. 60: 5040-5044. PMID: 11016626.
17. Giardiello FM, Hamilton SR, Krush AL, et al: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N. Engl. J. Med. 1993, 328: 1313-1316. DOI: 10.1056/NEJM1 99305063281805.
18. Steinbach G, Jynch PM, Phillips RK, et al: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Med. 2000, 342: 1946-1952. DOI: 10.1056/NEJM20000 6293422603.
19. Hong M, Tan HY, LiS, et al: Cancer stem cells: the potential targets of Chinese medicines and their active compounds. Int. J. Mol. Sci. 2016, 17: 893.
20. Aiello P, Sharghi M, Mansourkhani SM, et al: Medicinal plants in the prevention and treatment of colon cancer. Oxidat. Med. Cell Longev. 2019, 2019, 2075614. DOI: 10.1155/2019/2075614.
21. Manogaran P, Umapathy D, Karthikeyan M, et al: Dietary phytochemicals as a potential source for targeting cancer stem cells. Cancer Investig. 2021, 39: 349-368. DOI: 10.1080/07357907.2021.1894569.
22. Naujokat C, Mc Kee DL: The big five phytochemicals targeting cancer stem cells: Curcumin, EGCG, sulforaphane, resveratrol and genisteinCur. Med. Chem. 2021, 28: 4321-4342. DOI: 10.2174/09 298673276662002281 10738.
23. Kuiper GG, Lemmen JG, Carisson B, et al: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998, 139: 4252-4263, DOI: 10.121 0/endo.139.10.6216.
24. Lai T-Y, Chen L-M, Lin J-Y et al: 17beta-estradiol inhibits prostaglandin E2-induced COX-2 expression and cell migration by suppressing Akt and ERK1/2 signaling pathways in human LoVo colon cancer cells. Mol Cell Biochem. 2010, 342: 63-70. DOI: 10.1007/11010-010-0469-7.
25. Martineti V, Picariello L, Tognarini I, et al: ER beta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. Endocr. Relat. Cancer 2005, 12: 455-469. DOI:10.1677/erc.1.00861.
26. Hartman J, Edvardsson K, Lindberg K, et al: Tumor repressive functions of estrogen receptor beta in SW480 colon cancer cells. Cancer res. 2009, 69: 6100-6106. DOI: 10.1158/0008-5472.CAN-09-0506.
27. Su LK, Kinzler KW, Vogelstein B, et al: Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 1992, 256 (5057): 668-670. DOI: 10.1126/science.1350108.
28. Fodde R, Edelmann W, Yang K, et al: A targeted chain termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc. Natl. Acad. Sci. USA 1994, 91: 8969-8973. DOI: 10.1073/pnas.9 1.91.8969.
29. Telang N, Katdare M: Novel cell culture model for prevention of carcinogenic risk in familial adenomatous polyposis syndrome. Oncol. Rep. 2009, 21: 1017-1021. DOI: 10.3892/or_00000318.
30. Telang N: Anti-inflammatory drug resistance selects putative cancer stem cells in a cellular model for genetically predisposed colon cancer. Oncol. Letts. 2018, 15: 542-648. DOI: 10.3892/ol.2017.7147.
31. Telang N: Drug resistant stem cells: Novel approach for colon cancer therapy. Int. J. Mol. Sci. 2022, 23: 2519. DOI: 10.3390/ijms23052519.
32. Edelmann W, Yang K, Karaguchi M, et al: Tumorigenesis in Mlh1/1638N mutant mice. Cancer Res. 1999, 59: 1301-1307. PMID: 10096563.
33. Telang N: Isolation and characterization of chemo-resistant stem cells from a mouse model for hereditary non-polyposis colon cancer. Stem Cells and Cloning: Advances and Applications. 2021, 14: 19-25. DOI: 10.2147/SCCAA.S312929.
34. Fiorelli G, Picanello L, Martineti V, et al: Functional estrogen receptor beta in colon cancer cells. Biochem. Biophys. Res. Commun. 1999, 261: 521-527. DOI: 10.1006/bbrc.1999.1062.
2. Campbell-Thompson M, Lynch IJ, Bharadwaj B: Expression of estrogen receptor (ER) subtypes and ER-β isoforms in colon cancer. Cancer Res. 2001, 61: 632-640. PMID: 11212261.
3. Ditonno I, Losurdo G, Rendina M, Pricci M, Girardi B, Lerardi E, Di Leo A. Estrogen receptors in colorectal cancer: Facts, Novelties and perspectives. Curr. Oncol. 2021, 28: 4256-4263. DOI: 10.3390/curonc ol28060361. .
4. Filho PRS, Junior SA, Begnami MD, et al: Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer. BMC Cancer 17: 754. DOI: 10.1186/s12885-017-3688-4.
5. Filho PRS, Junior SA, Begnami MD, et al: Estrogen receptor β as a prognostic marker of tumor progression in colorectal cancer with familial adenomatous polyposis and sporadic polyps. Pathol. Oncol. Res. 2018, 24: 533-540. DOI: 10.1007/s1225 3-017-0268-5.
6. DitonnoI, Novielli D, Celiberto F, et al: Molecular pathways of carcinogenesis in familial adenomatous polyposis. Int. J. Mol. Sci. 2023, 24: 5687. DOI: 10.33 90/ijms24065687.
7. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990, 61: 759-76 DOI: 10.1016/0092—8674(90)90186-i.
