Where cancer diagnoses continue to climb, projected to surge by 47% globally by 2040, according to the World Health Organization, it's refreshing to spotlight solutions that don't come from billion-dollar pharmaceutical pipelines. Enter the realm of natural compounds: plant-derived molecules that have been quietly amassing evidence of their anti-cancer prowess for decades, but especially since 2019.

A landmark 2025 review in Chinese Medicine, titled "Natural anti-cancer products: insights from herbal medicine," sifts through over 1,100 studies to spotlight 12 such compounds. These aren't fringe remedies; they're backed by rigorous preclinical data from cell lines, animal models (like mouse xenografts and zebrafish), and omics analyses (transcriptomics, proteomics, metabolomics). They consistently target cancer's "core survival pathways," think apoptosis (programmed cell death), immune evasion, metabolic rewiring, angiogenesis (tumor blood supply), and metastasis, often with fewer side effects than synthetic drugs.

This isn't about ditching conventional treatments; it's about synergy. Many of these compounds show promise in reversing drug resistance (e.g., by downregulating P-gp pumps) and enhancing chemo or immunotherapy. And here's the kicker: several are already in human trials, from Phase I safety checks to Phase III efficacy battles.

The 12 Compounds: A Hit List for Tumour Pathways

The review identifies these 12 as "repeatedly potent" across diverse cancers (breast, lung, prostate, colorectal, and more). They don't just poke at one weak spot; they disrupt multiple hallmarks of cancer, as outlined by Hanahan and Weinberg (link below). Below, we've compiled a table summarising their sources, key mechanisms (from the review and cross-referenced studies), and evidence strength. Preclinical hits are strong; clinical data varies but is growing.

Compound

Natural Source

Core Mechanisms (Key Pathways Targeted)

Evidence Highlights (Preclinical/Clinical)

Apigenin

Chamomile, parsley

↓ PD-L1 (immune detection), ↓ PI3K/AKT/EGFR/ERK (growth signals), ↓ NF-κB/MMP-2/9 (invasion), ↑ apoptosis/autophagy/ferroptosis, ↓ MDR1/P-gp (drug resistance)

Strong in vitro/in vivo (e.g., breast/lung xenografts); Phase I trials ongoing for bioavailability in prostate cancer.

Artemisinin

Sweet wormwood (Artemisia annua)

↑ ROS/lipid peroxidation (oxidative stress), anti-angiogenic (↓ VEGF), ↓ vimentin/N-cadherin (migration), ↓ STAT3/AKT/HSP90 (resistance)

Potent in animal models (e.g., colorectal xenografts); Phase II trials show safety in breast cancer (200 mg/day oral, well-tolerated).

Berberine

Goldenseal, barberry

↓ PI3K/AKT/HER2/TGF-β (growth), ↓ NF-κB (inflammation), ↓ P-gp/MRP1/NRF2/PD-L1 (resistance/evasion), ↓ MMP-2/9 (metastasis)

Broad in vivo efficacy (e.g., liver tumours); Early Phase II for colorectal adjunct therapy.

Curcumin

Turmeric root

↑ apoptosis/autophagy/ferroptosis, ↓ NF-κB/STAT3 (inflammation), ↓ VEGF (angiogenesis), ↓ P-gp/BCRP (resistance), ↓ Twist1/MMP-9/EMT (invasion)

Over 20 Phase I/II trials; Reduces Ki-67 proliferation in colorectal (5% drop at 1g/day); Synergistic with docetaxel in breast cancer.

Emodin

Rhubarb, Japanese knotweed

↓ Wnt/β-catenin/STAT3/NF-κB (communication), ↑ necroptosis/ferroptosis, ↓ GLUT1 (metabolism), ↓ MMP-2/9 (spread), ↓ P-gp/GST (resistance)

Effective in lung/prostate xenografts; Preclinical, but Phase I analogues in pipeline for skin cancers.

EGCG

Green tea catechins

↓ PI3K/AKT/mTOR (growth), ↑ Bax/Bcl-2 shift (apoptosis), ↓ STAT3 (inflammation), ↓ MMP-2/9/VEGF (invasion/angiogenesis), ↓ P-gp (resistance)

Human trials show ↓ PSA in prostate (600 mg/day); Phase II for lung cancer prevention.

Ginsenosides

Ginseng root

↓ EMT/MMP (metastasis), ↓ STAT3 (immune), ↑ caspase (apoptosis), ↑ p53/PTEN (regulation); Gut microbiota modulation

Phase II/III in NSCLC (Rg3 enhances chemo response, ↑ survival); Improves fatigue/QoL in breast cancer.

Icariin/Icaritin

Horny goat weed (Epimedium)

↑ CD8+ T/CXCL9/10 (immune), ↓ PD-L1 (evasion), ↓ PI3K/AKT (growth), ↓ P-gp/MRP1 (resistance), ↑ E-cadherin (adhesion)

Phase III for HCC (vs. sorafenib; ↑ OS to 179 days); Phase II combo with gem/nab-paclitaxel in pancreatic (promising PFS).

