How Supplements and Repurposed Drugs May Impact Tumor Cells: Exploring the Science Behind Emerging Regimens

While conventional therapies like chemotherapy and immunotherapy remain cornerstones of cancer care, a growing number of patients and researchers are exploring how non-toxic supplements and repurposed drugs might contribute to cancer control — especially in the context of metabolic and microenvironmental vulnerabilities of tumors. In this post, we break down the putative mechanisms and supporting evidence behind a regimen that includes vitamin D, curcumin, metformin, aspirin, and other agents — and we expand it to include mebendazole and ivermectin, two antiparasitic drugs gaining traction for their anticancer effects. 🔬 The Regimen: Overview This post includes: Supplements: Vitamin D, curcumin, taurine, fisetin, melatonin, flaxseed, pomegranate extract Repurposed drugs: Metformin, aspirin, mebendazole, ivermectin These agents may impact cancer biology through: Inhibiting cell proliferation Inducing apoptosis Modulating the tumor microenvironment Inhibiting angiogenesis Supporting immune surveillance 🧠 How Each Agent May Affect Tumor Cells 1. Vitamin D Mechanism: Binds the vitamin D receptor (VDR), inducing cell cycle arrest and apoptosis while reducing angiogenesis. Cancer relevance: Deficiency correlates with worse outcomes in several cancers[^1]. 2. Curcumin Mechanism: Inhibits NF-κB, COX-2, and STAT3; modulates epigenetics; sensitizes cells to chemotherapy. Cancer relevance: Active against prostate, breast, colon, and pancreatic cancer in preclinical studies[^2]. 3. Taurine Mechanism: Antioxidant and mitochondrial stabilizer; may promote cell differentiation and inhibit calcium-mediated signaling. Cancer relevance: Some animal models show suppression of hepatocellular and colon cancer[^3]. 4. Fisetin Mechanism: Flavonoid that induces apoptosis, inhibits PI3K/Akt, and acts as a senolytic (removing aging, pro-inflammatory cells). Cancer relevance: Suppresses growth in prostate, colon, and lung cancer models[^4]. 5. Melatonin Mechanism: Enhances apoptosis, reduces angiogenesis, modulates circadian regulation, and protects normal cells during chemo/radiotherapy. Cancer relevance: Meta-analysis supports survival benefit when used adjunctively[^5]. 6. Metformin Mechanism: Activates AMPK, inhibits mTOR, reduces insulin/IGF-1 signaling — all critical for tumor metabolism. Cancer relevance: Associated with improved survival in breast, colorectal, and prostate cancer, especially among diabetics[^6]. 7. Aspirin Mechanism: Inhibits COX-1/2, reducing prostaglandin-mediated inflammation and platelet-tumor interactions. Cancer relevance: Daily low-dose aspirin is associated with reduced colorectal cancer incidence and may inhibit metastasis[^7]. 8. Pomegranate Extract Mechanism: Rich in ellagitannins, inhibits aromatase, suppresses NF-κB, and slows PSA progression. Cancer relevance: Early trials show slower PSA doubling time in prostate cancer[^8]. 9. Flaxseed Mechanism: Contains lignans with anti-estrogenic properties and omega-3 fatty acids (ALA) that may reduce inflammation. Cancer relevance: In one RCT, flaxseed reduced proliferation in prostate tumors prior to surgery[^9]. 10. Mebendazole Mechanism: Disrupts tubulin polymerization, induces mitotic arrest, downregulates Bcl-2, and inhibits angiogenesis (VEGFR2). Cancer relevance: Shows preclinical efficacy in glioblastoma, colon, and lung cancers[^10]. 11. Ivermectin Mechanism: Inhibits importin α/β (nuclear transport), downregulates STAT3/NF-κB, causes ROS buildup, induces apoptosis, and modulates tumor immunity via P2X4/P2X7. Cancer relevance: Demonstrates anti-tumor activity in breast, leukemia, glioma, and prostate models[^11][^12]. 🧩 Why These Agents Matter These compounds are unlikely to be curative alone. Their value lies in multi-targeted modulation of the tumor environment, metabolic stress, immune activity, and cell survival. Importantly, many have favorable safety profiles, long histories of use, and low cost — making them attractive in both resource-limited settings and experimental adjunctive protocols. Emerging interest has also turned toward repurposed antiparasitic agents like mebendazole and ivermectin, which exhibit multi-pathway anticancer activity, including microtubule disruption, apoptosis induction, immune modulation, and transcriptional interference — a reminder that powerful anti-cancer tools may already exist outside of oncology. ⚠️ Limitations and Cautions Not FDA-approved for cancer. These agents are investigational in this context. Evidence levels vary. Some have human trial data (e.g., aspirin, melatonin, metformin); others rely on preclinical models. Interactions possible. Always discuss use with an oncologist, especially during active treatment. 🔄 Toward a Smarter Future Platforms like CancerCrowdsource.org are enabling patients and clinicians to document real-world experiences with adjunctive regimens like this. Over time, this could allow us to identify which combinations work best, in which cancers, and under what conditions — moving us closer to evidence-based integrative oncology built from the bottom up. 📚 Endnotes [^1]: Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014;14(5):342–357. [^2]: Aggarwal BB, et al. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1–75. [^3]: Ripps H, Shen W. Review: taurine: a “very essential” amino acid. Mol Vis. 2012;18:2673–2686. [^4]: Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013;19(2):151–162. [^5]: Seely D, et al. Melatonin as adjuvant cancer care: a systematic review and meta-analysis. Integr Cancer Ther. 2012;11(4):293–303. [^6]: Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res. 2010;3(9):1060–1065. [^7]: Rothwell PM, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. Lancet. 2011;377(9759):31–41. [^8]: Pantuck AJ, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation. Clin Cancer Res. 2006;12(13):4018–4026. [^9]: Demark-Wahnefried W, et al. Flaxseed supplementation reduces prostate cancer proliferation rates. Cancer Epidemiol Biomarkers Prev. 2008;17(12):3577–3587. [^10]: Nygren P, Larsson R. Drug repurposing: mebendazole as a cancer therapeutic. Expert Opin Investig Drugs. 2014;23(1):105–115. [^11]: Lehrer S, Rheinstein PH. Ivermectin and cancer. Front Pharmacol. 2020;11:626718. [^12]: Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317–331.