8. Fodde r, Smits R, Clevers H: APC, signal transduction and genetic instability in colon cancer. Nat. Rev. Cancer 2001, 1: 55-67. DOI: 10.1038/3509 4067.l
9. Anastas JN, Moon RT: Wnt signaling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 2013, 13: 11-26. DOI: 10.1038/nrc3419.
10. Bian J, Dannappel M, Wan C, et al: Transcriptional regulation of Wnt/β-catenin pathway in colorectal cancer. Cells 2020, 9: 2125. DOI: 10.3390/cells9092125.
11. Shi G, Li Y, Shen H, et al: Intestinal stem cells in in intestinal homeostasis and colorectal tumorigenesis. Life Med. 2024, 3: Inae042. DOI:10.1093/lifemedi/I nae042.
12. Cho NL, Javid SH, Carothers AM, et al: Estrogen receptors alpha and beta are inhibitory modifiers of Apc-dependent tumorigenesis in the proximal colon of Min/+ mice. Cancer Res. 2007, 67: 2366-2372. DOI: 10.1158/0008-5472.CAN-06-3026. et al 2007
13. National Comprehensive Cancer network. Clinical practice guidelines in oncology: Colon cancer. 2025. www.http://nccn.org.
14. Beazer-Barkley Y, Levy DB, Moser AR, et al: Sulindac suppresses tumorigenesis in the min mouse. Carcinogenesis1996, 17: 1757-1760. DOI: 10.1093/carcin/17.8.1757.
15. Boolbol SK, Dannenberg AJ, Chadburn A, et al: Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res. 1996, 56: 2556-2560. PMID: 8653697.
16. Jacoby RF, Seibert K, Cole CE, et al: The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res. 60: 5040-5044. PMID: 11016626.
17. Giardiello FM, Hamilton SR, Krush AL, et al: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N. Engl. J. Med. 1993, 328: 1313-1316. DOI: 10.1056/NEJM1 99305063281805.
18. Steinbach G, Jynch PM, Phillips RK, et al: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Med. 2000, 342: 1946-1952. DOI: 10.1056/NEJM20000 6293422603.
19. Hong M, Tan HY, LiS, et al: Cancer stem cells: the potential targets of Chinese medicines and their active compounds. Int. J. Mol. Sci. 2016, 17: 893.
20. Aiello P, Sharghi M, Mansourkhani SM, et al: Medicinal plants in the prevention and treatment of colon cancer. Oxidat. Med. Cell Longev. 2019, 2019, 2075614. DOI: 10.1155/2019/2075614.
21. Manogaran P, Umapathy D, Karthikeyan M, et al: Dietary phytochemicals as a potential source for targeting cancer stem cells. Cancer Investig. 2021, 39: 349-368. DOI: 10.1080/07357907.2021.1894569.
22. Naujokat C, Mc Kee DL: The big five phytochemicals targeting cancer stem cells: Curcumin, EGCG, sulforaphane, resveratrol and genisteinCur. Med. Chem. 2021, 28: 4321-4342. DOI: 10.2174/09 298673276662002281 10738.
23. Kuiper GG, Lemmen JG, Carisson B, et al: Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998, 139: 4252-4263, DOI: 10.121 0/endo.139.10.6216.
24. Lai T-Y, Chen L-M, Lin J-Y et al: 17beta-estradiol inhibits prostaglandin E2-induced COX-2 expression and cell migration by suppressing Akt and ERK1/2 signaling pathways in human LoVo colon cancer cells. Mol Cell Biochem. 2010, 342: 63-70. DOI: 10.1007/11010-010-0469-7.
25. Martineti V, Picariello L, Tognarini I, et al: ER beta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. Endocr. Relat. Cancer 2005, 12: 455-469. DOI:10.1677/erc.1.00861.
26. Hartman J, Edvardsson K, Lindberg K, et al: Tumor repressive functions of estrogen receptor beta in SW480 colon cancer cells. Cancer res. 2009, 69: 6100-6106. DOI: 10.1158/0008-5472.CAN-09-0506.
27. Su LK, Kinzler KW, Vogelstein B, et al: Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 1992, 256 (5057): 668-670. DOI: 10.1126/science.1350108.
28. Fodde R, Edelmann W, Yang K, et al: A targeted chain termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc. Natl. Acad. Sci. USA 1994, 91: 8969-8973. DOI: 10.1073/pnas.9 1.91.8969.
29. Telang N, Katdare M: Novel cell culture model for prevention of carcinogenic risk in familial adenomatous polyposis syndrome. Oncol. Rep. 2009, 21: 1017-1021. DOI: 10.3892/or_00000318.
30. Telang N: Anti-inflammatory drug resistance selects putative cancer stem cells in a cellular model for genetically predisposed colon cancer. Oncol. Letts. 2018, 15: 542-648. DOI: 10.3892/ol.2017.7147.
31. Telang N: Drug resistant stem cells: Novel approach for colon cancer therapy. Int. J. Mol. Sci. 2022, 23: 2519. DOI: 10.3390/ijms23052519.
32. Edelmann W, Yang K, Karaguchi M, et al: Tumorigenesis in Mlh1/1638N mutant mice. Cancer Res. 1999, 59: 1301-1307. PMID: 10096563.
33. Telang N: Isolation and characterization of chemo-resistant stem cells from a mouse model for hereditary non-polyposis colon cancer. Stem Cells and Cloning: Advances and Applications. 2021, 14: 19-25. DOI: 10.2147/SCCAA.S312929.
34. Fiorelli G, Picanello L, Martineti V, et al: Functional estrogen receptor beta in colon cancer cells. Biochem. Biophys. Res. Commun. 1999, 261: 521-527. DOI: 10.1006/bbrc.1999.1062.