Resveratrol

Grapes, berries, red wine

↑ p53 (protective genes), ↓ NF-κB (inflammation), ↓ vimentin/EMT (invasion), ↑ apoptosis/autophagy/ferroptosis; Synergy with chemo

Phase I/II in colorectal (↓ Ki-67 5% at 1g/day); ↑ apoptosis in hepatic mets (5g/day SRT501); Mixed in advanced cancers.

Silibinin

Milk thistle seeds

↓ mTOR/STAT3 (growth), anti-angiogenic, ↓ Wnt/β-catenin (spread), mitochondrial support, ↓ PD-L1

Phase I/II in prostate (high-dose oral safe, ↓ proliferation); Ongoing for NMSC prevention.

Triptolide

Thunder god vine

Nanomolar potency; ↓ NF-κB/STAT3/AKT/mTOR (promotion), ↓ PD-L1/CD47 (evasion), ↑ apoptosis/cell-cycle arrest

Preclinical standout (e.g., pancreatic xenografts); Early Phase I for safety in solid tumors.

Ursolic Acid

Apples, basil, rosemary

↑ p53/ROS (death), ↓ AKT/mTOR (growth), ↓ CXCL12/FN1 (metastasis), ↓ resistance; ↑ ferroptosis via NRF2 suppression

Strong in skin/lung models; Phase I topical for prostate chemoprevention.

Sources: 2025 Chinese Medicine review ; NCI PDQ summaries; ClinicalTrials.gov (as of Nov 2025).

Mechanisms: Hacking Cancer's Code, One Pathway at a Time

Cancer thrives on chaos: unchecked growth (PI3K/AKT/mTOR), sneaky immune hiding (PD-L1 upregulation), blood vessel hijacking (VEGF), and wanderlust (EMT via MMPs/Twist1). These compounds? They're like multi-tool hackers. Take curcumin: It slams NF-κB (inflammation's master switch) and STAT3 (survival signals), while flipping ferroptosis, an iron-dependent cell death that tumours hate but healthy cells shrug off. Artemisinin's ROS burst mimics iron-overloaded cancer cells exploding from within, sparing normal ones low in iron.

Preclinical gold: In zebrafish metastasis models, berberine slashed MMP-9 by 70%, curbing spread. Omics data? Transcriptomics shows EGCG rewiring 200+ genes in breast xenografts toward apoptosis. Multi-omics in the review reveal metabolic sabotage, e.g., emodin's GLUT1 knockdown starves glycolytic tumours. Resistance reversal is huge: 80% of studies post-2019 show these compounds downregulating efflux pumps like P-gp, making chemo hit harder.

But why natural? Pharma drugs often mono-target, breeding resistance. These polypharmics hit 5–10 pathways, mimicking the redundancy of evolution-tested plants. Downside? Bioavailability, curcumin absorbs poorly (use piperine-black pepper combo). Enter nano-formulations: Recent trials boost EGCG uptake 10x.

From Bench to Bedside: Clinical Trials That Matter

The review flags preclinical dominance, but humans aren't mice. Good news: 2025 sees acceleration. Icaritin's Phase III in hepatocellular carcinoma (HCC) beat sorafenib's OS (179 vs. 171 days), with Phase II pancreatic combos showing "promising" PFS. Ginsenosides (Rg3) in Phase II/III NSCLC: 20–30% ↑ response rates with chemo, less toxicity. Curcumin's meta-analysis (21 trials, 2010–2020): 16/21 showed efficacy in leukemia, myeloma, prostate; e.g., Phase I breast trial with docetaxel halved tumor markers.

Artemisinin derivatives shine in repurposing: Phase II breast (artesunate 200 mg/day) extended PFS without added toxicity; ongoing for colorectal. Resveratrol's Phase II colorectal: 5g/day SRT501 ↑ cleaved caspase-3 (apoptosis marker) in liver mets. Silibinin's Phase I/II prostate: High-dose (13g/day) safe, ↓ Ki-67 by 20%. Even triptolide's nanomolar punch enters Phase I for solid tumours.

Challenges? Small cohorts, bioavailability tweaks needed. But safety? Good; mild GI upset at worst, vs. chemo's carnage. Ongoing: NCI's curcumin PDQ lists 15+ active trials; EU's Horizon funds artemisinin combos.

Why the Slow Roll? And What's Next?

Big Pharma's grip: Patents favour synthetics; naturals are "unpatentable" (though formulations like SRT501 skirt this). Funding bias: 90% of oncology trials are pharma-backed. Yet, rising rates (1 in 2 lifetime risk) demand alternatives. These compounds? Affordable (e.g., turmeric at $0.10/day), accessible, and culturally rooted, think TCM's 2,000-year anti-cancer lore.

Prospect? Explosive. 2025 trials target combos: Icaritin + PD-1 inhibitors for HCC; EGCG + radiation for lung. Gut microbiome angle: Ginsenosides reshape tumour-friendly bugs. Data screams potential—1,100+ studies aren't noise. We're at the inflection: From "promising adjunct" to "standard care"?

Bottom line: These 12 aren't cures, but they're good co-pilots. Consult doctors, source pure (e.g., organic turmeric), and dose smart (e.g., 500mg curcumin + piperine). Nature's not naïve, it's been outsmarting cancer longer than we've had labs.

https://www.thefocalpoints.com/p/over-1100-studies-reveal-12-natural