Piperlongumine (Piplartine)

Alkaloid pro-oxidant: ROS/GSTP1 ↑/↓ → apoptosis ↑; preclinical chemo-sensitizer in H&N/colorectal/breast/ovarian; retracted landmark but confirmed.

← All agents

Human-reviewed · How we review →

AI extractedhuman reviewedsources checkedretractions suppressed

🔬⭐⭐ Preclinical — Broad mechanistic and xenograft activity; lacks human therapeutic trials; early landmark paper retracted, but independent confirmation exists.PiplartinePL

Forms: Pure compound capsules (5-20 mg for research) · Long pepper extract (standardized to 5-10% PL)

Educational only, not medical advice. OncoForge makes no claim that Piperlongumine (Piplartine) treats, prevents, or cures any condition, beyond what the linked studies show. Evidence levels vary; effects may not translate to people, and some compounds can cause harm. Always coordinate with your oncology team.

Key Takeaway

Tumor-biased pro-oxidant that inhibits GSTP1 and perturbs thiol systems to push cancer cells past their oxidative limit, triggering apoptosis and chemosensitization in models. Promising preclinical breadth, but no therapeutic human trials to date.

Evidence at a glance

Tier 1 · labHead & NeckColorectalBreastOvarian

Post-retraction preclinical robust (xenografts, synergy); no oncology trials; PK/safety in vitro strong; PXR complexity noted.

How it may work

Piperlongumine elevates ROS and impairs antioxidant defenses by inhibiting GSTP1 and affecting thioredoxin-linked pathways, activating JNK/MAPK, cleaving caspases, and inducing apoptosis (and sometimes autophagy). It suppresses NF-κB/STAT3/PI3K-Akt signaling, reduces migration/invasion, and synergizes with platinums and other cytotoxics in xenografts. Note: the influential 2011 report was retracted in 2018, though independent studies continue to show ROS-mediated anticancer activity.

Targets & pathways

Curated mechanistic targets reported for this agent — how it may act on cells, not proof of a clinical effect.

ROS↑Thiol perturbation and GSTP1 inhibition
GSTP1↓Direct enzyme blockade
Apoptosis↑JNK/MAPK → caspase activation
NF-κB/STAT3↓Survival signaling suppression
Chemo-Sensitizer↑Synergy with platinums via redox

ROSGSTP1ApoptosisChemo-Sensitizer

Often studied / combined with

Combinations reported in the literature, not a protocol or a recommendation.

Cisplatin: Tumor regression in HNSCC xenografts.
Auranofin: Thiol dual-hit in breast cancer lines.
Curcumin: Additive ROS/NF-κB in colorectal models.
Resveratrol: Co-suppressed STAT3 in head & neck.

Overlapping mechanisms

ROS: Overlaps pro-oxidants (e.g., elesclomol); oxidative fatigue risk.
GSTP1: Redundant with telmisartan; monitor detox capacity.

Safety & interactions

Severity and how well-established each signal is are shown separately. Verify everything with your oncologist or pharmacist — absence here does not mean safe.

Risk categories

Oxidative ToxicityHepatotoxicityPregnancy Avoid

Potential interactions

antioxidantsCautionModerateTheoreticalMay blunt ROS-dependent effects (e.g., NAC).
chemo (platinums)SynergizeLowTheoreticalEnhanced cytotoxicity via thiol stress.
CisplatinSynergizeLowTheoreticalImproved response in HNSCC xenografts.

Timing

With-meal: Improves GI tolerance.
BID: Short-term cycles to avoid induction.

References

Research

No published studies for Piperlongumine (Piplartine) yet

New studies appear here once they’ve been reviewed. Browse all studies.

Dose: as studied, not a recommendation

These are doses as studied or reported, never a recommendation. The right amount of Piperlongumine (Piplartine) depends on you, your other medicines, and your situation; decide it with your oncology team and pharmacist, not from a web page.

Ranges seen in adjunct / practice use: 5–20 mg/day (po) divided BID; research-only; with food, Preclinical 5-10 mg/kg; human extrapolated 10-20 mg/day short-term; no established oncology dosing—monitor oxidative markers..

Trials studying Piperlongumine (Piplartine)

No actively-recruiting trials matched right now. Recruiting is not the same as proven. Search ClinicalTrials.gov →

Inclusion here is not an endorsement. OncoForge makes no claim beyond what the linked studies show. Discuss anything on this page with your oncology team before acting on it.

← All agents · Research Radar